In a world's first, Sunnybrook researchers show strong potential to increase the tumour-destroying effects of cancer radiotherapy at lower doses of radiation by using ultrasound in a new way, to disrupt tumour blood vessels through acoustically-stimulated microscopic bubbles, as published in Proceedings of the National Academy of Sciences U.S.A.
Ultrasound is typically used for imaging. Microscopic bubbles or "microbubbles" pass harmlessly through the body's circulation and are normally used as a contrast agent to allow ultrasound to detect cancers or the new growth of blood vessels indicating angiogenesis, critical for tumour growth.
In this study, the researchers for the first time use ultrasound to cause microbubbles to resonate inside tumour blood vessels of preclinical models to destabilize structures, creating greater sensitivity to smaller doses of radiation and amplifying the tumour cell-death inducing effects of radiation treatment.
"Our findings indicate a real possibility for bigger treatment impact at lower radiation doses which would mean less toxicity for patients and potentially less treatments overall," says Dr. Gregory Czarnota, the study's lead investigator, a radiation oncologist at Sunnybrook's Odette Cancer Centre and scientist at Sunnybrook Research Institute.
Findings show a 40 to 50 percent tumour volume cell death after a single 2 Gy radiation dose combined with ultrasound and microbubble treatment given in advance, compared to 5 percent cell death using ultrasound and microbubble treatments or 2 Gy radiation treatment alone. Normally up to thirty-five 2 Gy treatments must be given to achieve comparable amounts of cell death.
Experiments were conducted within prostate cancer tumours, both with single doses of radiation combined with ultrasound and microbubble treatments, and with three-week treatment periods (more typical of a patient's treatment schedule) combined with twice-weekly ultrasound and microbubble treatments. Tumours were assessed for cell death and growth inhibition. In each the combined treatments were more effective.
"This approach could be combined with existing high-precision imaging-guidance for example, MRI-guided devices to carefully target ultrasound effects in cancer patients," says Dr. Czarnota, an assistant professor in the departments of radiation oncology and medical biophysics at the University of Toronto.
The researchers are also conducting preclinical studies of similar approaches for bladder and breast cancers and will publish data later this year.
This study was generously funded by the Terry Fox Foundation New Frontiers Program Project (administered by the Canadian Institutes of Health Research), the Early Researcher Award from the Ministry of Research and Innovation, the Congressionally Directed Medical Research Programme of the U.S. Army, and a Cancer Care Ontario Research Chair Award.