Lisanne de Koster

491 MD and [18F]FDG-PET/CT: complementing techniques or waste of valuable resources? 12 likely a random sample, as no significant differences in failed MD were observed in relation to the age of cytology smears (3 to 6 years old, p=0.25) or between Bethesda classifications (15% failure in Bethesda III versus 9% in Bethesda IV, p=0.25), as well as no differences in results between the patients with successful MD on cytology (n=115) and all with successful MD (n=130). Other potential limitations include the small number of malignant/borderline tumours, limiting the power to detect statistically significant differences in sensitivities between the diagnostics, and the patient selection methods. According to the current Dutch thyroid guidelines, routine FNAC is only recommended for palpable nodules, regardless of their ultrasound pattern with the exception of a simple cyst [467]. This is reflected by the 79% palpable nodules and relatively large nodule size in the current study (Table 1), and may not be fully representative for study populations that define other inclusion criteria. Besides that, there is the possibility of sampling error and imperfections in the morphological histopathological diagnosis as a reference standard [721, 722]. Even though this accurately reflects clinical practice, it may result in a faulty assessment of the tumours’ molecular profile as compared to its [18F]FDG uptake and benign or malignant nature. Finally, a significant number of patients in the current study did not undergo diagnostic surgery, as per protocol in the EfFECTS trial. Although aggressive tumour behaviour becomes less likely as active surveillance continues, an unchanged ultrasound follow-up does not exclude malignancy. Long-term analyses of the trial’s results are scheduled. In conclusion, the current study demonstrated that both MD and [18F]FDG-PET/CT are accurate rule-out tests in ITN when unresected nodules that remain unchanged on ultrasound follow-up are considered benign. The rule-in capacity of both diagnostics is insufficient due to a limited number of mutations with a high rate of malignancy and a high rate of [18F]FDG positive benign nodules. It may vary worldwide which of these diagnostics is considered the most suitable primary test, depending on the local availability of diagnostics, preoperative stratification using ultrasound classification systems, multidisciplinary expertise, and cost-effectiveness considerations. In non-oncocytic ITN, MD and [18F]FDG-PET/CT are complementary, but their combined use should not routinely be recommended as therapeutic consequences are confined. Sequential application of [18F]FDG-PET/ CT may only be considered in case of first-step negative MD to confirm that withholding diagnostic surgery is oncologically safe. In oncocytic ITN, visual [18F]FDG-PET/CT assessment is unable to differentiate between benign and malignant oncocytic tumours. MD including CNA-LOH analysis seems promising and could be considered in oncocytic ITN after further validation studies.

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