Brain Imaging May Predict When Liquid Biopsy Would Produce Clinically Actionable Information

Research published in Neuro-Oncology Advances suggested that brain imaging might be able to predict when a liquid biopsy would, or would not, produce clinically actionable information, allowing doctors to better guide patients with newly diagnosed glioblastoma to the appropriate next steps in their care.¹

The key is the ability to image the blood brain barrier and macrophages, which correlate with the amount of circulating DNA in the bloodstream according to the researchers. 

“The more information we have about a tumor, the better,” study senior author Stephen Bagley, MD, MSCE, an assistant professor of Hematology-Oncology at Penn Medicine, said in a press release.⁴ “The combination of being able to measure the integrity of the blood brain barrier, understanding the density of macrophages, and tracking the tumor 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.”

Essentially, the researchers were able to show that an MRI can actually produce a picture of how leaky the blood brain barrier is, and that the higher the volume of tumor with a leaky blood barrier, the higher the levels of plasma cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) are likely to be in a patient’s blood. Furthermore, a correlation was also found between the amount cfDNA and the density of macrophages. 

Using a cohort of 42 adult patients with newly diagnosed glioblastoma, researchers evaluated cfDNA concentration, MRI scans, and tumor histopathology and used linear regression analyses to assess the relationship of plasma cfDNA concentration before surgery to imaging and histopathologic characteristics. In a subset of patients, imaging and histopathologic metrics were also compared between patients with and without a detected tumor somatic mutation. 

“By better understanding the macrophage makeup in a given patient’s tumor, researchers may be able to identify which patients are the best candidates for treatments targeted against macrophages, or for immunotherapy in general,” study lead author Seyed Ali Nabavizadeh, MD, an assistant professor of Radiology at Penn Medicine, said in the release.

Tumor volume with elevated (>1.5 times contralateral white matter) rate transfer constant (K_ep, a surrogate of blood–brain barrier permeability) was found to be independently associated with plasma cfDNA concentration (P = 0.001). Histopathologic characteristics that were independently associated with plasma cfDNA concentration included CD68+ macrophage density (P = 0.01) and size of tumor vessels (P = 0.01). 

Moreover, participants with higher (grade ≥3) perivascular CD68-positive macrophage density had lower volume transfer constant (K_trans, P = 0.01) compared to those with lower perivascular CD68+ macrophage density. Detection of at least 1 somatic mutation in plasma cfDNA was associated with significantly lower perivascular CD68-positive macrophages (P = 0.01). 

Along with demonstrating how imaging may predict the feasibility of liquid biopsy in glioblastoma, researchers also indicated it points to promise of what the combination can find. 

“This study is the first step toward a better understanding of the factors that influence plasma cfDNA concentration and somatic mutation detection in (glioblastoma),” the authors wrote. “Future studies are warranted to investigate the clinical utility of these findings to predict which subset of patients may benefit from liquid biopsy.”

References:

1. Nabavizadeh SA, Ware JB, Guiry S, et al. Imaging and histopathologic correlates of plasma cell-free DNA concentration and circulating tumor DNA in adult patients with newly diagnosed glioblastoma. Neuro-Oncology Advances. doi:10.1093/noajnl/vdaa016.

2. Imaging Can Guide Whether Liquid Biopsy Will Benefit Individual Glioblastoma Patients [news release]. Philadelphia, Pennsylvania. Published February 27, 2020. Accessed February 27, 2020.