Key Points

  • Liquid biopsy is a blood test used to diagnose and monitor treatment of brain tumors.
  • Nine patients with glioblastoma (GBM) underwent liquid biopsy before and after focused ultrasound treatment that disrupted the blood-brain barrier to enhance chemotherapy delivery.
  • This first-in-human study – recently published in Neuro-Oncology – found focused ultrasound enriched the amount of circulating brain tumor biomarkers in the peripheral blood.
  • The results suggest that focused ultrasound could reduce the need for invasive brain tumor biopsies and allow better monitoring of GBM treatment responses.

brain scan fus Sunnybrook liquid biopsy studyA research team from Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, and the University of Toronto has completed the first clinical study to test the ability of focused ultrasound to enhance brain tumor biomarker detection from a routine peripheral blood sample. This technique, called liquid biopsy, could reduce the need for invasive brain biopsies and allow better monitoring of glioblastoma (GBM) treatment responses.

Nine patients with GBM who were enrolled in a clinical trial to open the blood-brain barrier (BBB) with focused ultrasound after chemotherapy administration also underwent liquid biopsy both before and after the focused ultrasound session. Focused ultrasound appeared to increase the amount of brain tumor biomarkers in the blood.

“This is the first clinical study to demonstrate the potential of MRI-guided focused ultrasound to support liquid biopsy for the brain,” says Nir Lipsman, MD, PhD, the study’s principal investigator, neurosurgeon, and director of the Harquail Centre for Neuromodulation at Sunnybrook. “While we are still in the early stages of investigation, our study findings combining focused ultrasound technology with blood sample analysis open up the possibility for less invasive diagnostic strategies in the future which could potentially expand beyond cancer to include neurodegenerative diseases.”

For the liquid biopsy part of the study, the researchers collected blood samples within hours before and after focused ultrasound BBB opening and chemotherapy delivery in patients with GBMs. They then compared these samples with control samples taken from patients in another clinical trial who were undergoing BBB opening in patients without brain tumors.

One of the GBM biomarkers that the scientists were looking for in the bloodstream, cell-free DNA (cfDNA), is released from the brain tumor itself. The level of cfDNA in the blood can indicate the presence and size of a tumor. In the past, the BBB has made it difficult to measure cfDNA from brain tumors. In this study, the focused ultrasound application enhanced the presence of cfDNA and other tumor markers, including identifiable mutations, extracellular vesicles, and proteins.

“Currently, the only other ways to diagnose brain cancer are through invasive brain surgery,” says James Perry, MD, a co-investigator, neuro-oncologist, and scientist in the Odette Cancer Research Program and Hurvitz Brain Sciences Program at Sunnybrook. “To detect cancer biomarkers through a blood test could provide a diagnosis for patients and either avoid an operation or allow the surgery to be planned in advance. This might be helpful for some patients who may be too sick for surgery or have tumors located in areas of the brain that are difficult to access. The hope is for a way to detect and monitor brain tumors frequently, which cannot be done with invasive approaches.”

The study found that the focused ultrasound procedure resulted in an average 2.6 times the amount of cfDNA in the blood compared to before the procedure. In one patient, there was a seven-fold increase in the amount of cfDNA. This study demonstrating enhanced bidirectional flow of material after focused ultrasound BBB opening was published in the journal Neuro-Oncology.

“The Focused Ultrasound Foundation is excited to note this groundbreaking research that could provide a noninvasive approach to ‘biopsy’ a brain tumor,” said Suzanne LeBlang, MD, the Foundation’s Director of Clinical Relationships. “It has the potential to allow for a more comprehensive evaluation of the tumor heterogeneity versus a smaller invasive biopsy of a particular region and can help monitor for disease recurrence earlier than what could be visible on an MRI scan. These advances could change the treatment algorithm and outcome for patients with both benign and malignant brain tumors.”

Ying Meng, MD, the first author of this paper, delivered a Society for NeuroOncology (SNO) presentation on focused ultrasound–enhanced liquid biopsy for brain tumors on Friday, March 19. The event was hosted by Susan Short, PhD, and Houtan Noushmehr, PhD, and attended by more than 45 experts from eight countries. SNO has also incorporated numerous sessions on liquid biopsy for brain tumors at their annual meetings.

See Neuro-Oncology >

See the Sunnybrook Press Release >

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