Neuro-Oncology recently published a study on a new method of molecularly diagnosing brain tumours that’s been developed by scientists at the University of Nottingham along with clinicians at Nottingham University Hospitals NHS Trust (NUH).
The new ultra-rapid method will drastically reduce the time it takes to get an accurate molecular classification of a brain tumour. It’s hoped that reducing the time from 6-8 weeks after a biopsy to as little as two hours, will provide people with a more complete diagnosis and prognosis faster. As well as making sure they receive the optimal standard of care in a timely fashion.
The team at NUH utilised the new approach during 50 brain tumour surgeries to deliver a rapid diagnosis while the surgery was happening. This approach achieved a 100% success rate and provided diagnostic results in under two hours from the biopsy being taken.
While these results are extremely promising, it’s important to note that there are still some important steps that need to be taken before this kind of test becomes widely available.
What is a molecular diagnosis of a brain tumour and why is it important?
An MRI or CAT scan can identify that somebody has a brain tumour, as well as showing the size of the tumour and where in the brain it’s located.
This information is usually enough for a healthcare team to understand whether somebody will need surgery to remove or debulk the tumour (this surgery is called a craniotomy). However, there are still many answers they need before they fully understand the brain tumour and can make suggestions about ongoing treatment and care.
By taking a biopsy of the brain tumour – either as part of a craniotomy or as a separate procedure if a craniotomy isn’t needed – they can diagnose the type of brain tumour and what grade it is. With around 130 different types of brain tumour, this information is vital to understanding what treatment might be most effective and what somebody’s prognosis is likely to be.
They can also perform genetic testing that reveals the exact classification of brain tumour somebody has – by which we mean the distinct sub-type of brain tumour that’s based on the molecular makeup of the tumour cells. This is important because even if two people have the same type of brain tumour, they could have different sub-types that behave differently or have different outcomes.
A good example of this is in children diagnosed with a glioma. There’s a sub-type of glioma that has a BRAF V600E mutation and it’s been shown that treating children with this sub-type of glioma using a combination of dabrafenib and trametinib is more effective and causes fewer side-effects.
Currently, these complex genetic tests have to be sent away to be analysed and it can take 6-8 weeks or more to get full results. It’s hoped that by reducing the length of time it takes to receive these results, people will get a more complete diagnosis faster and and help ensure they receive the optimal standard of care in a timely fashion.
How could this test benefit people diagnosed with a brain tumour?
Quicker and more accurate genetic diagnosis
We know that one of the scariest things for people diagnosed with a brain tumour is waiting to find out exactly what kind of tumour they’re diagnosed with and what this means for their prognosis.
It usually takes 6-8 weeks after a biopsy is taken for somebody to receive a complete molecular diagnosis and it currently requires multiple different tests. Cutting this to as little as two hours after the biopsy is taken – and only needing to perform a single test – could greatly reduce the amount and severity of anxiety people feel. It will also hopefully give families affected by a brain tumour more time to process what they’re going through.
Accelerate the most suitable standard of care for patients
Although this test might not be able to help people diagnosed with a brain tumour receive treatment quicker, it could help identify the best standard of care quicker.
An example of this might be somebody who’s diagnosed with a low grade brain tumour, where the most appropriate standard of care would be active monitoring (also known as watch and wait). If it takes 6-8 weeks until the genetic test results come back, that individual and their loved ones are likely to spend that time worrying that the tumour is getting worse and that the delay to receiving treatment could be critical.
Although receiving the results quicker wouldn’t change anything about the decision to not have active treatment, it could mean a lot less anxiety about the fact they aren’t receiving treatment.
Help improve the results of surgery
Surgery to remove or debulk a brain tumour usually takes between four and six hours, but it’s not unusual for the procedure to take longer.
Being able to receive a genetic diagnosis in as little as two hours means the information revealed by the test could even inform the strategy taken by the surgeons during the surgery in real-time.
For example, if the test shows somebody has a more aggressive type of brain tumour, the surgeons might decide to take a more aggressive approach. This would mean removing more of the tumour cells and some of the healthy tissue surrounding the tumour to prioritise preventing recurrence over reducing side-effects.
Alternatively, if the test shows somebody has a less aggressive type of brain tumour, the surgeons might decide to take a less aggressive approach. This would mean minimising the damage to healthy tissue and prioritising reducing the permanent side-effects of the surgery over preventing recurrence – as recurrence would be less likely.
While we don’t yet have concrete evidence that this will prove beneficial to people diagnosed with a brain tumour, the fact that it’s possible is truly astounding. It could mark a significant step forward and become a vital tool in reducing the harm done by brain tumours.
Improve access to research
Often, research projects and clinical trials are limited to people with certain types – or even certain sub-types – of brain tumour. Knowing this information sooner using this new technology could mean the individual has a greater chance of accessing a clinical trial, if they are eligible.
For example, if somebody receives a genetic diagnosis 6-8 weeks after a biopsy is taken, it might be preferable and quicker for somebody to be referred on to the most effective standard of care rather than find appropriate an appropriate research project to take part in and be recruited onto the study.
Alternatively, if somebody receives those results as little as two hours after the biopsy is taken, they might have the time to find an appropriate research project to take part in and be recruited onto the study before they’d be due to begin standard treatment.
What are the next steps?
Although this new test looks promising, there will need to be further validation and comparisons to current diagnostic techniques to facilitate rollout across the NHS. The relative simplicity of this technique will allow a more localised approach to molecular diagnosis and, subsequently, DNA sequence information. This will improve the current significant regional variation in access to accurate molecular diagnosis and DNA sequence information and could facilitate more efficient recruitment into clinical trials.
Colin Watts, Professor of Neurosurgery at the Department of Cancer and Genomic Sciences at the University of Birmingham is overseeing our BRAIN MATRIX project. It aims to help ensure everybody diagnosed with a brain tumour has the opportunity for whole genome sequencing.
He told us: “Long read sequencing (LRS) has the potential to revolutionise the delivery of genomic medicine by accelerating diagnosis and precision treatments. In the Tessa Jowell BRAIN MATRIX platform study, funded by The Brain Tumour Charity, we are excited to be undertaking a pilot study in patients with brain cancer using ONT technology. Already we are seeing amazing results in both diagnosis and analysis of mutations that are much faster than our current NHS standard of care.”
Our Chief Scientific Officer – Dr Simon Newman – said this about the new test developed at the University of Nottingham:
“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 remove 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.”