Use of Cell-free DNA Liquid Biopsy to Predict Glioblastoma Progression

Glioblastoma (GBM) is the most common primary tumor of the central nervous system and is almost always fatal. The aggressive invasion of glioblastoma cells into the surrounding normal brain makes complete surgical removal impossible, significantly increases resistance to the standard therapy regimen, and virtually assures tumor recurrence. Treatment of glioblastoma usually comprises surgical removal of the tumor followed by radiation treatment and chemotherapy using the drug temozolomide (TMZ). These treatments usually fail, mainly due to the presence of a cell subpopulation called glioma stem cells (GSCs), which are resistant to radiation and chemotherapy and capable of self-renewal and tumor generation.

As part of a program to develop methods for predicting the progression of GBM, investigators at the University of Pennsylvania School of Medicine (Philadelphia, USA) sought to determine the prognostic impact of plasma cfDNA as well as its role as a surrogate measure of tumor burden and as the subject for next-generation sequencing (NGS).

For this study, the investigators evaluated 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel.

Results revealed that prior to initial surgery, GBM patients had higher plasma cfDNA concentrations than age-matched healthy controls. Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean was associated with inferior PFS. Thus the 28 patients with lowest pre-surgery concentrations of cfDNA - defined as cfDNA that was below the average of the total group - had almost double the length of progression free survival (median 9.5 months) compared with the 14 patients with highest concentrations (median 4.9 months).

Analysis of cfDNA samples from 20 patients by liquid biopsy detected at least one mutation in 11 patients, and all of those mutations differed from those detected in analysis of each patient's solid tumor biopsy.

"Doctors have begun using liquid biopsies more frequently to monitor certain cancers - particularly lung cancer - in recent years as research has shown their effectiveness in other disease sites. But until now, there has been little focus on the clinical utility of liquid biopsy in brain tumors," said senior author Dr. Erica L. Carpenter, assistant professor of medicine at the University of Pennsylvania School of Medicine.

The study was published in the October 30, 2019, online edition of the journal Clinical Cancer Research.

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