18F-Fluorocholine PET/CT in Medullary Thyroid Cancer

Diagnostic Value of 18F-Fluorocholine PET/CT for the Detection of Medullary Thyroid Cancer

To assess the diagnostic accuracy of 18F-Fluorocholine PET/CT for the detection of medullary thyroid cancer in patients with primary and recurrent disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Medullary Thyroid Cancer
• Intervention / Treatment: Diagnostic test: 18F-fluorocholine PET/CT

Detailed Description

Medullary thyroid cancer (MTC) is a relatively rare type of cancer that represents up to 10% of all primary thyroid cancers. It is a neuroendocrine tumour derived from parafollicular C-cells of the thyroid. It occurs either sporadically or in a hereditary form as a component of the type 2 multiple endocrine neoplasia (MEN) syndromes, MEN2A and MEN2B, and the related syndrome, familial MTC (FMTC).

Currently, the diagnosis of MTC is suspected based on the results of fine-needle aspiration (FNA) cytology, immunohistochemical analysis and elevated laboratory values of tumour markers calcitonin (Ctn) and carcinoembryonic antigen (CEA). According to the 2015 ATA guidelines, the preoperative imaging workup in all patients should include ultrasound examination of the neck; in selected patients, contrast-enhanced CT of the neck and chest, three-phase contrast-enhanced multi-detector liver CT, or contrast-enhanced MRI of the liver, and axial MRI and bone scintigraphy is also recommended. The curative therapy of choice is surgical removal of the tumour and/or metastases.

Nodal metastases are detected in 35-50% and distal metastases in about 15% of patients with primary MTC. Even with currently recommended diagnostic imaging techniques, about 50% of patients have persistent/recurrent disease after surgical treatment. This implies that currently available diagnostic imaging studies are suboptimal for accurate disease staging. New hybrid molecular imaging techniques based on SPECT/CT and especially PET/CT could improve disease detection by visualising pathophysiological processes in vivo. The most studied PET radiopharmaceutical for MTC imaging to date has been 18F-FDOPA, with recent studies focusing also on somatostatin receptor imaging using 68Ga-DOTATATE/TOC/NOC radiotracers.

18F-fluorocholine is a structural analogue of choline. It accumulates in cells with active membrane synthesis and overexpressed intracellular signal transduction, processes that are overactive in benign and malignant neoplasms. 18F-fluorocholine is currently primarily used for prostate cancer imaging. In contrast to radiotracers such as18F-fluorodeoxyglucose (18F-FDG), it is also taken up by well-differentiated neoplasms in which 18F-FDG uptake is unreliable. Similarly to 18F-FDG, 18F-fluorocholine is also known to accumulate in inflamed and infected tissue. However, this limitation could be overcome by performing multi-time-point imaging and using basic kinetic analysis. The working hypothesis is that 18F-fluorocholine might be efficiently taken up by primary MTC tumour as well as loco-regional and distant metastases.

The aim of the trial is to investigate the diagnostic accuracy of 18F-fluorocholine PET/CT in comparison to existing imaging modalities (US, CT and MRI).

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Department for nuclear medicine, University medical centre Ljubljana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with medullary thyroid cancer treated at the Institute of Oncology Ljubljana.

Description

Inclusion Criteria:

• Patients with medullary thyroid cancer (sporadic or hereditary form).
• Patients with newly diagnosed MTC for primary staging (based on fine needle aspiration cytology results).
• Patients with suspicion of MTC recurrence for re-staging (based on biochemical, conventional imaging or clinical examination).
• Patients with metastatic MTC on systemic therapy for disease activity assessment.

Exclusion Criteria:

• Pregnancy.
• Patient with any PET/CT-scan exam contraindication (eg. severe claustrophobia).

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MTC 18F-fluorocholine PET/CT; Patients with medullary thyroid cancer imaged using 18F-fluorocholine PET/CT.	Diagnostic test: 18F-fluorocholine PET/CT; 18F-fluorocholine PET/CT imaging of the neck, mediastinum and whole body.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy in primary medullary thyroid cancer	Ability to detect primary medullary thyroid cancer (primary, nodal and metastatic lesions) in correlation with histopathological and/or conventional imaging data.	1 month
Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy in recurrent medullary thyroid cancer	Ability to detect recurrent medullary thyroid cancer (nodal and distant metastatic lesions) in correlation with histopathological and/or conventional imaging data.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival analysis based on the initial PET/CT examination	Survival analysis of the time to disease progression or disease recurrence after the initial PET/CT examination.	5 years
Biochemical/clinical outcome - Ctn levels	Normalization/stable elevation/increasing levels of serum Ctn.	5 years
Biochemical/clinical outcome - CEA levels	Normalization/stable elevation/increasing levels of serum CEA.	5 years
Correlation between tumour metabolic activity and biochemical and histological markers	Correlation of tumour metabolic activity with biochemical serum marker levels (Ctn, CEA) and tumour metabolic activity and histological quantitative indexes (eg Ki-67).	1 month
Modification rate of patient's surgical and medical care after 18F-fluorocholine PET/CT	Rate of patients whose management was modified based on the PET/CT imaging findings.	5 years
Basic kinetic analysis of metabolic activity in the primary tumour, nodal and distant metastases.	Ability to differentiate benign and malignant lesions using multiple-time-point imaging.	3 months

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Collaborators: Institute of Oncology Ljubljana

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2014
• Primary Completion (Anticipated): March 3, 2021
• Study Completion (Anticipated): September 3, 2024

Study Registration Dates

• First Submitted: August 20, 2018
• First Submitted That Met QC Criteria: August 20, 2018
• First Posted (Actual): August 22, 2018

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: imaging; PET/CT; PET; medullary thyroid cancer; hybrid-imaging; 18F-choline; 18F-fluorocholine
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Thyroid Diseases; Thyroid Neoplasms; Carcinoma, Neuroendocrine
• Other Study ID Numbers: 92/08/14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No