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Urine and blood tests for brain tumours developed by Cancer Research UK Cambridge Institute



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A world first test that can detect the presence of glioma – a type of brain tumour – in patient urine has been developed by researchers at the Cancer Research UK Cambridge Institute.

They have also created a blood plasma test for glioma during the early-stage research, published in EMBO Molecular Medicine.

Blood plasma
Blood plasma

While it featured only a small number of patients, the results have been described as promising and give hope that the techniques could be used by GPs to monitor patients at high risk of brain tumours.

This would be more convenient than the current standard method, which involves having an MRI scan at a hospital every three months.

This is the approach for those who have a brain tumour removed, who are monitored with scans, followed by biopsies, because of the likelihood of it returning.

“We believe the tests we’ve developed could in the future be able to detect a returning glioma earlier and improve patient outcomes,” said Dr Richard Mair, who is based at Cancer Research UK Cambridge Institute and the University of Cambridge. “Talking to my patients, I know the three-month scan becomes a focal point for worry. If we could offer a regular blood or urine test, not only will you be picking up recurrence earlier, you can also be doing something positive for the patient’s mental health.”

There are already some blood tests for detecting different cancer types in use in the clinic, and they are a significant area of focus for researchers. Most are based on finding mutated DNA shed by tumour cells when they die, known as cell-free DNA (cfDNA).

But detecting brain tumour cfDNA in the blood has proved difficult because of the blood-brain-barrier preventing the passage of cells and other particles, such as cfDNA.

Researchers have explored detecting cfDNA in cerebrospinal fluid (CSF), but the spinal taps needed to obtain it can be dangerous for people with brain tumours.

However, scientists have been aware that cfDNA with similar mutations to the original tumour can be found in blood and other bodily fluids such as urine in very low levels.

The challenge has been developing a test sensitive enough to detect them.

cfDNA is detectable in blood and urine
cfDNA is detectable in blood and urine

The researchers, led by Dr Florent Mouliere at the Rosenfeld Lab of the Cancer Research UK Cambridge Institute and at the Amsterdam UMC, and Dr Mair, developed two approaches in parallel.

The first works for patients who have previously had glioma removed and biopsied. Using a tumour-guided sequencing test, it looks for the mutations found in the tumour tissue within the cfDNA in the patient’s urine, CSF and blood plasma.

Eight patients who had suspected brain tumours based on MRIs were studied, with samples taken at their initial brain tumour biopsies, alongside CSF, blood and urine samples. The test was able to detect cfDNA in seven out of eight CSF samples, 10 out of the 12 plasma blood samples and 10 out of the 16 urine samples.

The second approach explores other patterns in the cfDNA that could indicate the presence of a tumour, without having to identify the mutations.

They analysed 35 samples from glioma patients, 27 people with non-malignant brain disorders, and 26 healthy people using whole genome sequencing, through which all the cfDNA of the tumour is analysed, not just the mutations.

Fragments of cfDNA in blood plasma and urine from patients with brain tumours were different in size to those from patients with no tumours in CSF. A machine learning algorithm was able to differentiate between the urine samples of people with and without glioma.

While cheaper and easier than the first approach, and not requiring a tissue biopsy, this test was not as sensitive and was less specific than the first tumour-guided sequencing approach.

The researchers suggested their tests could be used between MRI scans, and ultimately detect a returning brain tumour earlier.

The team will now compare both tests against MRI scans in a trial with patients with brain tumours who are in remission to see if they can detect if their tumours are coming back at the same time or earlier than the MRI.

If they do, they will explore how to adapt the tests for the clinic, potentially within 10 years.

Michelle Mitchell, chief executive of Cancer Research UK, said: “While this is early research, it’s opened up the possibility that within the next decade we could be able to detect the presence of a brain tumour with a simple urine or blood test.

“Liquid biopsies are a huge area of research interest right now because of the opportunities they create for improved patient care and early diagnosis. It’s great to see Cancer Research UK researchers making strides in this important field.”

Sue Humphreys, from Walsall, a brain tumour patient, said: “If these tests are found to be as accurate as the standard MRI for monitoring brain tumours, it could be life changing.

“If patients can be given a regular and simple test by their GP, it may help not only detect a returning brain tumour in its earliest stages, it can also provide the quick reassurance that nothing is going on which is the main problem we all suffer from, the dreaded ‘Scanxiety’.

“The problem with three-monthly scans is that these procedures can get disrupted by other things going on, such as what we have seen with the Covid pandemic. As a patient, this causes worry as there is a risk that things may be missed, or delayed, and early intervention is the key to any successful treatment.”

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