The EDUCATE Study: Early Detection of recUrrence of CAncers of the brain using lateral flow TEsts

In the UK, more than 2,500 people a year die from high-grade gliomas each year, rising to more than 190,000 people globally. The most aggressive of these have only a 12-15 month survival rate, with the tumours invariably recurring after treatment. The resurgence of the tumours is both unpredictable and highly irregular therefore the current 3-6 month MRI scans are often picking up this regrowth too late. The EDUCATE study (Early Detection of recUrrence of CAncers of the brain using lateral flow Tests) seeks to use the science behind work undertaken throughout the pandemic by the team, to develop a lateral flow test which can detect this tumour recurrence at the very early stages and thereby give patients the very best chance at treatment through far earlier intervention. We will do this through the 3 main arms of the EDUCATE study. Firstly, advanced lateral flow test (LFT) development will take place to detect these very early warning signs of recurring gliomas. We will use a range of the most recent technologies to find the smallest amounts of statistically significant biomarkers which can predict this tumour recurrence and offer patients a weekly testing opportunity. These LFTs will then be used as part of our blinded EDUCATE feasibility trial on patients at Sheffield Teaching Hospitals Trust to assess the cross-validation and implementation of this technology in a real-world and clinical setting. Finally, with the data gathered throughout the first two phases of the EDUCATE study, we will be in position to combine our understanding of these predictive biomarkers into a model which can also supplement current MRI scanning. This will add advanced information to the images seen by the clinicians and link that to our metabolic, genomic and transcriptomic data obtained in phases 1 and 2. The EDUCATE study will offer the first opportunity for at-home recurrence testing, dramatically increasing the early detection prospects for brain tumour recurrence with state-of-the-art lateral flow testing, and opening up further opportunities to widen this as a platform technology for cancers of unmet need more widely.

Despite the current clinical paradigm of interval MRI scans every 3-6 months, delays in detecting the recurrence of brain cancer contribute to missed opportunities for life-extending intervention including further surgery and/or pharmacotherapy. Leveraging lessons from the covid-19 pandemic such as regular at home lateral flow testing (LFT) and NICE-approved clinical practice whereby neurosurgeons routinely exploit elevated concentrations of the haem precursor protoporphyrin IX (PpIX) within cancerous cells to provide tumour-specific fluorescence, the proposed studies will develop and validate a lateral flow test for PpIX detection (LFTPpIX) within an easily accessible biofluid to detect early increases in cancer cell burden before these are visible on conventional imaging. The studies will generate pre-clinical and early clinical data supporting LFTPpIX as a novel device empowering patients to perform weekly self-assessment for cancer recurrence using an approach substantially more affordable to the NHS than conventional liquid biopsy. Additionally, the expertise of our newly-established early detection consortium will be applied within further inter-disciplinary approaches to develop an innovation pipeline with focuses on patient-group stratified testing and advanced nanoparticle approaches to support next-generation devices capable of detecting tumour first occurrence to provide a full circle solution for early detection in brain cancer and guide its application to other difficult-to-treat malignancies.