FDG-PET/CT in Evaluation of Cytological Indeterminate Thyroid Nodules to Prevent Unnecessary Surgery (EfFECTS) (EfFECTS)

This is an interventional diagnostic trial for Thyroid Nodule focused on measuring Thyroid Nodule, Indeterminate Cytology, FDG-PET/CT, Diagnostic Thyroid Surgery, Efficacy, Cost-Effectiveness, Quality-of-Life, Thyroidectomy Read More

Inclusion Criteria:

1. Documented history of a solitary thyroid nodule or a dominant nodule within multinodular disease, with (US-guided) FNAC performed by a dedicated radiologist or experienced endocrinologist or pathologist, demonstrating an indeterminate cytological examination (i.e. Bethesda category III or IV) according to the local pathologist and confirmed after central review;
2. Scheduled for surgical excision (preferably) within 2 months of the inclusion date;
3. Age ≥ 18 years;
4. Euthyroid state with a serum thyrotropin (TSH) or a free T4 level within the institutional upper and lower limits of normal, measured within 2 months of registration. In case of a suppressed TSH: a negative 123I, 131I or 99mTcO4- scintigraphy must be available ("cold nodule");
5. In patients with multinodular disease and a dominant nodule, the nuclear medicine physician responsible for FDG-PET/CT scan interpretation must determine whether the nodule is likely to be discriminated on FDG-PET/CT imaging prior to enrolment;
6. Willing to participate in all aspects of the study;

Exclusion Criteria:

1. High a priori probability of malignancy:

   • FNAC Bethesda category V or VI during local reading or central review;
   • Prior radiation exposure / radiotherapy to the thyroid;
   • Prior neck surgery or radiation that in the opinion of the PI has disrupted tissue architecture of the thyroid;

   • New unexplained hoarseness, change of voice, stridor or paralysis of a vocal cord;

     • In case a benign reason has been found (e.g. vocal cord edema), the patient is eligible;
   • Thyroid nodule discovered as a FDG-PET positive incidentaloma

   • New cervical lymphadenopathy highly suspicious for malignancy;

     • In case malignancy is excluded, patient is eligible;
   • Previous treatment for thyroid carcinoma or current diagnosis of any other malignancy that is known to metastasize to the thyroid;
   • Known metastases of thyroid carcinoma;

   • Known genetic predisposition for thyroid carcinoma:

     • Familiar Non-Medullary Thyroid Cancer (NMTC)
     • Familiar Papillary Thyroid Cancer (FPTC)
     • Familiar Adenomatoid Polyposis Coli syndrome (FAP, Gardner syndrome, APC-gene mutations on chromosome 5q21)
     • Morbus Cowden (PTEN mutation on chromosome 10q23.3)
     • PTC / nodular thyroid hyperplasia / papillary renal tumours. Linked to locus 1q21.

2. Proven benign disease or insufficient material for a cytological diagnosis:

   • FNAC Bethesda category I or II during local reading or central review
3. Performance of non-routine additional diagnostic tests that alter the patients treatment policy (e.g. mutation analysis on cytology)

4. Inability to undergo randomization:

   • Any patient that will receive thyroid surgery for other reasons (e.g. mechanical or cosmetic complaints).

5. Inability to undergo treatment:

   • Inability to undergo surgery in the opinion of the surgeon / anaesthetist.

6. Contra-indications for FDG-PET/CT:

   • Patient has evidence of infection localized to the neck in the 14 days prior to the FDG-PET/CT scan;
   • Inability to tolerate lying supine for the duration of an FDG-PET/CT examination (~10-15min);
   • Poorly regulated diabetes mellitus (see next item);

   • Hyperglycaemia at time of FDG injection prior to PET/CT (fasting serum glucose >200mg/dL [>11.1 mmol/L]);

     • The use of short-acting insulins within 4 hours of the PET scan is not allowed

   • If female and fertile: signs and symptoms of pregnancy or a positive pregnancy test / breast-feeding;

     • A formal negative pregnancy test is not obligatory

   • (severe) claustrophobia;

     • Low dose benzodiazepines are allowed

7. General contra-indications:

   • Inability to give informed consent;
   • Severe psychiatric disorder;