New Liquid Biopsy Test Detects Brain Cancer, But It Doesn"t Use Blood

Researchers from Memorial Sloan Kettering Cancer Center (MSKCC) in New York have pioneered a new type of liquid biopsy that might be able to monitor the progression and response to treatment of a type of brain tumor. However, unlike most liquid biopsy tests to detect circulating tumor DNA (ctDNA), it does not use blood.

Liquid biopsies using blood have shown that they can detect the presence of several types of tumor, but brain cancers have largely not been picked up with the method. The new study published today in Nature looked at 85 adults with a type of brain cancer called glioma and instead of blood, uses a sample of cerebrospinal fluid (CSF); a colorless liquid made in the brain, which bathes the brain and spinal cord.

Having a brain tumor biopsy for DNA sequencing currently involves highly invasive brain surgery, but to take a CSF sample, doctors perform a comparatively simple procedure called a lumbar puncture (sometimes referred to as a spinal tap) This involves putting a needle between two vertebra in the spine. and although it is undoubtedly unpleasant, adults can generally be awake for the procedure with just local anesthesia.

"Having a minimally invasive test that gives a snapshot of the tumor could open opportunities for clinical trials. Compared to brain surgery to take a biospy, this method is a lot cheaper—this test can be ordered at MSKCC as a standard clinical test now" said Ingo Mellinghoff, Medical Oncologist at MSKCC and lead author of the study.

Sampling the CSF is fairly common in people with many different types of cancer, not just brain cancer where oncologists look for the presence of cells that have shed off the tumors. People with blood cancers also frequently get lumbar punctures to check to see if there are any cancer cells hiding out in their brain and spinal cord, which could then come back at a later date to cause a relapse.

The new research looks for DNA from gliomas, an umbrella term for different types of brain cancer including glioblastoma, a very aggressive form, which Senator John McCain passed away from last year. The DNA is analyzed for the presence of cancer-associated mutations on the MSK-IMPACT panel, developed at Sloan Kettering, the same test which last week was used to predict the response of tumors to immunotherapy.

"The amount of DNA we get out of the CSF is less than we get from a biopsy, but we use the same test MSK-IMPACT. It's tumor DNA in the CSF and it is representative of that tumor," said Mellinghoff.

The team had both CSF and tumor biopsy samples from some patients and they were able to use these matched samples to verify that the DNA test from CSF worked.

"If we collected tumor biopsies and CSF at the same time, they were virtually identical," said Mellinghoff.

Mellinghoff explains that some of the patients in their cohort had their tumor biopsy samples and CSF samples collected at vastly different times, making them difficult to compare as the DNA of the tumor had often changed with time. This in itself is exciting as it raises the possibility that researchers might be able to track how tumors evolve and respond to therapies, enabling them to prescribe treatments that are more likely to help the patient.

However, the test was only able to pick up ctDNA in half of the glioma patients tested and currently the researchers aren't quite sure why. What they do know is that, perhaps unsurprisingly, the larger the tumor, the more likely they are to be able to detect ctDNA. Other possibilities are that some tumors don't release ctDNA into the CSF, or that tumors in certain parts of the brain are more likely to.

"Every hospital in countries like the U.S., U.K., does spinal taps. The uptake of this test in the wider field could be fairly rapid," said Mellinghoff.

The initial study used 85 adult glioma patients from MSKCC, but there are plans to also see if the test might work for other types of brain tumor and also children with brain tumors. There are also some patients who can't have a brain tumor biopsy and without information about the genetic makeup of the tumors, oncologists are somewhat guessing at the best treatments currently.

"We really do have patients whose tumors can't be biopsied because of where they are. This test could broaden access to therapies for these patients," said Mellinghoff.