Key Points
- Focused ultrasound could offer a noninvasive option to patients suffering from these malignant tumors.
- This article from Foundation team members and colleagues at the University of Virginia highlights the state of research for sarcomas and current clinical trials.
Sarcomas are rare cancers that form in bone and soft tissues. They are notoriously difficult to treat, often resistant to chemotherapy, and prone to returning even after surgery. A new review published in Current Oncology spotlights how focused ultrasound could change the outlook for patients and clinicians who are facing these challenging tumors. The Foundation’s associate director of the Research and Education Team, Lauren Hadley, MD, MBA, and research administrator Nicolle Sul contributed to the publication, along with colleagues at the University of Virginia.
The standard of care for most sarcomas is surgery, sometimes paired with chemotherapy or radiation. However, some sarcomas are inoperable due to the location, size, or extent of the tumor. If surgery is an option, it can carry significant risks, and recurrence rates remain high. Sarcomas also tend to have “cold” tumor microenvironments, meaning they do not respond well to immunotherapies that are effective in other cancers.
The review article outlines four ways focused ultrasound can be harnessed against sarcomas:
- Thermal ablation: Using ultrasound energy to generate heat to destroy tumor cells
- Histotripsy: A non-thermal approach that mechanically breaks down cancer cells with high precision and can stimulate immune responses
- Sonodynamic therapy: Combining ultrasound with unique drugs called sonosensitizers that concentrate in tumors and are activated by focused ultrasound to kill cancer cells
- Hyperthermia-based drug delivery: Non-damaging heat to trigger drug release from thermosensitive liposomes, allowing for targeted delivery to the tumor while reducing toxicity to the rest of the body
Focused ultrasound researchers have tested focused ultrasound across multiple settings:
- Preclinical studies in rodents have shown that focused ultrasound can shrink tumors, boost immune responses, and improve delivery of chemotherapy.
- Veterinary studies in dogs and cats with naturally occurring sarcomas have demonstrated that both ablation and histotripsy are safe and can stimulate immune activity.
- Clinical studies in humans suggest that focused ultrasound thermal ablation can achieve local control or symptom relief in osteosarcoma, leiomyosarcoma, myxofibrosarcoma, and spindle cell sarcoma, with some cases showing long-term control on follow-up.
What’s Next
While early results are promising, most human studies so far have been small case reports. There are two larger clinical trials are now underway, however.
One study (NCT04123535) is being led by Matthew Bucknor, MD, at the University of California–San Francisco. It is exploring the safety and feasibility of partial ablation of undifferentiated pleomorphic sarcomas while also measuring various immune effects of focused ultrasound.
Another clinical trial (NCT05111964) is taking place at Oxford University Hospitals NHS Trust and being led by Paul Lyon, FRCR, DPhil. This one aims to determine the safety and feasibility of using focused ultrasound ablation to treat resectable and unresectable sarcomas and unresectable small symptomatic intra-abdominal desmoid tumors. The team is also examining the immunological response of the body to focused ultrasound ablation of these tumors.
“Focused ultrasound could become a powerful new option for patients with various types of sarcomas—as a stand-alone therapy, a way to enhance drug delivery and immunotherapeutics, or an adjunct to surgery,” said Dr. Hadley. “For patients with inoperable or recurrent disease, this noninvasive approach could offer hope where few options exist. My hope is that this review article highlights the need for additional clinical trials to continue to advance focused ultrasound for sarcomas.”
Read “Focused Ultrasound for Sarcomas: A Narrative Review” (Open Access)
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