By Katie Kosko – Published November 19, 2018 on www.curetoday.com
Researchers have found a potentially safer and faster way to determine if treatment for a type of childhood brain cancer is working, according to early study findings published in Clinical Cancer Research.
The technique is called a liquid biopsy, which tests blood drawn from a patient for circulating tumor DNA — DNA that comes from cancerous cells and tumors. Liquid biopsies are less invasive, more cost-effective and may be able to show changes occurring in the brain from treatment before they appear on scans, such as an MRI, according to researchers.
“If you have a solid tumor that has a certain characteristic — the number of genes and changes in these genes compared with normal tissue — and we realize now that part of the DNA that is specific to the tumor can be detected in the bloodstream,” co-senior author Sabine Mueller, M.D., Ph.D., a pediatric neuro-oncologist at UCSF Benioff Children’s Hospital San Francisco, said in an interview with CURE.
“That’s fascinating when you think about how this can happen for patients with brain tumors because of the blood-brain barrier,” she added. “Normally, we have an intact blood-brain barrier and a lot of medications that we are giving don’t even reach the brain tumor in significant amounts. But we have shown now that we can detect this in the blood.”
The study, which was led by researchers from UCSF Benioff Children’s Hospitals and Children’s National Health System, examined blood and cerebrospinal fluid — fluid found in the brain and spinal cord — samples from 84 children. Diffuse midline glioma (DMG), an aggressive, high-grade brain tumor, was seen in 48 patients and 36 patients had non-central nervous system disease.
Researchers confirmed through the samples that 42 of the children with DMG had H3K27M, a mutation commonly found in patients with this type of brain tumor (about 80 percent), which helps drive the cancer. The level was comparable to what is found using a standard biopsy, which requires surgery, noted researchers.
“We had nice correlation of the amount of circulating tumor DNA in the blood compared to the imaging,” Mueller said. “The question now is what do you believe? And, what is the gold standard? This remains a challenge, but at least for the patient we can clearly see progression.”
DMGs usually occur in children but can also be diagnosed in adults. Brainstem tumors, which comprise the majority of DMG, account for 11 percent of primary brain tumors in children and adolescents, according to the UCSF Brain Tumor Center.
Biopsies for brain tumors are challenging, explained Mueller. And, therefore, understanding how tumors are changing in response to therapy can be difficult. But examining circulating tumor DNA may be a way to get around it. “There is huge potential for this technology, but it has to get more sensitive and specific. It’s a great first step,” she said.
Mueller reiterated that this research is still in its very early stages and not a clinically approved test. “This is an exciting new area for parents and children with brain tumors that we have been able to show that there is circulating tumor DNA on detectable levels in the blood and cerebrospinal fluid for these patients,” Mueller said. “Now we hope to build on the findings to further expand the technology so that in the future we might be able to take a blood sample from the child and then tell the family that this is the type of tumor that they have.”
In addition, study author Javad Nazarian, Ph.D., said that a vulnerable population could be helped by making this technology clinically relevant. “Liquid biopsy provides the opportunity to use blood or cerebrospinal fluid to monitor a tumor that is otherwise inaccessible for molecular studies,” said Nazarian, associate professor at the Children’s National Health System and George Washington University School of Medicine and Health Sciences. “Our data are exciting and will certainly need to be expanded and validated across more cancer cases.”
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