Brain tumour patients currently receive uniform radiotherapy doses, even though oxygen-starved regions within their tumours are far more resistant to radiation and likely to regrow. This project tests whether oxygen-enhanced MRI can map those hypoxic zones in real time, allowing doctors to target them with higher radiation doses while sparing healthy tissue. High-grade gliomas kill most patients within 14 months, largely because tumour cells infiltrate surrounding brain tissue and hypoxic areas shrug off standard treatment. Current imaging cannot distinguish these resistant pockets, so radiotherapy treats the whole tumour identically. If OE-MRI reliably identifies and tracks hypoxia as patients undergo treatment, clinicians could escalate doses precisely where needed, potentially reducing local recurrence. Success would lay the groundwork for a UK clinical trial testing hypoxia-guided radiotherapy. If that trial confirms benefit, the approach could shift standard practice for the most common malignant brain tumour in adults—not by inventing new drugs, but by making existing radiation work harder where it matters most. The research also establishes OE-MRI protocols that other cancer centres could adopt, improving consistency across the NHS.
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Background High-grade gliomas (HGG) are the most common primary cancerous brain tumours in adults, with an average life expectancy of just 14 months post-treatment. Patients with HGG (pwHGG) often experience debilitating symptoms, and their prognosis is poor due to tumour infiltration into surrounding tissue and resistance linked to low-oxygen (hypoxic) regions. Oxygen-enhanced MRI (OE-MRI) can identify these hypoxic areas, allowing for tailored radiotherapy that delivers higher doses to resistant regions, potentially reducing recurrence and improving survival and quality of life for pwHGG. Research Question This Study aims to determine if OE-MRI can effectively identify and track hypoxic regions within pwHGG and whether this information enhances radiotherapy targeting to improve outcomes. The primary research question is: can OE-MRI effectively identify and monitor hypoxia in pwHGG, facilitating more precise radiotherapy to improve clinical outcomes? Aims and Objectives The research is structured into three main work packages (WPs): WP1: Focuses on implementing OE-MRI at Leeds Cancer Centre (LCC), requiring an overseas research visit, a systematic review of OE-MRI techniques for pwHGG, and optimisation of OE-MRI sequences on the MR-Sim, through testing with healthy volunteers. WP2: Uses OE-MRI to identify hypoxia in pwHGG, visualising changes during treatment through multiple imaging sessions while recording patient details, including recurrences. WP3: Utilises these images to simulate radiation dose escalation in a treatment planning system (TPS) to assess tumour control probability (TCP). Methods The Study will utilise a dedicated MRI for radiotherapy at LCC (MR-Sim). WP1 involves a research visit to learn OE-MRI techniques and optimisation of equipment with healthy volunteers. WP2 involves OE-MR images of pwHGG at different treatment stages - during treatment simulation, midway through radiotherapy, at the end of treatment, and 3-6 months later - monitoring changes in oxygen levels, correlating hypoxia with tumour recurrence. WP3 will create new theoretical radiotherapy treatment plans that escalate doses to hypoxic regions identified by OE-MRI, assessing TCP for potential benefits. Timelines for Delivery WP1 will last approximately six months, beginning with a six-week research visit and a concurrent systematic review. Equipment procurement will start before the fellowship, followed by two months of investigations, including tests with healthy volunteers. WP2 will span 24 months, starting six months into the fellowship with a patient recruitment period of up to 18 months. Initial OE-MR images will be obtained two months after recruitment, followed by staggered imaging throughout treatment. WP3 will overlap with WP2 for up to 18 months, integrating radiotherapy plans into TPS and generating simulated dose increases based on OE-MRI data. Ethics approval is expected by Oct-25. Anticipated Impact and Dissemination This research aims to implement OE-MRI for pwHGG, track hypoxia during radiotherapy, and simulate dose escalation to improve TCP. Key findings will be shared through publications, presentations at major conferences, and collaboration with five major UK cancer centres. Additional outreach will include newsletters for Patient and Public Involvement and Engagement (PPIE). The ultimate goal is to support a future UK clinical trial to enhance radiation delivery to hypoxic tumour regions, potentially improving patient survival.
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