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 6-8 weeks, to as little as two hours, a breakthrough that could dramatically improve care for thousands of patients each year in the UK. This groundbreaking advancement, detailed in a new study published today in the prestigious journal Neuro-Oncology, promises to transform the diagnostic pathway for one of the most challenging forms of cancer, offering hope for more timely and effective treatment.
The innovative approach, spearheaded by researchers at the University of Nottingham in collaboration with clinicians at Nottingham University Hospitals NHS Trust (NUH), has demonstrated a remarkable 100% success rate in initial trials. During 50 brain tumour surgeries, the new method was utilized to deliver rapid, intraoperative diagnoses. These rapid diagnoses were achieved in under two hours from the time of surgery, with detailed tumour classifications being available within minutes of genetic sequencing. Furthermore, the platform’s continuous sequencing capabilities enable a fully integrated diagnosis within 24 hours, a significant leap from current practices.
The urgency of this development is underscored by the stark reality of brain tumour diagnoses in the UK. On average, 34 people are diagnosed with some form of brain tumour every day, translating to over 12,000 cases annually. For the most aggressive brain cancers, the average survival rate can be less than a year, highlighting the critical need for swift and accurate diagnosis to initiate appropriate treatment promptly.
The Traditional Diagnostic Bottleneck: Weeks of Agonizing Uncertainty
Historically, the diagnosis of brain tumours has been a protracted and emotionally taxing process for patients and their families. The complexity of brain tumours necessitates intricate genetic tests to accurately classify them. Currently, these samples are sent to centralized analysis facilities, a process that can take an agonizing six to eight weeks, or even longer, to yield full results. This extended waiting period not only prolongs patient anxiety and uncertainty about their diagnosis and prognosis but also critically delays the commencement of vital treatments such as radiotherapy and chemotherapy. Such delays can potentially diminish the efficacy of these life-saving interventions, impacting treatment outcomes.
The Nottingham team’s breakthrough directly addresses this critical bottleneck. Their ultra-rapid method eliminates this debilitating delay, offering the potential to deliver diagnostic information within a matter of hours. Crucially, this speed opens the door for this information to be relayed to surgeons during an operation, enabling them to make more informed surgical decisions in real-time.
Dr. Stuart Smith, a Neurosurgeon from the School of Medicine at the University of Nottingham and within NUH, articulated the profound impact of this advancement. "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."
He further elaborated on the surgical implications: "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 real-time diagnostic capability could revolutionize surgical planning, allowing for more precise tumor removal and potentially minimizing the risk of recurrence.
A Journey Through Innovation: From Sequencing to Diagnosis
The current treatment pathway typically begins with an MRI scan to identify the presence of a tumour. Patients then consult with clinicians to discuss potential tumour types. For many, the next step involves surgery to obtain a tissue sample. This sample is then dispatched to centralized laboratories for detailed testing, focusing on identifying abnormalities in the DNA to determine the tumour’s specific type.
While historically neuropathologists would visually examine specimens to identify cells, the field has evolved significantly. In recent years, tumour categorization has increasingly relied on identifying DNA and genetic abnormalities. However, this has traditionally been a slow process due to technological limitations.
Professor Matt Loose, a biologist from the School of Life Sciences at the University of Nottingham, has been instrumental in developing the core of this new technology. He pioneered a method to sequence specific regions of human DNA at high depth using portable sequencing devices from Oxford Nanopore Technologies. This technique allows for the rapid examination of relevant parts of the human genome, with multiple DNA regions being sequenced simultaneously, thereby significantly accelerating the entire diagnostic process. The team has now successfully applied this method to genetically test brain tumour samples.
The Technology Behind the Speed: ROBIN and Nanopore Sequencing
At the heart of this rapid diagnostic system is ROBIN, a sophisticated software tool that works in conjunction with P2 PromethION nanopore sequencers. This technology functions by detecting minute changes in electrical current flow as single molecules of DNA pass through a nanopore – an infinitesimally small hole – in a membrane. This precise mechanism allows for the rapid and detailed analysis of genetic material.
Professor Loose explained the transformative nature of this technological leap: "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," he noted. "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."
The key to the speed lies in the targeted nature of the sequencing. Instead of sequencing the entire genome, which is resource-intensive and time-consuming, the ROBIN platform focuses on specific, diagnostically relevant regions. "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. Methylation patterns are crucial epigenetic markers that play a significant role in tumour development and classification.
Once a tissue sample is obtained during surgery, it is sent to the pathology lab for DNA extraction. This extracted DNA is then promptly sent to the Nottingham team for rapid sequencing.
A Game-Changer for Patient Care and Clinical Practice
The implications of this rapid diagnostic capability are profound, extending beyond just speed. Dr. Simon Paine, a Consultant Neuropathologist at NUH, hailed the new method as "a game-changer, it really is revolutionary." He emphasized, "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." This dual benefit of speed and accuracy is paramount in optimizing patient care.
The team is now actively working towards the widespread rollout of this new testing protocol across NHS Trusts throughout the UK. This initiative aims to ensure that patients across the nation benefit from this transformative diagnostic advancement.
Professor Loose also highlighted the economic advantages of the new approach. "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." This cost-effectiveness is a critical factor in achieving broader accessibility and integration within the healthcare system. By consolidating multiple tests into one comprehensive genetic analysis, the system not only saves money but also significantly reduces the logistical complexities associated with sending samples for various individual analyses.
Broader Impact and Future Directions
The Brain Tumour Charity has lauded the development as a pivotal moment in brain tumour research and patient care. Dr. Simon Newman, Chief Scientific Officer at The Brain Tumour Charity, commented, "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."
The charity recognizes the potential for this technology to address disparities in access to advanced diagnostics. "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," Dr. Newman added. This sentiment underscores the importance of making cutting-edge diagnostic tools available not just in specialized centres but also in local hospitals, thereby leveling the playing field for patients regardless of their geographical location.
Looking ahead, The Brain Tumour Charity is actively involved in exploring the further applications of this technology. The BRAIN MATRIX Trial, funded by the charity, is currently investigating how this advanced diagnostic technology can be utilized to match patients with personalized clinical trials across the UK. This is a critical step towards developing more targeted and effective treatments, moving beyond a one-size-fits-all approach to brain tumour therapy.
This groundbreaking development represents a significant stride forward in the fight against brain tumours. By drastically reducing diagnostic wait times and improving accuracy, the ultra-rapid genetic diagnosis method pioneered by the University of Nottingham and NUH is poised to revolutionize patient care, offering hope and a clearer path towards effective treatment for thousands of individuals annually. The collaborative efforts between academia and the NHS have once again demonstrated the power of scientific innovation to directly address pressing clinical needs and improve patient outcomes on a national scale.
