Adults with oligodendroglioma brain tumours now survive more than a decade on average, but the standard photon radiotherapy that controls their tumours can also cause irreversible cognitive decline within two years. This trial tests whether proton beam therapy—which delivers less radiation to healthy brain tissue—can preserve memory, attention, and daily function over five years. The problem is stark: even small cognitive deficits from photon radiotherapy measurably reduce quality of life and ability to work, yet proton therapy is expensive and available at only two NHS centres. Without randomised evidence, funders cannot justify its wider use. This study recruits 246 patients across 18 centres, randomly assigning half to protons and half to photons, then tracks neurocognitive performance annually. If protons prove superior, the impact is concrete: patients retain the ability to manage finances, hold jobs, and care for themselves for years longer. For the NHS, the trial provides the hard data needed to decide whether the higher upfront cost of proton therapy is offset by reduced long-term disability and carer burden. The research also maps which specific brain regions, when spared, most preserve cognition—knowledge that could refine radiotherapy planning for all brain tumour patients.
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Research question: In adults with oligodendroglioma (ODG), does Proton Beam Therapy (PBT) offer neurocognitive benefits compared to photon radiotherapy (RT)? Background: Adults with ODG brain tumours have median survival in excess of 10 years. RT, traditionally delivered using photon radiation, is an important component of treatment. Despite controlling tumour, photon RT can damage healthy brain resulting in long-term irreversible side effects. These include neurocognitive decline (NCD): even small deficits in neurocognitive function (NCF) have an adverse impact on quality of life (QOL) and noticeable impact on daily living, which is especially relevant for ODG patients, given their young age and prolonged survival. NCD may be apparent as soon as two years post-RT and becomes more obvious over time. PBT is an advanced type of RT that delivers less dose to healthy brain, without compromising tumour control. The lower healthy tissue doses from PBT offer the potential for reduced long term toxicity, including reduced NCD. PBT is expensive, new to the UK and available in only two NHS centres. Randomised trials to demonstrate the patient benefits of PBT over photon RT are required in most adult cancers, including ODG. Aims and objectives To determine: i) feasibility of recruitment to a randomised trial of PBT vs. photon RT, ii) whether there are early (2 years post-RT) signals of neurocognitive benefit with PBT compared to photon RT, iii) whether there is a long-term (5 years post-RT) neurocognitive benefit of PBT compared to photon RT. Methods: A multi-centre randomised controlled trial with multi-staged assessment. The primary endpoint is NCF at 5 years, assessed using a standard neurocognitive test battery. Secondary endpoints include QOL, additional tests of NCF, endocrinopathy, safety & toxicity, response rates, progression free and overall survival, carer distress and work & productivity. Patients will be recruited from 18 centres and randomised 1:1 between photon RT and PBT, delivered over 6 weeks at the local centre (photon RT) or PBT centre. Neurocognitive tests will be performed at baseline and annually for 5 years. Clinical assessment, QOL and productivity questionnaires, imaging, blood tests and carer questionnaires will be performed throughout follow-up. Interim analyses will assess recruitment feasibility, early (2-year) efficacy, and exclude futility. The final analysis will be at 5 years. 246 patients (123 per arm) are required to detect a moderate effect size in NCF at 2 and 5 years between PBT and photon RT. Timelines: 12 months for set up, 42 months to recruit, 60 months to complete follow-up and 6 months for analysis/ write up. Mechanism: The aim is to improve understanding of RT dose-NCD relationships in specific brain regions using longitudinal modelling and lesion symptom mapping. This will inform RT planning, prioritising specific regions that can be spared from damage using PBT. This will identify those most likely to benefit from PBT and reduce NCD. Impact and dissemination: A UK study offers a unique opportunity to generate an evidence-base for the benefit of PBT over photon RT. If PBT is superior, individuals in the trial will benefit through access to a treatment that causes less NCD and preserves QOL. From a societal perspective this will enable maintained productivity. This trial will provide high-quality evidence regarding PBT in ODG to guide funding decisions and improve long-term patient outcomes
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