Key Points
- Dr. Dengel is a surgical oncologist who is investigating the intersection of focused ultrasound and immunotherapies.
- Learn more about her current clinical work in melanoma and breast cancer and what’s next.
Lynn Dengel, MD, is a surgical oncologist at the University of Virginia (UVA Health) who is investigating the intersection of focused ultrasound and immunotherapies. She is currently leading a clinical trial assessing the combination of focused ultrasound and immunotherapy for the treatment of melanoma and is also involved with breast cancer studies.
Dr. Dengel serves as a senior advisor for the Foundation, where she helps guide the organization’s strategy for advancing focused ultrasound in the field of cancer immunotherapy.
We recently spoke with Dr. Dengel about her work, her melanoma clinical trial, and what is next.
When and how did you get interested in focused ultrasound?
I began working with my mentor, Craig Slingluff, Jr., MD, during my residency at UVA. He was researching immunotherapy, which was not nearly as well-known of a field then as it is today.
One of the problems we were trying to solve was increasing the ability of the immune system to counteract some of the strategies that tumors use to evade it. We were working on different mechanisms, some involving injections of local immune agents into a tumor, to try to see if we could break up some of the boundaries within the tumor.
Then Dr. Slingluff heard about focused ultrasound through some of our basic science and translational science research partners. We became interested in its potential as a local treatment, not just to kill the tumor, but also to possibly alter the tumor microenvironment to be more susceptible to a patient’s own immune system or immunotherapeutic drugs.
What are your areas of interest in focused ultrasound?
I am interested in the synergistic relationship between focused ultrasound and the immune system. There are good immunotherapeutic drugs available, but they only work for a small percentage of the population. Focused ultrasound is a noninvasive and painless therapy that has shown promise in enhancing immunotherapies or even the immune system itself. If focused ultrasound can improve patient outcomes, it seems like a win for everyone involved.
What mechanisms and clinical indications do you study?
My work is focused on treating breast diseases and melanoma, both of which fall under the umbrella of surgical oncology, a field that incorporates many aspects of medicine. Oncology is a multidisciplinary field, so as surgeons, we work with medical doctors, radiologists, pathologists, and others to solve a problem and develop a plan for each patient.
Tell us about your current clinical trial exploring focused ultrasound for the treatment of melanoma.
Most people think of melanoma as a thin lesion on the surface of the skin, and that is true of most primary tumors. However, when the disease is advanced, it often metastasizes to masses in the lymph nodes or to the soft tissue just beneath the skin. These secondary tumors, which are caused by the spread of melanoma, are the ones that we are targeting in this clinical trial.
The standard of care for patients with surgically resectable advanced stage melanoma is immunotherapy – a checkpoint blockade administered intravenously that essentially helps boost their immune system. Then the tumor is removed and assessed as to whether the immunotherapy worked. But we know that up to 40% of patients do not respond to the immunotherapy.
In our study, we are applying focused ultrasound ablation to the tumor while administering the immunotherapy – before the surgical removal of the tumor. The focused ultrasound partially ablates the tumor and creates an altered area around that ablation zone within the tumor. Early research suggests that this peri-ablation area creates an immunogenic environment that attracts more immune cells. The concept is that we are applying multiple strategies to see if they might be synergistic and in the hopes of improving the number of patients that respond to the immunotherapy. We will assess the tumor after it is removed and compare response rates to see whether there is a significantly improved response in the patients treated with the combination therapy.
How are you using focused ultrasound for breast cancer applications?
My breast cancer research is two-fold. First, I’m developing patient decision-making tools for communicating with patients with the goal of improving the quality of the shared-informed decision-making process.
Additionally, I am collaborating with my colleagues Patrick Dillon, MD, and David Brenin, MD, on a clinical trial using focused ultrasound to treat breast cancer. These patients have primary breast cancer and are planning to have the tumors removed. If a tumor is the appropriate size and in an accessible location for our Theraclion focused ultrasound device, the patient can receive focused ultrasound before resection of the tumor. This trial is also combining the focused ultrasound with an intravenous immunotherapy drug to create a synergistic effect between the immune system and the immunotherapy within the tumor.
What are some of the challenges with incorporating focused ultrasound in immunotherapy?
The main challenge is equipment availability. There are many focused ultrasound devices on the market, and each one is designed to treat different areas of the body. For instance, the device that we are using for our melanoma clinical trial is better at treating lesions that are closer to the skin– it cannot reach targets deep in the body. We must match the device that we have with the problem that we are trying to address and, depending on your location, you may not have access to the correct type of device.
Who are your team members?
I still work closely with Dr. Slingluff, who is a surgical oncologist and has a real focus in translational research around tumor immunology for melanoma. We also work with our medical oncologists on the immunotherapy concepts, meaning they decide on the drug used the regimen.
Rachita Khot, MD, is a radiologist who helps me treat melanomas with focused ultrasound ablation.
Sarah Gradecki, MD, is the dermoatopathologist who assesses the impact of the focused ultrasound on each tissue sample.
We have an outstanding team of clinical research nurse coordinators who review the entire process with patients so they feel well-informed going into a study.
UVA also has several teams of focused ultrasound experts that run laboratories and perform basic science preclinical work. These experts in focused ultrasound and immune outcomes help us on the analysis side.
What are your funding sources?
The Focused Ultrasound Foundation is funding the current melanoma study, and they have invested greatly in the focused ultrasound program at UVA. We also receive support from the University of Virginia Department of Surgery and Cancer Center.
What is most rewarding about your work?
By far, the patients are the best part of my work. Often, doing a research study requires additional patient visits, paperwork, and time. I think of my patients as really doing us a service by participating in these studies, but patients are incredibly grateful as they see it as an opportunity to access treatments that they wouldn’t have at other institutions or off of a trial. What is most rewarding is when patients come back and tell you about their experience and thank you for the work that you’re doing.
How has the Foundation played a role in your work?
Aside from providing funding, the Foundation acts like an incubator of sorts for researchers. It provides a collaborative network with other researchers focused on similar problems at other institutions. It’s also non-competitive; people at other institutions have shared protocols with me, and I’ve shared my protocol with other investigators. That is all thanks to the Foundation. They run workshops and webinars that create a platform for researchers to share both challenges and successes so we can keep research moving forward without silos.
What are your greatest achievements?
This is a challenging question. I think having a surgical oncology practice and being able to do research while also seeing patients in clinic creates an ideal harmony for me. Also, I feel fortunate at UVA to work with outstanding colleagues, staff, residents and medical students.
Any major disappointments?
The pace of research is always slower than I would like. I understand the need for protections and appreciate the focus on patient safety, but I do believe there is opportunity to streamline the approval process for clinical trials.
What is your research wish list?
A true “wish list” would include a research post-doctorate to support the progress and pace of the research and help get the trial data out to the scientific and lay audience faster.
What is next?
I am looking forward to completing this melanoma clinical trial, assessing its results, and expanding on the findings to launch a larger trial.