Although most thyroid cancers are treated and cured successfully there are still 30% who recur after many years. This will eventually progress and at this point may become incurable with treatment options including complex and high risk surgery. The overall efficacy of systemic treatment in advanced thyroid cancer has a good initial response in most patients but not all. The study will collect tissues and blood samples for various protein analysis, nucleic acid extraction and live cell analysis in order to try and detect the presence of plasma ctDNA at baseline of eligible patients.

The treatment decisions are based on relying on radiological parameters such as using the RECIST criteria and measuring the rise in certain serum tumour biomarkers. However, the disadvantage of this is that this method can take many months to detect a change in disease volume. An improved understanding of genetics and cancer and potential gene sequencing can help achieve personalised treatment for patients. However, there are many questions and issues that still need to be answered and require urgent attention before being able to achieve optimate patient stratification. We need to identify better tumour biomarkers to detect disease progression, show real time response to treatment and understand why tumours evolve to becoming more aggressive. This study hopes to address these issues by proposing a multicentre prospective study to investigate the presence and role of ctDNA in advanced thyroid cancer including differentiated thyroid cancer , medullary thyroid cancer and Anaplastic Thyroid Cancer.

Inclusion Criteria:

• Age 18 years or older. (all cohorts)
• Patients diagnosed with radioiodine refractory differentiated thyroid carcinoma (RR-DTC) under surveillance. (cohort 1)
• Patients with newly diagnosed resectable locally advanced medullary thyroid cancer Or Patients with newly diagnosed metastatic medullary thyroid cancer for surveillance Or Patients with locally advanced or metastatic medullary thyroid cancer on surveillance (cohort 2)
• Patients with RR-DTC starting systemic therapy Or Patients with RR-DTC on systemic therapy Or Patients with MTC starting systemic therapy Or Patients with MTC on systemic therapy (cohort 3)
• Patients with newly diagnosed anaplastic thyroid cancer (cohort 4)
• Availability of tissue from one archival diagnostic tumour tissue block or be willing to have biopsy of accessible disease (all cohorts)
• Patients must be willing to undergo standard monitoring and treatment as recommended by their clinical team (all cohorts)
• Ability to give informed consent for biological sample collection. (all cohorts)

Exclusion Criteria:

• Previous or concurrent illness, which in the investigator's opinion would interfere with collection of the complete sample collection
• Any invasive malignancy within previous 5 years (other than non-melanomatous skin carcinoma or carcinoma in situ)
• Pregnancy

Patients with thyroid cancer