Combining radiation therapy (RT) with focused ultrasound (FUS)-mediated heating and/or mechanical effects is a promising approach for the treatment of radio-resistant tumors where dose escalation is limited due to normal tissue toxicities. This session will cover the development of magnetic resonance-guided high-intensity FUS (MRgHIFU)-based hyperthermia programs in a Radiation Oncology environment. MRgHIFU platforms have recently been adapted for accurate, localized delivery of hyperthermia to a variety of targets. Assessment of the safety and feasibility for targeting different sites involves a number of steps including both prospective studies involving live subjects and retrospective studies using patient data. This process will be discussed using stage IIIA/IVB cervical cancer as an example site, highlighting also how MRgHIFU programs can fit into the Radiation Oncology paradigm as well as ongoing challenges. This session will also cover a recent preclinical study combining FUS-mediated partial tumor ablation with RT. The synergistic biological effects at a cellular level of RT and thermal exposure will be presented and current approaches for biological dose weighting based on cell survival modeling, as well as their advantages and limitations will be discussed. An outlook into systems oncology simulations, accounting for dynamic differences in the cell death mechanisms induced will be given. Also covered in this session is the enhancement of RT by ultrasound stimulated-microbubble mechanical disruption effects. Ultrasound-stimulated microbubble treatment of tumor vasculature can enhance radiation cell death by 40 to 60-fold. The link of this effect to stimulation of the Asmase-pathway, ceramide-linked endothelial cell apoptosis, and vascular collapse will be discussed.
1. Understand the process of assessing the safety and feasibility of performing MRgHIFU-mediated hyperthermia in selected targets.
2. Understand the process and challenges of integrating an MRgHIFU-mediated hyperthermia program into a Radiation Oncology environment.
3. Understanding the biological effects induced by RT and FUS mediated heating alone and in combination.
4. Become acquainted with dosimetric models for combined RT and thermal therapy to enable biological dose weighting based on cell survival.
5. Gain an insight into recent advances in systems oncology simulations for multimodality therapy applications.
6. Understand the physical mechanisms of ultrasound-induced microbubble-facilitated enhancement of radiation response
7. Understand the biological and genetic mechanisms of ultrasound-induced microbubble-facilitated enhancement of radiation response
Funding Support, Disclosures, and Conflict of Interest: Gregory Czarnota is supported by NIH, CIHR and TFRI. Sarah Brueningk is funded under CRUK programme Grant C33589/A19727.