Biomarkers in Thyroid Cancer
Research type
Research Study
Full title
Identification of Molecular Biomarkers for Thyroid cancer
IRAS ID
173647
Contact name
Katie L Newbold
Contact email
Sponsor organisation
The Royal Marsden NHS Foundation Trust
Duration of Study in the UK
2 years, 11 months, 31 days
Research summary
Summary of Research
Thyroid cancer is the most common endocrine tumour (90% differentiated thyroid cancer (DTC) 5% anaplastic carcinoma, 5% Medullary thyroid cancer (MTC)).
DTC is managed with surgical excision, then radioiodide ablation. Five to 15% of DTC will however become refractory to radioiodide. In this setting multi-targeted kinase inhibitors (KIs) have shown activity. MTC is managed surgically. RAI is not useful in MTC. KIs are also used in advanced and metastatic MTC.
In both DTC and MTC there remains a question as to when to initiate KI therapy. Current measures of disease progression are radiological (RECIST) or biochemical, thyroglobulin (Tg) in DTC and calcitonin (Ct) and carcinoembryonic antigen (CEA) in MTC. These biomarkers are a blunt tool and there is a need for a more informative marker of both rate of disease progression and predictive of the individual tumour response to treatment. A better understanding of the tumour molecular profile may also help inform treatment choice.
Tumour DNA can be noninvasively assessed in the plasma: cell-free circulating tumour DNA (ctDNA). In DTC there is a need for a better indicator of response to treatment in view of the lack of disease–specificity of Tg. In both DTC and MTC there is a need for a method of assessing early recurrence and, in advanced disease, the mechanisms of disease. ctDNA may provide temporal measurements of tumor burden and identify specific mutations that arise during therapy.
This is a two part study; part A proposes to collect plasma samples to examine how ctDNA markers correlate with detection of recurrent disease, response to therapy, clinical outcome and pathological data. Part B aims to use tissue obtained from biopsies of primary or recurrent disease to establish cell lines and tumour explants to further investigate the biology of thyroid cancer in the pre-clinical setting.Summary of Results
Through multi-mutational analysis of plasma, ctDNA was detected in the majority (76%) of patients with advanced thyroid
cancer.
The median ctDNA concentrations were significantly higher (p=0.005) in patients with progressive disease on imaging
compared to stable or responding disease.
A change in ctDNA concentration predicted radiological findings.
Conclusions:
ctDNA measurement may offer superiority over conventional markers in several scenarios:
1) earlier detection of progression in medullary thyroid cancer
2) as an alternative biomarker when conventional markers are not available for example when antibodies interfere with
the thyroglobulin levels
3) more rapid assessment of the disease status in response to targeted therapies, thereby potentially allowing prompter
discontinuation of futile therapies or guiding a switch to a more effective treatmentREC name
West of Scotland REC 3
REC reference
15/WS/0148
Date of REC Opinion
2 Sep 2015
REC opinion
Further Information Favourable Opinion