By Nana O 
Scientists and medics have developed an ultra-rapid method of genetically diagnosing brain tumours that will cut the time it takes to classify them from 6-8 weeks, to as little as two hours — which could improve care for thousands of patients each year in the UK. This groundbreaking advancement, detailed in a new study published today in Neuro-Oncology, promises to transform the diagnostic pathway for one of the most aggressive forms of cancer, offering patients faster access to crucial information and potentially life-saving treatments.
A Paradigm Shift in Neuro-Oncology Diagnostics
Developed by a collaborative team at the University of Nottingham and Nottingham University Hospitals NHS Trust (NUH), the novel approach leverages cutting-edge nanopore sequencing technology to achieve an unprecedented speed in identifying the genetic makeup of brain tumours. This innovation addresses a critical bottleneck in current neuro-oncology care, where the lengthy diagnostic process often inflicts significant emotional distress on patients and delays the commencement of timely therapeutic interventions.
The study highlights the successful intraoperative application of this new method during 50 brain tumour surgeries. In these real-world scenarios, the technology achieved a remarkable 100% success rate, delivering diagnostic results in under two hours from the surgical sample collection. Furthermore, detailed tumour classifications were generated within minutes of DNA sequencing. The platform’s continuous sequencing capability allows for a fully integrated diagnosis to be completed within a 24-hour timeframe, a stark contrast to the traditional 6-8 week waiting period.
The Devastating Impact of Delayed Diagnosis
Brain tumours represent a significant public health challenge in the UK, with approximately 34 individuals diagnosed daily, translating to over 12,000 cases annually. The prognosis for many brain tumour types, particularly the more aggressive glioblastomas, can be grim, with average survival rates sometimes falling below a year. This grim reality underscores the critical importance of rapid and accurate diagnosis.
Traditionally, the diagnosis of brain tumours relies on complex genetic testing that necessitates sending tissue samples to specialised, centralised analysis facilities. This protracted process means patients and their families endure an agonizing wait, often for over two months, to learn the precise type of tumour they have and understand their likely prognosis. This prolonged period of uncertainty exacerbates the already immense emotional burden faced by individuals battling a life-threatening illness. Moreover, the delay can significantly impede the timely initiation of radiotherapy and chemotherapy, treatments that are most effective when administered promptly after diagnosis.
The Nottingham Innovation: Speed, Accuracy, and Accessibility
The team of experts in Nottingham has engineered an ultra-rapid genetic diagnostic method designed to eliminate this critical delay. The technology’s speed is so profound that results can be obtained within a couple of hours, with the potential for this information to be made available to surgeons even during the operation itself. This intraoperative insight could profoundly influence surgical decision-making, allowing for more precise tumour removal and potentially improving surgical outcomes.
Dr. Stuart Smith, a Neurosurgeon affiliated with the School of Medicine at the University of Nottingham and NUH, emphasized the transformative nature of this development. "Traditionally, the process of diagnosing brain tumours has been slow and expensive," Dr. Smith stated. "Now, with this new technology, we can do more for patients because we can get answers so much more quickly, which will have a much bigger influence on clinical decision-making, in as little as two hours. Patients find waiting many weeks for results extremely difficult, and this adds to the anxiety and worry at what is already a very difficult time."
Dr. Smith further elaborated on the potential intraoperative benefits: "This type of operation can be quite long, so potentially, a surgeon could be informed during surgery of the accurate diagnosis, which would then impact on the surgical strategy."
A Technological Leap Forward: Nanopore Sequencing at its Core
The current treatment pathway typically begins with an MRI scan to detect the presence of a tumour. Following this, clinicians discuss potential tumour types with patients. For many, surgery is then required to obtain a tumour sample. Historically, this sample would be sent to centralised laboratories for examination. While neuropathologists traditionally relied on visual identification of cells, recent years have seen a paradigm shift towards categorising tumours based on their DNA and genetic abnormalities. However, this molecular analysis has been hampered by technological limitations, leading to the prolonged diagnostic timelines.
Professor Matt Loose, a biologist from the School of Life Sciences at the University of Nottingham, spearheaded the development of a method to sequence specific regions of human DNA with exceptional depth using portable nanopore sequencing devices from Oxford Nanopore Technologies. This innovative technique allows for the rapid examination of crucial genomic regions and the simultaneous sequencing of multiple DNA segments, thereby accelerating the entire diagnostic process.
The team has successfully applied this method to genetically test brain tumour samples. A key component of this system is ROBIN, a software tool that integrates with P2 PromethION nanopore sequencers. ROBIN works by detecting changes in electrical current as individual DNA molecules pass through a nanopore, a microscopic hole in a membrane. This precise detection mechanism allows for rapid and accurate sequencing of targeted DNA regions.
Professor Loose explained the historical context and the significance of their breakthrough: "When we first were able to sequence an entire human genome in 2018, it took around five labs and six months to do, which obviously isn’t ideal when time is of the essence for a patient. This new method now allows us to choose the bits of DNA that we need to look at in order to answer specific questions, such as what type of tumour and how it can be treated. Combined with our later research where we were able to look at relevant parts of the human genome more quickly – then we now have a process where we can use ROBIN to create comprehensive classifications of tumours more quickly."
He further elaborated on the key molecular markers: "Once we have a sample from a patient, we can now quickly extract the DNA and look at the different properties to give us the information we need. Methylation is the one we are most interested in early on in this instance because that defines the tumour type." Methylation patterns are epigenetic modifications that play a crucial role in gene regulation and are known to be altered in various cancers, including brain tumours, serving as important diagnostic and prognostic markers.
A Collaborative Effort for Enhanced Patient Care
The process begins with the surgical removal of a tumour sample. This sample is then transported to the pathology laboratory for DNA extraction before being sent to Professor Loose’s team for sequencing.
Dr. Simon Paine, a Consultant Neuropathologist at NUH, lauded the new method as a "game changer" and "truly revolutionary." He commented, "This new method of diagnosing brain tumours is going to be a game changer, it really is revolutionary. It not only increases the speed at which the results will be available, but the degree of accuracy of the diagnosis as well is incredible."
The team is now actively working towards rolling out this advanced testing across NHS Trusts nationwide, aiming to make this rapid diagnostic capability accessible to a broader patient population.
Economic and Clinical Implications: A Multifaceted Benefit
Beyond its remarkable speed and accuracy, Professor Loose highlighted the cost-effectiveness of the new method. "Not only is the test more accurate and quicker, but it is also cheaper than current methods," he stated. "Our calculations stand at around £450 per person, potentially less when scaled-up. There are a few reasons for this. Our method can eliminate the need for four to five separate tests, reducing costs as a consequence as we are getting more information from the single test we do. Most importantly, it delivers results to the patients when they need them."
The ability to consolidate multiple diagnostic tests into a single, rapid procedure offers significant cost savings for the healthcare system. By reducing the number of separate analyses required, resources can be reallocated, and efficiency can be enhanced. This economic advantage, coupled with the clinical benefits, positions the nanopore sequencing approach as a highly attractive solution for modern healthcare.
A Beacon of Hope for the Brain Tumour Community
The impact of this innovation has resonated strongly within the patient advocacy community. Dr. Simon Newman, Chief Scientific Officer at The Brain Tumour Charity, described the development as "transformative." He remarked, "The delivery of an accurate diagnosis within hours of surgery will be transformative for all patients ensuring rapid access to the optimal standard of care and — crucially — removing the uncertainty patients face when having to wait weeks for their diagnosis and prognosis."
Dr. Newman further emphasized the potential for equitable access: "The potential to combine so many separate tests into one and deliver at a localised level is a game changer for driving equity of access to rapid and accurate molecular diagnosis." This points to a future where geographical location or the availability of highly specialised laboratories will no longer be a barrier to timely and precise diagnosis.
The Brain Tumour Charity is actively involved in exploring the wider applications of this technology. The BRAIN MATRIX Trial, funded by the charity, is currently investigating how this advanced nanopore sequencing technology can be utilized to match patients with personalized clinical trials across the UK, offering hope for novel therapeutic strategies and accelerated drug development.
Future Directions and Broader Impact
The successful implementation of this ultra-rapid diagnostic method at NUH is a crucial first step. The ongoing efforts to disseminate this technology across the NHS signify a commitment to improving outcomes for brain tumour patients nationwide. The implications extend beyond immediate diagnosis; faster genetic profiling can facilitate more informed treatment planning, enabling clinicians to tailor therapies to the specific molecular characteristics of each tumour. This personalized medicine approach holds immense promise for improving treatment efficacy and patient survival rates.
Furthermore, the development showcases the power of interdisciplinary collaboration between academic institutions and clinical settings. The synergy between university researchers and hospital clinicians has been instrumental in translating complex scientific innovation into tangible clinical benefits. As this technology matures and becomes more widely adopted, it is poised to set a new standard of care for brain tumour diagnosis, offering a brighter future for countless patients and their families. The journey from initial research to clinical deployment, though challenging, demonstrates the profound impact that scientific advancement can have on human health and well-being.