Key Points
- Greg Czarnota, MD, PhD, is a clinician-scientist who has spent his career developing innovative ways to treat various types of cancer.
- Learn more about his work using focused ultrasound to improve the efficacy of radiotherapy in patients with breast cancer.
Gregory Czarnota, MD, PhD, FRCPC, is a radiation oncologist and clinician-scientist in the Department of Radiation Oncology at Sunnybrook Health Sciences Centre, a senior scientist in the Physical Sciences Department of Sunnybrook Research Institute, and a professor of radiation oncology and medical biophysics at the University of Toronto. He has spent his career developing innovative ways to treat various types of cancer, including breast cancer.
Although Dr. Czarnota has been using radiotherapy to treat patients with cancer for almost 20 years, over the past 12 years, his research team has been investigating how low-intensity focused ultrasound can potentially increase the effectiveness and safety of radiotherapy in a process called radiosensitization. In fact, Dr. Czarnota’s team is the first in the world to integrate an MRI machine and a focused ultrasound system into a linear accelerator, or “linac” machine – the medical device that is used for radiotherapy treatment.
During Breast Cancer Awareness Month, we are highlighting Dr. Czarnota’s work to test the ability of low-intensity focused ultrasound plus microbubbles to improve the effects of radiation in patients with breast cancer. Earlier this year, he published the data from his first clinical trial treating 20 patients with this technique. Those results demonstrated that the combination of these two therapies improves the success of radiotherapy when it is given after the focused ultrasound. The Foundation is now funding some of his clinical research in this area.
After conducting preclinical and translational studies to determine dosing and optimize energy parameters, Dr. Czarnota conducted the first Phase I clinical trial (NCT04431674) using focused ultrasound plus microbubbles to improve the potency of radiotherapy in participants with advanced breast cancer. Their invasive ductal carcinoma tumors were in the breast or chest wall, and all but one participant had metastatic disease. After briefly stopping to evaluate safety and efficacy results from the first eight participants, the clinical trial enrolled 20 participants. The combination treatment led to a complete response in most of the tumors with minimal side effects.
The final results from the 20-patient study were published in May 2024 in PLoS Medicine. After 3 months, half (n=9) of the 18 tumors showed a complete response and a third (n=6) showed a partial response. The remaining tumors were stable (n=2) or progressed (n=1). At longer follow-up intervals, the local control rates were 94% at 6 months, 88% at 12 months, and 76% at 24-months. The authors concluded that administering two to three treatments of focused ultrasound plus microbubbles throughout radiotherapy:
- Enhanced radiotherapy
- Maintained safety with minimal side effects
- Provided durable local control
- Should be validated in Phase II clinical trials
The Foundation recently began funding a Phase II clinical trial of this work. The new study, NCT06633601, which is a continuation of NCT04431674, is being conducted with a novel focused ultrasound device – the Arrayus Symphony system. The Arrayus device has 6,144 transducers, making it capable of treating larger and more complex tumors – those up to 10 to 15 cm – and treating them more rapidly. It should decrease treatment time from one hour to 10 minutes or less. The first few participants have already been enrolled in this clinical trial, which will include 30 patients with recurrent, inoperable breast cancer in the breast or chest wall. The study is open to anyone who is eligible to have radiotherapy in Canada. Interested patients should contact Dr. Maria Anzola at marialourdes.anzolapena@sri.utoronto.ca.
In a parallel randomized, comparative Phase II clinical trial (NCT06185972), the Sunnybrook team will continue testing the Sonalleve system to determine the efficacy and response of focused ultrasound–stimulated microbubble treatment to enhance radiation effects in participants with advanced breast cancer. In this study, 200 participants will receive focused ultrasound and will be compared in terms of outcomes to a comparably sized group of similar patients being treated with radiotherapy alone, which is the current standard of care. Interested patients should contact Dr. Maria Anzola at marialourdes.anzolapena@sri.utoronto.ca.
In these studies, the Arrayus device permits the rapid treatment of large tumor volumes that are locally advanced whereas the Sonalleve study is predicated on extending results already obtained to a larger patient population. Both studies involve locally advanced or recurrent breast or chest-wall tumors.
Beyond his breast cancer research, Dr. Czarnota is conducting clinical trials for head and neck cancer that also combine focused ultrasound and microbubbles with radiotherapy. He is continuing to design and develop other types of new cancer treatments, uses simulation models to predict their chances of success, and has even invented new ways to evaluate the effectiveness of cancer treatments on the cellular level. For example, Dr. Czarnota and his team discovered a way to use ultrasound imaging and spectroscopy to detect and quantify cell death after chemotherapy and radiation.
To recognize Breast Cancer Awareness month, Dr. Czarnota is a featured guest on the Foundation’s Curing with Sound Podcast. Listen to the episode.
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