Key Points
- The preclinical study tested a subcutaneous model of glioma, a more accessible tumor environment than in the brain.
- Focused ultrasound hyperthermia enhanced the effectiveness of radiation therapy, which led to better tumor control.
A University of Virginia (UVA) neurosurgical research team led by Jason Sheehan, MD, collaborated with a UVA pathologist and scientists from the Focused Ultrasound Foundation and LabTAU to conduct a preclinical study evaluating whether focused ultrasound–induced hyperthermia (FUS-HT) could be used to improve the effectiveness of radiation therapy (RT) for treating gliomas. Frédéric Padilla, PhD, the paper’s senior author, leads the Foundation’s Gene and Cell Therapy Program.
The study used an allogenic C6 glioma tumor model that was subcutaneously implanted in rats. To test the hypothesis that the combination of FUS-HT and RT would be more effective than RT alone, researchers treated and assessed tumor growth in four comparison groups, which included RT alone, FUS-HT alone, the FUS-HT plus RT combination, or no treatment.
“In this preliminary study, we chose to work with a subcutaneous tumor model to evaluate the therapeutic potential of FUS-HT in a more accessible tumor environment,” said Dr. Padilla. “Numerical simulations were used to optimize FUS-HT treatment parameters, and a feedback-control loop was implemented to regulate temperature during hyperthermia treatment. A similar approach can be implemented with intracranial tumors in the future and in a clinical setting.”
Mild, 42-degree-Celsius hyperthermia was induced in the tumors by applying focused ultrasound with a single-element, 350 kHz transducer for 20 minutes. RT delivery on the small animal research platform used single-beam irradiation to deliver 2 Gy of radiation. The radiation dose used for this project was determined after a dose-escalation study and was chosen because it allowed enough tumor volume to remain to assess the effects of the combination therapy.
Before treatment (at five days post-implantation), tumor volumes were measured. At one-week post-treatment, the tumors were again measured. As hypothesized, when FUS-HT preceded RT, there was a significant reduction in tumor growth as compared with the other treatments and the control arm.
The researchers therefore concluded that, in this model, FUS-HT enhanced the effectiveness of the RT by inducing more effective tumor control. To evaluate the possible mechanism behind the effect, the team conducted immunohistological analyses of the tumors, and these analyses suggested that the combination treatment led to increased DNA damage.
“When used alone, focused ultrasound–induced mild hyperthermia did not control tumor growth in gliomas,” said Dr. Sheehan. “However, by combining focused ultrasound and radiation, significant tumor growth reduction was achieved. This means that focused ultrasound can potentiate the effect of ionizing radiation on glioblastomas.”
Focused ultrasound–induced mild hyperthermia enhanced the sensitivity of glioma to radiation, which helped control tumor growth in this study. Going forward, these results must now be validated in an intracranial tumor model, and the various therapeutic treatment sequences still need to be optimized.
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