By Lina carolina 
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 six to eight weeks, to as little as two hours, a development poised to significantly improve care for thousands of patients annually across the United Kingdom. This groundbreaking advancement, detailed in a new study published in Neuro-Oncology, represents a paradigm shift in the diagnostic process, moving from a lengthy, multi-week wait to near real-time insights, potentially influencing surgical decisions during operations.
A Leap Forward in Diagnostic Speed and Accuracy
Developed collaboratively by researchers at the University of Nottingham and clinicians at Nottingham University Hospitals NHS Trust (NUH), the innovative technique has demonstrated a remarkable 100% success rate in initial trials. During 50 brain tumour surgeries, the team successfully utilized the new approach to provide rapid, intraoperative diagnoses. This means that detailed tumour classifications were achieved within minutes of genetic sequencing, with a fully integrated diagnosis completed within 24 hours of the initial sample acquisition.
The urgency of this development cannot be overstated. In the UK, approximately 34 individuals are diagnosed with some form of brain tumour every day, equating to over 12,000 new cases each year. For the most aggressive forms of brain cancer, the average survival rate can be less than a year, underscoring the critical importance of timely and accurate diagnosis to initiate effective treatment swiftly.
The Traditional Bottleneck: A Slow and Traumatic Process
Historically, the diagnosis of brain tumours has been a complex and protracted affair. The intricate genetic tests required to classify these growths necessitate their dispatch to centralized analysis facilities. This multi-stage process traditionally results in a waiting period of six to eight weeks, or even longer, before patients can be informed of their specific tumour type and prognosis.
This prolonged period of uncertainty is not merely an inconvenience; it is deeply traumatic for patients and their families. Beyond the immense psychological toll, these lengthy delays also postpone the commencement of crucial treatments such as radiotherapy and chemotherapy, potentially diminishing their efficacy and reducing the chances of a positive outcome.
The Nottingham Innovation: From Weeks to Hours
The team of experts in Nottingham has engineered an ultra-rapid method that effectively eliminates this critical delay. Their new technology is so swift that diagnostic results can be obtained within a couple of hours. Crucially, this information can be made available to surgeons during an operation, allowing for informed decision-making that can directly impact the surgical strategy and potentially improve the completeness of tumour removal.
Dr. Stuart Smith, a Neurosurgeon affiliated with the University of Nottingham’s School of Medicine and NUH, highlighted the transformative nature of this advancement. "Traditionally, the process of diagnosing brain tumours has been slow and expensive," he 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 intraoperative potential: "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." This immediate feedback loop represents a significant departure from the current standard of care.
The Science Behind the Speed: Nanopore Sequencing and ROBIN
The current diagnostic pathway typically begins with an MRI scan to detect the presence of a tumour. Following this, patients consult with clinicians to discuss potential tumour types. For many, surgery is then required to obtain a sample. This sample is traditionally sent to centralized labs for genetic testing, specifically to identify abnormalities in the DNA that determine the tumour’s classification.
While neuropathologists historically relied on visual identification of cells, the field has evolved, with tumours now increasingly categorized based on their DNA and genetic abnormalities. However, these genetic analyses have been hampered by technological limitations, leading to the protracted timelines.
Professor Matt Loose, a biologist from the University of Nottingham’s School of Life Sciences, spearheaded the development of the core technology. He devised a method to sequence specific segments of human DNA at high depth using portable sequencing devices from Oxford Nanopore Technologies. This approach allows for the rapid examination of relevant parts of the human genome, with the capability to sequence multiple DNA regions simultaneously, thereby accelerating the entire diagnostic process.
The team has successfully applied this method to genetically test brain tumour samples. Central to their workflow is ROBIN, a software tool that leverages P2 PromethION nanopore sequencers. This system works by detecting minute changes in electrical current as single DNA molecules pass through tiny pores (nanopores) in a membrane, enabling rapid and precise sequencing.
Professor Loose explained the evolution of DNA sequencing: "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." He further noted that their subsequent research, focused on analyzing relevant parts of the genome more quickly, has culminated in the ROBIN platform, capable of producing comprehensive tumour classifications at an unprecedented speed.
"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," Professor Loose added, referring to a key epigenetic marker used in tumour classification.
Once a sample is surgically removed, it is transported to the pathology lab for DNA extraction before being sent to the research team for sequencing.
A Game-Changer for Neuropathology and Patient Outcomes
Dr. Simon Paine, a Consultant Neuropathologist at NUH, expressed strong enthusiasm for the new diagnostic method, deeming it "a game-changer" and "revolutionary." He emphasized that the innovation not only dramatically increases the speed of results but also offers "incredible" accuracy in diagnosis.
The immediate implication of this rapid diagnostic capability is a more informed and potentially more effective surgical approach. For instance, if a tumour is identified intraoperatively as being a particular subtype that is known to be more aggressive or to respond better to certain surgical margins, the surgeon can adjust their strategy in real-time. This precision surgery can lead to better patient outcomes and potentially reduce the need for follow-up surgeries.
Economic Benefits and Wider Implications
Beyond the clinical advantages, the new method also presents significant economic benefits. Professor Loose highlighted that the test is not only quicker and more accurate but also "cheaper than current methods." Their calculations suggest a cost of approximately £450 per person, with the potential for further reductions when scaled up. This cost-effectiveness stems from the ability of the single test to provide comprehensive information that previously required four to five separate analyses, thereby eliminating redundant testing and associated expenses.
The impact on the NHS could be substantial, not only in terms of improved patient care but also in optimizing resource allocation. By reducing the turnaround time and the number of tests required, the healthcare system can potentially treat more patients more effectively with existing resources.
A Call for National Rollout and Future Research
The team at Nottingham is actively pursuing the rollout of this new testing protocol across NHS Trusts throughout the UK. This national dissemination is crucial to ensure equitable access to this advanced diagnostic capability for all brain tumour patients, regardless of their geographical location.
The Brain Tumour Charity has recognized the transformative potential of this technology. Dr. Simon Newman, Chief Scientific Officer at the charity, stated, "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 also pointed to the broader implications for personalized medicine: "The potential to combine so many separate tests into one and deliver at a localized level is a game-changer for driving equity of access to rapid and accurate molecular diagnosis. The BRAIN MATRIX Trial, funded by the Brain Tumour Charity, is now exploring how this technology can match patients to personalized clinical trials across the UK." This suggests that the rapid genetic profiling facilitated by the new method can be integrated into clinical trials, enabling faster identification of eligible patients for novel therapies and accelerating the development of new treatments.
A Glimpse into the Future of Neuro-Oncology
The development at the University of Nottingham and NUH marks a pivotal moment in the fight against brain tumours. By compressing a diagnostic timeline that once spanned weeks into mere hours, this ultra-rapid genetic analysis promises to alleviate patient suffering, optimize treatment strategies, and potentially improve survival rates for thousands. As this technology moves towards wider adoption, it heralds a new era of precision neuro-oncology, where rapid, accurate, and cost-effective diagnosis forms the bedrock of advanced patient care. The journey from initial diagnosis to life-saving treatment has just been dramatically shortened, offering renewed hope to those affected by brain tumours.
