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.
The groundbreaking method, which is detailed in a new study published today in Neuro-Oncology, has been developed by scientists at the University of Nottingham along with clinicians at Nottingham University Hospitals NHS Trust (NUH).
In the published work, the team at NUH utilised the new approach during 50 brain tumour surgeries to deliver rapid, intraoperative diagnoses. This approach has achieved a 100% success rate, providing diagnostic results in under two hours from surgery and detailed tumour classifications within minutes of sequencing. Moreover, the platform's ability to continue sequencing enables a fully integrated diagnosis within 24 hours.
Every day in the UK 34* people are diagnosed with some form of brain tumour, equating to more than 12,000 cases a year. The average survival rate can be less than a year for the most aggressive brain cancers.
Brain tumours require complex genetic tests to diagnose, which clinicians currently have to send away to centralised analysis facilities. It can take 6-8 weeks or more to get full results to be able to inform patients what type of tumour they have and their prognosis. This long wait is extremely traumatic for patients, and also delays the start of radiotherapy and chemotherapy which may reduce the chances of treatment working.
The team of experts in Nottingham have developed an ultra-rapid way of genetically diagnosing brain tumours that will eliminate this delay. The method is so quick that they can even get results within a couple of hours and potentially make this information available to the surgeon during the operation to inform surgical decision making.
Dr Stuart Smith is a Neurosurgeon from the School of Medicine at the University and within NUH.
He said: "Traditionally, the process of diagnosing brain tumours has been slow and expensive. 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."
"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."
The current treatment pathway starts with an MRI scan to ascertain the presence of a tumour, patients will speak to clinicians to discuss the possibilities of what type of tumour they may have. For many tumour types people would then undergo some form of surgery to obtain a sample of the tumour, which currently is sent away to centralised labs for testing to look for abnormalities in the DNA – which will determine what type of tumour it is.
Traditionally experts would then look at the specimens and the neuropathology view would be to try and identify the cells visually. But in the last few years the process has changed and tumours are categorised on the DNA and genetic abnormalities – which traditionally is a slow process due to technological limitations.
Professor Matt Loose, a biologist from the School of Life Sciences at the University of Nottingham developed a method to sequence specific parts of human DNA at higher depth using Oxford Nanopore Technologies portable sequencing devices. This method allows relevant parts of the human genome to be examined much more quickly and multiple regions of DNA sequenced at the same time – speeding up the whole process.
The team have now used this method to genetically test brain tumour samples.
ROBIN, a software tool based on the P2 PromethION nanopore sequencers, sequences the DNA by detecting the change in current flow as single molecules of DNA pass through a nanopore – or tiny hole – in a membrane.
Professor Loose said: "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 can it 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.
"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."
Once a sample has been removed during surgery, it is sent to the pathology lab, where they would extract DNA before it being sent to the team to sequence.
Dr Simon Paine, a Consultant Neuropathologist at NUH said: "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 are now looking to get the new testing rolled out at NHS Trusts across the UK.
"Not only is the test more accurate and quicker, but it is also cheaper than current methods," said Professor Loose. "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."
Dr Simon Newman, Chief Scientific Officer at The Brain Tumour Charity, said: "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 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. The BRAIN MATRIX Trial, funded by the Brain Tumour Charity, is now exploring how this technology can match patients to personalised clinical trials across the UK."
Patient
Charles Trigg is 45 and from Leicestershire. He was diagnosed with a stage 4 aggressive glioblastoma in April. The results of his genetic tests, which help to assess how sensitive the tumour will be to chemotherapy, to give him a more accurate prognosis, and to allow access to clinical trials in the future are crucial.
The current waiting time on these results is around 8 weeks. This new method has reduced this wait to a week.
Charles said: "From my point of view – to have knowledge is power and it could be the worst knowledge you have, but it gives you certainty and having that certainty actually makes life a hell of a lot easier.
"The fact they've been able to get back data very quickly that allows an extensive team of people to conduct detailed reviews feels like an amazing blend of science and medicine.
"The pace is phenomenal, and it gives you that certainty and clarity, regardless of whether you like the information, I can't change the information, but what I can do, is take the information I've been given early - and absorb it, feel it and start to plan for the next stage.
"Do I want to have it? No! Should anyone have it? No! But to have that understanding and that knowledge, it certainly helps and makes the experience a lot, lot easier, than not knowing."
