Charlottesville, Va., October 13, 2021 – In a first-in-world clinical trial, researchers at Sunnybrook Health Sciences Centre in Toronto, Canada, have demonstrated that magnetic resonance (MR)-guided focused ultrasound can be used to safely deliver antibody therapy to breast cancer that has metastasized to the brain.
In this Phase I clinical trial for Her2-positive breast cancer patients, the Sunnybrook team captured images of the antibody therapy, trastuzumab (or Herceptin), precisely targeting tumors in the brain after using Insightec's Exablate Neuro focused ultrasound device to temporarily and noninvasively open the blood-brain barrier (BBB) and enable intravenous trastuzumab to more effectively access tumor sites.
Antibody therapies can help the immune system fight cancer cells, and they are often used in combination with radiation and chemotherapy. However, the BBB presents a challenge when attempting to target sites in the brain. The BBB is a layer of cells lining blood vessels that protects the brain from viruses, bacteria, and other toxins – but it can also prevent therapeutics, such as trastuzumab, from reaching the brain in high enough concentrations to be effective.
"This is the first visual confirmation that focused ultrasound can improve the delivery of targeted antibody therapy across the blood-brain barrier," says Dr. Nir Lipsman, the study’s principal investigator and director of the Harquail Centre for Neuromodulation at Sunnybrook. "These are preliminary, but very promising, results that with continued research have implications well beyond brain cancer for other neurological conditions, including Parkinson's disease and Alzheimer's, where the blood-brain barrier poses a challenge to drug delivery."
The results from the first four patients in this 10-patient trial were published today in Science Translational Medicine in an article entitled, "MR-guided focused ultrasound enhances delivery of Trastuzumab to Her2-positive brain metastases."
Metastatic breast cancer, also known as Stage IV breast cancer, starts in the breast and can spread to the brain, bones, liver, or other organs. Current treatments for breast cancer brain metastases include open neurosurgery, radiation, and chemotherapy. However, depending on the location and number of brain metastases, options for surgery and radiation may be limited, and it can be difficult for therapies to effectively reach tumors in the brain.
"The early data in this study suggest delivery of antibody therapy directly to tumors using focused ultrasound may impact treatment efficacy, with tumors slightly decreasing in size, with varying results for patients between 7 and 31 percent during the study – on average to 21 percent," says Dr. Rossanna Pezo, medical oncologist in the Odette Cancer Centre at Sunnybrook. "The reduction in tumor size is promising but should be interpreted with caution as further research on a larger scale is needed."
These results set the stage for the possibility of delivering a host of both established and novel therapies for numerous brain conditions that otherwise cannot gain access to the brain.
Sunnybrook is a Focused Ultrasound Center of Excellence – the only Canadian site to be recognized as such by the Focused Ultrasound Foundation, which was one of the funders of this clinical trial.
"The multidisciplinary team at Sunnybrook are pioneers in the use of focused ultrasound to treat a variety of brain disorders," says Neal F. Kassell, MD, chairman of the Foundation. "This world-first study demonstrating the effectiveness of focused ultrasound to open the BBB for facilitating delivery of antibodies to the brain is an important milestone in the development of new approaches for treating brain tumors and other neurological disorders. We are pleased to be partnering with this esteemed group."
Read Sunnybrook's Press Release >
Learn More about the Trial from Dr. Nir Lipsman >
Meet the First Patient in the Trial >
See Dr. Lipsman’s Recently Updated Investigator Profile >
Sunnybrook Health Sciences Centre is inventing the future of health care for the 1.3 million patients the hospital cares for each year through the dedication of its more than 10,000 staff and volunteers. An internationally recognized leader in research and education and a full affiliation with the University of Toronto distinguishes Sunnybrook as one of Canada’s premier academic health sciences centres. Sunnybrook specializes in caring for high-risk pregnancies, critically ill newborns, and adults, offering specialized rehabilitation and treating and preventing cancer, cardiovascular disease, neurological and psychiatric disorders, orthopaedic and arthritic conditions and traumatic injuries. The Hospital also has a unique and national leading program for the care of Canada’s war veterans.
About Focused Ultrasound
Focused ultrasound uses ultrasound energy guided by real-time imaging to treat tissue deep in the body without incisions or radiation. It is FDA approved in the United States to treat essential tremor, tremor-dominant Parkinson’s disease, uterine fibroids, pain from bone metastases, osteoid osteoma, and the prostate. Dozens of additional indications are approved outside of the US. The technology is in various stages of research and development for nearly 160 diseases, including Alzheimer’s disease and tumors of the brain, liver, breast, and pancreas.
About The Focused Ultrasound Foundation
The Focused Ultrasound Foundation was created to improve the lives of millions of people worldwide by accelerating the development of this noninvasive technology. The Foundation works to clear the path to global adoption by organizing and funding research, fostering collaboration, and building awareness among patients and professionals. Since its establishment in 2006, the Foundation has become the largest nongovernmental source of funding for focused ultrasound research. For more information, visit http://www.fusfoundation.org.
Photo courtesy of Sunnybrook Health Sciences Centre