Brain imaging predicts benefit of liquid biopsy in glioblastoma

Tracking brain cancer with a blood test instead of a surgical biopsy may greatly improve quality of life for glioblastoma (GBM) patients and provide critical information for their care, but it is not feasible in all cases. Now US researchers have shown that brain imaging may be able to predict when a blood test known as a liquid biopsy would or would not produce clinically actionable information, allowing doctors to more efficiently guide patients to the proper next steps in their care.

About 12,000 Americans are diagnosed with GBM each year, making it the most common malignant primary brain tumour in adults. It’s also the deadliest, with a five-year survival rate of 5–10%.

The tumours themselves usually contain multiple genetic mutations, which means treatments that focus on one target are normally only partially effective at best. Further, tracking these mutations over time can be difficult, since getting a new tissue sample requires a repeat brain surgery. This is a particularly important issue for GBM since almost all patients experience a recurrence — and when the disease comes back, it often returns with a vastly different genetic make-up.

Liquid biopsy is an alternative way to monitor some cancers, including GBM. With a simple blood test, doctors can measure the amount of cfDNA — circulating DNA that cancer and other cells shed into the blood — as well as circulating tumour DNA (ctDNA), which is the DNA specifically shed by cancer. However, unlike other parts of the body, the brain is protected by the blood–brain barrier, a security gate that controls what gets in and what gets out. Depending on how hard it is for circulating DNA to get in and out of the brain, there may not be evidence of disease in the blood, meaning a liquid biopsy is not helpful in all cases.

Researchers at the University of Pennsylvania revealed that an MRI can provide a picture of how leaky the blood–brain barrier is, and that the higher the volume of tumour with a leaky blood brain–barrier, the higher the levels of cfDNA and ctDNA are likely to be in a patient’s blood. Their study, published in the journal Neuro-Oncology Advances, also found a correlation between the amount of cfDNA and the density of macrophages — a type of white blood cell that makes up a large percentage of the cells inside a GBM and represents a major barrier to the immune system fighting the tumour.

“By better understanding the macrophage make-up in a given patient’s tumour, researchers may be able to identify which patients are the best candidates for treatments targeted against macrophages, or for immunotherapy in general,” said lead author Seyed Ali Nabavizadeh, an assistant professor of radiology at Penn.

In addition to showing how imaging may predict the feasibility of liquid biopsy in GBM, the researchers say it also points to promise of what the combination can find. However, they say further study is needed to understand how this information can affect treatment outcome and disease progression.

“The more information we have about a tumour, the better,” said senior author Stephen Bagley, an assistant professor of haematology-oncology. “The combination of being able to measure the integrity of the blood–brain barrier, understanding the density of macrophages and tracking the tumour through liquid biopsy may be able to help us tailor our treatment decisions so that each patient is getting precision therapy that gives them the best chance of seeing a benefit.”

Image credit: ©stock.adobe.com/au/peterschreiber.media

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