ESHO, the European Society for Hyperthermic Oncology, held their annual meeting in Warsaw, Poland, from May 22-24, 2019. The conference is centered on clinical hyperthermia, which is commonly achieved with deep regional radiofrequency (RF) heating and either local sensor-based temperature monitoring, or, more recently, noninvasive MRI-based temperature monitoring. In this context, hyperthermia means heating tumor tissue to a temperature range of 41 to 43 degrees C to sensitize the tissue to both radiation and chemotherapy and make these treatments more effective. Alternatively, hyperthermia could be used to trigger local drug release from temperature-sensitive drug carriers, such as liposomes.
Focused ultrasound is well known for its ablation capabilities. When combined with MRI-based temperature monitoring and a real-time feedback mechanism, focused ultrasound is also capable of hyperthermia in the above context. At ESHO 2019, researchers from University Hospital Cologne, Germany, led by Prof. Holger Grüll, presented their technical implementation and first demonstration of MR-guided focused ultrasound—based hyperthermia in a clinical treatment of a patient with a retroperitoneal sarcoma. In this compassionate use case, the team was able to maintain the target temperature in a volume of about 100 ml over a 20-minute time period. This was then combined with a chemotherapy regime.
Compared to classic RF-based heating, focused ultrasound—based hyperthermia could offer a “one-stop shop” for cancer patients when combined with local drug delivery and the ablation capability of focused ultrasound. One possible treatment protocol could first use hyperthermia to sensitize the tumor then inject temperature-sensitive liposome nanocarriers with a chemotherapy drug that is released in the heated tumor and carried to its periphery. In the end, the focused ultrasound intensity would be elevated to ablate the core of the tumor, which would also shut down its vasculature and trap the chemotherapeutic drugs within the tumor. (This concept was published earlier by the Cologne group, Hijnen et al., PNAS 2017.)
The Cologne group also presented results from using focused ultrasound to provide thermal therapy to the porcine pancreas in vivo. In these experiments, the team showed how to overcome the challenges and demonstrate the feasibility of ablating the pancreas, given that the pig is a valid model for the human anatomy and physiology around the pancreas. While focused ultrasound ablation of pancreatic cancer has been demonstrated in humans with ultrasound monitoring, it would offer significant advantages with respect to treatment planning, monitoring, and immediate verification of treatment success.
Hyperthermia as a mechanism of action for focused ultrasound has been investigated in preclinical models for many years. It is finally making its way into clinical cases and demonstrating its utility as another pathway to benefit patients.
The Foundation thanks Thomas Andreae and Prof. Holger Grüll for this meeting report.