This month, we highlight the company behind the new focused ultrasound Center of Excellence (COE) in London: Philips Healthcare. Thanks to Philips’ generous support and impressive scientific vision, the COE is established at the Institute for Cancer Research (ICR) at The Royal Marsden Hospital’s Sutton, Surrey site and will advance focused ultrasound treatment of cancer.
To learn more about the MR-HIFU division of this global company, we interviewed Thomas Andreae, PhD, the Marketing Director for MR-Therapy at Philips Healthcare based in Helsinki, Finland. This Q & A session reveals the key technological elements that make the Sonalleve system unique, the company’s vision for new indications, and clinical research that may be on the horizon.
“We want to expand the scope of indications in oncology for our current technology platform beyond pain palliation of bone metastases–we are also looking at primary bone malignancies and soft tissue tumors. Additionally, we have been working closely with Sunnybrook in Toronto and now UTSW in Dallas to advance MR therapy of prostate cancer.” —Thomas Andreae, PhD
Q. In general, what is the current status of the Philips focused ultrasound business?
We have further matured our technology, which is discussed in the next section, and we see a lot of exciting up-and-coming indications. While we see a growing interest in the technology and the potential it offers – demonstrated by the growing popularity of the FUS Symposia, both in the US and in Europe – several factors outside the realm of technology are limiting substantial growth of the MR-HIFU business beyond academic institutions today. Reimbursement for the procedure is problematic in most countries, thus limiting access for patients. We are addressing these issues industry-wide together with the FUS Foundation through the Reimbursement Working Group. We are collaborating on initiatives to facilitate global reimbursement for uterine fibroids through the RELIEF registry, working with the federal government in Germany to get MR-HIFU fibroid therapy into the catalogue of the statutory health insurance of reimbursable procedures, and we have a strategy in place for obtaining payment coding in the US for fibroids and bone metastases.
Q. Tell us about your Sonalleve technology.
The Philips Sonalleve MR-HIFU system has three distinctive technology elements that make the device more effective and substantially improve treatment efficiency, allowing treatment of larger tumors in a shorter time — very important aspects when we want to bring the technology from the academic environment to mainstream community hospitals. These three elements are Volumetric Heating, Direct Skin Cooling, and Treatment Efficiency Optimization using absolute fat temperature measurement based on T2 weighted MRI.
Volumetric Heating – Since the beginning, the Sonalleve MR-HIFU system uses the Philips proprietary volumetric heating technique, enabling a larger volume to be ablated in a shorter time. The size of the ellipsoid-shaped treatment volumes can be adjusted from 4 mm up to 16 mm in diameter and 40 mm in length, leading to a macroscopic ablation zone in a relatively short time. Larger treatment cells cover the target volume better and shorten the treatment time because fewer cooling intervals are required. In addition, the transducer can be lifted, tilted, and some of its elements shut off to avoid sonication of scars, bowel, or bladder if they are in the way of the original beam path.
NEW: DISC – Direct Skin Cooling — The patient’s skin in the area of ultrasound penetration is kept at a constant temperature of about 20°C. The ultrasound window in the table is equipped with a double membrane, and cooled water is circulated between the two membranes. To maximize the cooling efficiency, the patient is positioned directly onto the membrane; a gel pad is typically not needed. The active cooling provided by DISC substantially reduces the wait time between sonications as compared to using a gel pad or no active cooling.
NEW: Treatment Efficiency Optimization — DISC combined with frequent MR temperature measurements in the subcutaneous fat layer (based on T2 weighted MR images) allows the system to suggest appropriate cooling times between sonications. We calibrated the T2 of subcutaneous fat against temperature, which means we directly measure the temperature of the subcutaneous fat and can determine patient adaptive cooling times optimized for treatment efficiency while reducing the risk for adverse events like skin lesions. While total treatment time is dependent on multiple factors, Sonalleve with DISC combined with T2 fat temperature measurements can minimize the time for the procedure. We plan to publish our calibration data and make them available to the community.
Q. What indications is the Sonalleve system approved for around the world?
Treatment for uterine fibroids and adenomyosis is approved in Europe, Canada, Korea, and many other countries. Palliative treatment for painful bone metastases is approved in Europe.
Q. What are your main treatment centers around the world?
Samsung Medical Center in Seoul, Korea has been the most productive and consistent center for fibroid therapy for many years, as demonstrated by a large number of high quality publications and satisfied patients. In Europe, fibroid patients are being treated at multiple centers, including:
- University Medical Center, Utrecht, Netherlands
- Marienhospital in Stuttgart and University Hospital in Lübeck, Germany
- Hospital of the Compassionate Brotherhood, Vienna, Austria
In North America, uterine fibroid patients can be treated at eight centers that are participating in the SOFIA clinical trial, which will support a submission to the FDA for regulatory approval of the Sonalleve MR-HIFU system in the United States.
Q. What clinical research do you have ongoing or planned for the near future?
We want to expand the scope of indications on the current platform further into oncology beyond pain palliation of bone metastases in Europe. While additional clinical research is ongoing for bone metastases (e.g., at the ICR/Royal Marsden COE mentioned in the beginning), we are also looking at primary bone malignancies and soft tissue tumors.
The clinical research for treatment of breast cancer with our dedicated transducer configuration is ongoing at University Medical Center in Utrecht and, soon, at a second site in Switzerland. This is very exciting work, but we will need a lot of data to substantiate any clinical claims before we expect adoption of the technology for this indication. With the two partners, we hope to get a better understanding of patient selection criteria, treatment protocols, and possible pathways into clinical practice.
We have been working closely with Sunnybrook in Toronto and now with University of Texas Southwestern (UTSW) in Dallas to advance MR-guided ultrasound therapy of prostate cancer using a transurethral approach to the prostate. The first experience in a pilot trial is very encouraging, and we are looking forward to seeing this technology come to the benefit of a larger patient population – first in clinical trials and eventually in clinical practice.
We have extended our volumetric heating technology so that we can heat larger volumes homogenously to a temperature in the range of 40 – 45°C. This concept of hyperthermia has been proven to improve the efficacy of both radiation and chemotherapy in selected cancers. With greater precision in temperature through real-time MR temperature measurement and feedback, we see an opportunity to enhance efficacy even more with MR-HIFU. Together with our clinical partners, we are currently preparing a clinical pilot trial and expect to treat the first patient soon.
With this technology, we now have the basis for local drug delivery by means of temperature-sensitive liposomes or similar processes. Several groups are working with experimental formulations of such drug-carrier combinations; however, so far none of these have made it to a level that would allow clinical use. We are working with pharmaceutical companies to help them evaluate their drugs, and some day we will realize the potential we all see in this approach to delivering chemotherapy with high efficacy while reducing side effects.