In contrast to high-intensity focused ultrasound (HIFU), which implies high-power and high-temperatures for short durations, focal HT relies on feedback control to maintain a much lower temperature rise (39-45° C) in larger contiguous regions over timeframes that can range from 15 to 60 minutes.  Chris Diederich, PhD and his colleagues at the University of California San Francisco have a new use in mind for their site’s focused ultrasound device (InSightec’s ExAblate 2100 Prostate System). With a $100,000 research award from the Focused Ultrasound Foundation, they plan to modify the MR-guided ablation system so it can be used to deliver focal hyperthermia (HT) – a therapy that heats up tissue and is known to enhance clinical response to radiation therapy and chemotherapy.

   

 

“Recent randomized clinical trials of radiation therapy and HT strongly support improvements in tumor response and control by the addition of HT, especially for advanced and recurrent disease,” Diederich says. “Further, HT can be applied to target delivery of encapsulated or thermally-released drugs – such as Doxil and ThermoDox – and gene delivery, or to enhance immunotherapies.” He believes that focal HT could potentially treat conditions in the prostate and other pelvic sites, such as the cervix and rectum.

Although HT is promising, technical limitations have thwarted its success and acceptance. As Diederich notes, “The heating of deep seated tumors has been hampered by limitations of existing technology, typically electromagnetic or microwave systems, which are very difficult to spatially target and localize heating, and often with sparse thermometry.”

Searching for a solution, UCSF researchers have developed and ed a system that combines High Dose Rate (HDR) brachytherapy with HT using catheter-based ultrasound applicators for treatment of locally advanced cervical and recurrent prostate cancer. (HDR brachytherapy uses thin hollow catheters and a remote afterloader to deliver a precise, three-dimensional dose of radiation to a tumor target volume. Its goal is to deliver a maximum dose of radiation while minimizing exposure of surrounding healthy tissue.) 

Diederich says that studies show the combined therapy “is feasible and works well, with no increased toxicity.”

Study leader Chris Diederich, PhD (center) is shown here with collaborators Joe Hsu, MD, (left) and Vasant Salgaonkar, PhD (right) of the Radiation Oncology Department.

Diederich now wants to move HT to the next level of development by creating a less invasive and more accurate method that combines MRI for target localization and 3-D temperature mapping. His new project will involve modifying the ExAblate 2100 system and evaluating its ability to deliver protracted HT under multi-slice or volumetric MR thermal guidance. Study targets will be ex vivo tissue, phantoms and in vivo models. Diederich and his team will also use advanced patient-specific modeling studies to develop and assess treatment strategies.

The ultimate goal of his research, he says, is to “provide data supporting an FDA investigational device exemption (IDE) application and establish techniques for applying clinical studies of MR-guided hyperthermia within pelvic disease sites.”

The study is a collaborative effort between UCSF researchers in the Radiation Oncology and the Radiology and Biomedical Imaging departments.  

Written by Ellen C., McKenna

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