Pediatric Brain Cancer Trial Explores Focused Ultrasound and Liquid Biopsy


Key Points

  • Researchers at Columbia University have begun a trial using focused ultrasound to deliver chemotherapy to progressive diffuse intrinsic pontine gliomas (DIPGs). 
  • DIPGs are devastating, malignant brain tumors that affect young children.
  • In this trial, liquid biopsies will assess focused ultrasound’s impact on circulating tumor markers in the bloodstream.
Medical illustration of a diffuse intrinsic pontine glioma (DIPG).

Researchers at Columbia University have begun a clinical trial to assess the safety and feasibility of using focused ultrasound to facilitate the delivery of chemotherapy to progressive diffuse intrinsic pontine gliomas (DIPGs), a malignant type of brain tumor that affects children. 

DIPGs are highly aggressive and devastating brain tumors that affect young children, typically around the age of five or six. Because the tumors are located in critical areas of the brain, surgical removal is impossible. There are no curative treatments for DIPGs, and only 10 percent of children survive after two years post- diagnosis. 

The blood-brain barrier (BBB) makes DIPGs challenging to treat. This protective layer of tightly joined cells lines the blood vessels in the brain and prevents harmful substances, such as toxins and infectious agents, from entering the brain tissue. However, it can also prevent therapeutic agents – like chemotherapy – from getting into the brain in adequate concentrations to be effective. Focused ultrasound can be used to activate microbubbles inside the brain’s blood vessels. When activated, the microbubbles oscillate and temporarily open the tight junctions between the cells, enabling higher concentrations of therapies to enter brain tissue. 

In this trial, up to 10 participants with DIPGs will receive an oral chemotherapy drug called etoposide before undergoing the focused ultrasound procedure to noninvasively open the BBB at one or two tumor sites. Researchers hope that the focused ultrasound will enable the chemotherapy to penetrate the tumor tissue in higher concentrations. Successful opening and closing of the BBB will be monitored by MRI. The study uses a novel, single-element focused ultrasound transducer under neuronavigational guidance that was designed and tested at Columbia.  

Cheng-Chia “Fred” Wu, MD, PhD, executive lead of the Initiative for Drug Delivery Innovation (IDDI) for Childhood Brain Tumors at Columbia, is leading the study.

Another interesting aspect of this clinical trial is the use of liquid biopsy. A relatively new technique, liquid biopsies analyze the molecular profile of tumors through blood tests or cerebrospinal fluid analysis. Many solid tumors throughout the body shed biomarkers that circulate throughout the bloodstream in significant quantities that can be detected in liquid biopsies. However, in the case of brain tumors, the BBB inhibits tumor markers from entering the bloodstream. Researchers hope that the focused ultrasound-induced BBB opening will allow the tumor markers to exit the brain tissue and reach the bloodstream much in the same way that drugs can be allowed in.  

Researchers will collect blood samples before and after BBB opening to assess any impact that the focused ultrasound may have on circulating tumor markers and how these markers may respond to the cancer-fighting drug delivery.  

“The blood-brain barrier is critical for protecting our brain from toxins and infectious agents; however, in the setting of brain tumors, it also prevents effective drugs from leaving the bloodstream to enter the brain to fight the cancer. Using focused ultrasound to open the protective barrier allows effective drugs to enter the brain but also creates a potential window of opportunity for cancer-related biological information to be released,” said Dr. Wu. “Being able to noninvasively detect and determine the biological changes of the cancer may have huge implications. The American Society of Clinical Oncology Young Investigator grant allows our Neurosurgery Resident, Dr. Nina Yoh, the opportunity to further explore the feasibility of detecting the circulating tumor markers after focused ultrasound in our clinical trial.” 

Dr. Yoh and Dr. Wu work in a multidisciplinary fashion with the Departments of Bioengineering, Neurosurgery, Pediatrics, and Radiation Oncology to advanced focused ultrasound for children with DIPG. 

This trial is being co-funded by the Focused Ultrasound Foundation and supported by Hope and Heroes and the Fegel Family Foundation. 

For Patients 

For those interested in learning more about this trial, please contact research nurse practitioner, Jessica Fino, NP, via email at

Read More on Clinical (NCT05762419)