Detection of Circulating Tumour Cells in Thyroid Cancer (CircuiTT)
Research type
Research Study
Full title
Feasibility of detection and enumeration of Circulating Tumour Cells in Thyroid Cancer using the Veridex LLC (Cell-Search) and the ImageStreamX Mark II (Amnis) flow cytometry methods – A Newcastle-Manchester joint pilot study (Acronym:—CircuiTT)
IRAS ID
192989
Contact name
Peter Truran
Contact email
Sponsor organisation
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Clinicaltrials.gov Identifier
BH140883, BH reference
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Summary of Research
This is a pilot study with the primary aim of assessing the feasibility of detecting circulating tumour cells (CTCs) in the bloodstream of patients with thyroid cancer. The modern Veridex and ImageStreamX methods will be used and compared in this study for the detection of CTCs, as little work has been carried out to detect CTCs in thyroid cancer using modern detection methods. There are significant limitations to current tests (including blood thyroglobulin analysis, ultrasound and radioiodine scans) for assessing disease status and prognosis for thyroid cancer, including sensitivity and reliability of cancer detection in some cases. Hence, we hope that this study will lead to further studies to confirm the clinical usefulness of CTC detection, in comparison with current tests, in the diagnosis, prognosis and monitoring of thyroid cancer.
The study will involve taking blood for CTC detection from patients at 3 time points [pre-surgery , approximately 2-3 weeks post surgery (pre-radioiodine ablation) and 5-7 months post radioiodine ablation] from patients with thyroid cancer at a hospital clinic visit.
The participant population will include patient with locally advanced or high risk differentiated thyroid cancer.
Planned sample size is 30 participants.
The study is planned to take 2 years from start of recruitment to final data analysis.Summary of Results
This was a pilot study conducted to see if tumour cells circulating in blood (known as circulating tumour cells CTCs) could be detected in patients with thyroid cancer, as many studies have suggested that high CTC load is directly associated with worse prognosis and increased recurrence risk in most solid cancers, but minimal work has been carried out in thyroid cancer. Two methods were used to identify CTCs, one called CellSearch and the other called Imagestream. Samples were taken at 3 timepoints for each participant (pre-surgery, post 2 weeks after surgery but pre-radioactive iodine ablation and 5-12 months post-radioiodine ablation (RAI)) to facilitate investigations into whether CTCs may be clinically useful as in the diagnosis or monitoring of thyroid disease in comparison to standard methods of thyroid cancer detection.
At least one sample was received from 28 out of 30 patients recruited, for blood CTC analysis. 3 of these patients had benign tumours and 25 patients had confirmed thyroid cancer. Of the 25 thyroid cancer patients, 18 provided 3 samples for analysis by CellSearch and 20 provided 3 samples for analysis by ImageStream.
By CellSearch CTCs were only detected in 2 out of 25 samples at baseline, none in 23 samples post-surgery and in 2 out of 20 samples after RAI. A far greater number of CTCs were detected using the Imagestram method. By ImageStream CTC like objects were identified in 19 of 28 sample including 17 of 23 samples post-surgery, and in 10 of 20 samples after RAI. CellSearch and Imagestream use different criteria for identifying CTCs, which may account for the lack of concordance when comparing CTC detection between the two methods.
No association was detected between the presence of CTCs and cancer, as all three of the baseline samples from people with benign thyroid disease had CTCs detected by Imagestream, although CTCs in these samples were not detected by the CellSearch method.
In the 25 patients with confirmed disease there was an apparent decrease in CTCs, using the ImageStream method, over the course of therapy. The three patients with confirmed disease after therapy all had detectable CTCs in the post RAI sample compared with 7 out of 17 with no detectable disease after therapy, though this was not statistically significant.
In summary, the CellSearch method, for identifying CTCs, relies on cells expressing a molecule called EpCAM, which many cancer types express. It is possible EpCAM may not be present in the majority of thyroid CTCs, hence identification of low CTC numbers by CellSearch compared with the ImageSteam method which does rely on EpCAM expression for CTC identification. However, this study also shows that the ImageStream method used is not specific enough to detect CTCs in patients with suspected thyroid cancer, as this method also detected CTCs in the 3 benign thyroid tumours, hence more specific criteria are required for the detection of thyroid CTCs.
REC name
London - Central Research Ethics Committee
REC reference
16/LO/1183
Date of REC Opinion
16 Jun 2016
REC opinion
Favourable Opinion