November 04, 2019
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Plasma cell-free DNA may predict glioblastoma progression

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Stephen J. Bagley, MD, MSCE
Stephen J. Bagley

Plasma cell-free DNA appeared to be an effective biomarker for tumor burden and a viable prognostic tool for disease progression among newly-diagnosed patients with glioblastoma, according to results of a prospective study published in Clinical Cancer Research.

Liquid biopsy also may complement genetic sequencing in solid-tissue biopsies, researchers wrote.

“The liquid biopsy DNA sequencing detected some tumor mutations that were not detected when a piece of the tumor tissue itself was subjected to DNA sequencing,” Stephen J. Bagley, MD, MSCE, assistant professor of medicine at Hospital of University of Pennsylvania, told HemOnc Today. “This may have occurred because, when you do tissue sequencing, you are only able to sequence from one small part of the tumor. Liquid biopsy may be able to sample the tumor genetics more broadly.”

Use of liquid biopsies has increased because of their ability to detect circulating tumor DNA in a minimally invasive way. Even a small amount of circulating tumor DNA from the larger cell-free DNA pool can be used as a substrate for tumor molecular profiling to detect mutations sensitive and resistant to targeted therapies.

The genetic makeup of a glioblastoma tumor can change over time. Currently, the only ways for physicians to learn about these changes are to conduct repeat brain tumor sampling through a craniotomy with tumor resection or stereotactic brain biopsy. Both methods are highly invasive.

“Our hypothesis is that the combination of tissue biopsy and liquid biopsy may provide a more complete picture of the tumor’s genetics compared to doing only tissue biopsy,” Bagley said.

Bagley and colleagues collected blood samples from 42 adults (median age, 65 years; range, 20-81) with newly-diagnosed glioblastoma. The researchers calculated plasma cell-free DNA before initial tumor resection and regularly throughout chemoradiotherapy. They also drew blood from 42 age-matched healthy adults (median age, 62 years; range, 22-82) who served as controls.

Researchers assessed the feasibility of liquid biopsy and its associations with PFS and OS, correlated with radiographic tumor burden and subjected to a targeted next-generation sequencing panel.

Results showed that patients with glioblastoma had higher plasma cell-free DNA concentration than healthy adults (mean, 13.4 ng/mL vs. 6.7 ng/mL; P < .001).

The concentration of plasma cell-free DNA appeared significantly associated with total radiographic tumor burden on first post-radiation MRI scan (P = .003). Concentration tended to increase before or during radiographic tumor progression.

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The 14 patients with preoperative plasma cell-free DNA concentration above 13.4 ng/mL achieved shorter median PFS than the 28 patients with lower concentration (4.9 months vs. 9.5 months; P = .038).

The detection of one or more somatic mutations in plasma cell-free DNA occurred in 55% of patients and appeared associated with decreases in median PFS (6 months vs. 8.7 months) and OS (5.5 months vs. 9.2 months), although the differences did not reach statistical significance. These mutations were different than those detected by tissue biopsy.

Some of the mutations detected may represent subclonal passenger events that have no biologic or clinical relevance, and researchers acknowledged this as the study’s primary limitation.

“We need larger studies to confirm our results, but our initial results raise the question of whether liquid biopsy is, indeed, complementary to tissue biopsy in glioblastoma," Bagley said. “If we can confirm in larger studies that liquid biopsy provides meaningful genetic information about the tumor, this may lead to us being able to track the glioblastoma tumor genetics over time with fewer invasive brain procedures.” – by John DeRosier

For more information:

Stephen Bagley, MD, can be reached at Perelman School of Medicine at University of Pennsylvania, 10th Floor, South Pavilion, 3400 Civic Center Blvd., Philadelphia, PA 19104; email: sbagley@pennmedicine.upenn.edu.

Disclosures: The researchers report no relevant financial disclosures.