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Liquid biopsy spots aggressive paediatric brainstem cancer earlier without surgery

A particularly aggressive form of paediatric cancer can be spotted reliably by the genetic fragments it leaves behind in children's biofluids, opening the door to non-surgical biopsies and providing a way to gauge whether such tumours respond to treatment, according to an abstract presented by Children's National Health System researchers during the Society for Neuro-Oncology (SNO) 2017 Annual Meeting.

Children diagnosed with diffuse midline histone 3 K27M mutant (H3K27M) glioma face a poor prognosis with a median survival time of only nine months after the paediatric brainstem cancer is diagnosed.

Right now, clinicians rely on magnetic resonance imaging (MRI) to gauge how tumours are growing, but MRI can miss very small changes in tumour size.

The Children's research team led by Javad Nazarian, Ph.D., M.S.C., scientific director of Children's Brain Tumor Institute, tested whether circulating tumour DNA in patients' blood and cerebrospinal fluid would provide an earlier warning that tumours were growing.

Just as a detective looks for fingerprints left at a scene, the new genetic analysis technique can detect telltale signs that tumours leave behind in body fluids.

"We continue to push the envelope to find ways to provide hope for children and families who right now face a very dismal future. By identifying these tumours when they are small and, potentially more responsive to treatment, our ultimate aim is to help children live longer," says Eshini Panditharatna, B.A., study lead author.

"In addition, we are hopeful that the comprehensive panel of tests we are constructing could identify which treatments are most effective in shrinking these deadly tumours."

The researchers collected biofluid samples from 22 patients with diffuse intrinsic pontine glioma (DIPG) who were enrolled in a Phase I, Pacific Pediatric Neuro-Oncology Consortium clinical trial.

Upfront and longitudinal plasma samples were collected with each MRI at various stages of disease progression.

The team developed a liquid biopsy assay using a sensitive digital droplet polymerase chain reaction system that precisely counts individual DNA molecules.

"We detected H3K27M, a major driver mutation in DIPG, in about 80 percent of cerebrospinal fluid and plasma samples," Panditharatna says.

"Similar to adults with central nervous system (CNS) cancers, cerebrospinal fluid of children diagnosed with CNS cancers has high concentrations of circulating tumour DNA. However, after the children underwent radiotherapy, there was a dramatic decrease in circulating tumour DNA for 12 of the 15 patients (80 percent) whose temporal plasma was analysed."

Nazarian, the study senior author adds: "Biofluids, like plasma and cerebrospinal fluid, are suitable media to detect and measure concentrations of circulating tumour DNA for this type of paediatric glioma. Liquid biopsy has the potential to complement tissue biopsies and MRI evaluation to provide earlier clues to how tumours are responding to treatment or recurring."

Source: Children's National Medical Center

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