Dr Miles Levy, consultant endocrinologist, Leicester

 

Research project: The use of circulating cell-free tumour-derived DNA (ctDNA) in the diagnosis and monitoring of thyroid cancer

Recent advances in the diagnosis and management of thyroid cancer have seen the five-year survival rate rise to 98%. However, thyroid cancer recurs in up to one in five patients. Currently, thyroglobulin (Tg)  and calcitonin are the two most commonly used biomarkers for detecting recurrence of papillary and medullary thyroid cancer respectively. However, they are imperfect. So there is a need for more sensitive and specific testing (biomarkers) for thyroid cancer.

This study through our 2022 BTF Research Award investigated the use of circulating cell-free tumour DNA (ctDNA) in the diagnosis and monitoring of thyroid cancer. It built on the pioneering work already done at the Leicester Cancer Research Centre using ctDNA in the diagnosis and treatment of lung, breast and bowel cancer.

The researchers studied the DNA of each person’s thyroid cancer to look for mutations that have occurred in their cancer. Using these findings, researchers planned to design a bespoke blood test for each patient to look for this mutation-containing ctDNA in their blood. They then tracked the levels over time to see whether this ‘liquid biopsy’ can detect recurrence of thyroid cancer. It has the potential to detect worsening cancer before it is shown on the scans and to guide treatment choices, individualised to the patient.

Final report on study

What was the background to your study?

Thyroid cancers are the commonest tumours of the endocrine system. Although most people survive for more than 5 years after treatment, around 30% may face a recurrence. The current methods for diagnosis and monitoring involve biomarkers, imaging, and biopsies, but they have limitations. This study explores a novel way of monitoring thyroid cancer by the use of liquid biopsies, which are non-invasive tests that analyse components of blood to detect genetic alteration in those tiny pieces of DNA that break away from cancer cells and float in the bloodstream. The fragments of tumour DNA in blood termed circulating tumour-derived DNA (ctDNA).

What was the aim of your research?

The goal of the study is to see if ctDNA can be found in the blood of thyroid cancer patients and if it can act as a marker for the disease over time. The study involves collecting tumour tissue and blood samples from patients with various types of thyroid cancer. Different tests, including while exome sequencing digital droplet PCR and shallow whole-exome sequencing, are performed on these samples of tumours and blood to detect specific genetic changes associated with cancer.

Which groups of patients were involved in the study?

Adult patients with confirmed diagnosis of thyroid cancer of any type would be eligible for the study. We tried to include patients at different stages of treatment of thyroid cancer to reflect real-life outcome. The study excluded patients under 18 years of age, pregnant and patients with another active cancer.

How did you conduct the research?

Blood tests were collected in special bottles from patients on intervals and were processed to separate the components. Thyroid cancer tissues were also accessed and DNA was separated. DNA from blood cells and thyroid cancer were then sent for genetic testing to find the gene alterations that might have caused thyroid cancer. The identified gene alterations were then searched in patients’ plasma to track cancer activity over time.

What were your findings?

From 23 patients recruited to the study, we identified the presence of positive genetic alterations in certain types of thyroid cancer, such as BRAF^V600E and NRAS^Q61R. We are going to complete genetic testing in all blood samples looking for circulating fragments of DNA containing the gene alterations during follow up. We are also going to compare changes of levels of circulating DNA fragments with traditional cancer markers and imaging results.

What role did the BTF funding play?

The BTF award played key part in covering the cost of research including ordering assays, genetic testing, laboratory costs and consumables.

What are the next steps in your research?

We aim to complete genetic testing on all blood samples and compare the levels of circulating DNA fragments with traditional cancer markers and imaging results.

How would you summarise this project?

This research aims to use ctDNA as a less invasive and more convenient method for monitoring thyroid cancer, potentially improving the accuracy of diagnosis and tracking disease progression over time. The research identified new genetic variants that might be contributing in the development of thyroid cancer. These findings open the doors for future research projects in the genetics of thyroid cancer.

Previous research updates from Dr Levy

Interview with Dr Levy 2022

Progress report July 2023 

Read about past BTF Research Award-funded studies

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