Lisanne de Koster

471 MD and [18F]FDG-PET/CT: complementing techniques or waste of valuable resources? 12 Introduction Over the past years, molecular diagnostics (MD) have become increasingly relevant in the preoperative workup of cytologically indeterminate (Bethesda III and IV) thyroid nodules (ITN)[17, 27, 691]. The interpretation and use of finding different molecular alterations including DNA variants, gene fusions and chromosomal copy number alterations (CNA) is based on many contributions in the literature [525, 692-694]. In oncocytic neoplasms, CNA with near-whole genome haploidization with or without subsequent genome doubling is considered to be an important genomic driver [343, 483, 484, 649, 674, 675, 695]. The leading molecular panels test for a wide range of molecular alterations and thereby ensure highly accurate rule-out and rule-in capabilities with test sensitivities ≥92% and specificities ≥38% [490, 696, 697]. Unfortunately, these commercial panels have limited global availability outside the United States, necessitating other diagnostic options for these patients including European initiatives with 7-gene MD panels and molecular imaging using positron emission tomography/ computed tomography (PET/CT) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG)[492, 493, 501]. With a 94% sensitivity, [18F]FDG-PET/CT accurately excludes malignancy in ITN and cost-effectively avoids 40% of futile diagnostic surgeries for benign nodules [28, 501]. The specificity of [18F]FDG-PET/CT is only 40% as many non-cancerous ITN also show increased uptake of [18F]FDG [501]. In the current study, we compared the diagnostic performance of MD and [18F]FDG-PET/CT in ITN and assessed the efficacy of their combined use. In addition, we explored whether specific molecular alterations drive the variability in [18F]FDG uptake among benign thyroid nodules. Material and methods Study design This study included Adult, euthyroid patients with a Bethesda III or IV thyroid nodule who participated in the Efficacy of FDG-PET in Evaluation of Cytological indeterminate Thyroid nodules prior to Surgery (EfFECTS) trial. This prospective, triple-blinded, randomized controlled multicentre trial was performed in eight academic and seven large community hospitals in the Netherlands between July 2015 and December 2019 (Clinicaltrials.gov: NCT02208544, Supplementary Data). At all participating institutions, the diagnosis and management of thyroid nodules was carried out in a multidisciplinary setting by highly experienced physicians and in accordance with the applicable national and international guidelines [17, 467]. Trial inclusion criteria, comprehensive study procedures, and main results were previously published [501]. In short, prior to enrolment in the EfFECTS trial, the Bethesda III (confirmed on two subsequent fine needle aspiration cytology [FNAC]

RkJQdWJsaXNoZXIy MTk4NDMw