ctDNA guided diagnosis and management of gastrointestinal cancers
Thesis or Dissertation
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Gastrointestinal (GI) cancers including pancreatic (PC), biliary tract (BTC) and colorectal cancers (CRC) rely on a tissue biopsy through invasive procedures such as endoscopies and colonoscopies. Timely diagnosis of these cancers is critical to facilitate access to potentially life prolonging treatments. The COVID-19 pandemic highlighted the fragility of the current invasive diagnostic pathways for upper and lower GI cancers. In the UK, there was a reduction in capacity of colonoscopies and endoscopies as resources were re-directed to focus on the pandemic. There is a high unmet need for non-invasive biomarkers to support a diagnosis of cancer in patients with suspected PC, BTC and CRC. My thesis focuses on the following work I have completed: - Designing and reporting on a prospective study of circulating tumour DNA (ctDNA) to support a diagnosis of PC/BTC and to triage colonoscopies in patients with suspected CRC - Designing and implementing a prospective, real-world programme assessing ctDNA as a supportive diagnostic biomarker in patients with suspected advanced PC and BTC I developed and reported on the PREVAIL ctDNA study, assessing the use of ctDNA as a supportive diagnostic tool in patients with suspected cancer across multiple tumour types including PC, BTC and CRC. This is the first prospective study assessing the use of a multi-gene ctDNA assay, in a tumour-agnostic approach to support a diagnosis of PC/BTC and inform treatment decisions. My thesis reports on the rationale, design, and final results from the PC, BTC and CRC cohorts of the PREVAIL ctDNA study. Following the PREVAIL ctDNA study, I developed and implemented a larger, real-world programme assessing ctDNA as a supportive diagnostic biomarker in patients with suspected advanced PC/BTC (the ACCESS programme). The programme is actively recruiting at the time of writing my thesis. My final chapter will describe the rationale, design and interim results from the ACCESS programme.
GI Clinical Trials
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Institute of Cancer Research (University Of London)