How Is Proton Therapy Research Benefiting Pediatric Cancer and Multimodal Treatments? Q&A with Dr. Perentesis | Varian

How Is Proton Therapy Research Benefiting Pediatric Cancer and Multimodal Treatments? Q&A with Dr. Perentesis

How Is Proton Therapy Research Benefiting Pediatric Cancer and Multimodal Treatments? Q&A with Dr. Perentesis


Q: What attracted you to the field of pediatric research?

A: I think that taking care of kids and their families is a wonderful privilege. They are always optimistic, resilient, and full of energy. They are my heroes.  When I was training in pediatric oncology, I was impressed that the field directly used the latest advances in science to understanding childhood cancers – and to improve outcomes and cure rates. The average age of a child with cancer is six, so when they are cured they have seven or eight decades of living full and productive lives – it’s awesome to be part of that. I was also attracted to pediatric research because it’s such an open, dynamic and collaborative field. It’s really easy to walk into someone’s lab and talk with them about their research and establish a joint project, and this collegiality extends across the field, both nationally and internationally. Through our fellowship program, we train lots of folks from across the United States, and we have training collaborations with China, Europe and the African subcontinents – so it’s a close knit global community.


Q: What triggered your interest in proton therapy?
A: While our current treatment approaches cure over 80% of kids with cancer, the path to cure is not easy, and there are often severe short- and long-term side effects. Proton therapy is exciting because it offers potential for high efficacy, and early analyses indicate a significant decrease in the risk for long-term side effects. This is particularly important when providing cancer care to children and young adults because they have seven or eight more decades of life ahead of them – so avoiding severe late complications is critical. The other compelling trigger for me was the opportunity to be part of the global efforts to take proton therapy research to the next level. I am drawn to the physics and engineering involved in solving the challenges in proton research such as overcoming uncertainties in dose range, as well as testing new rapid imaging technologies to assure that we are hitting the target.


I am particularly excited in biological research to understand if protons have a mechanism of action that is broader than previously thought. Some very early studies suggest that proton therapy may engage mechanisms to kill some cancers through pathways that are distinct from x-ray therapy. We need to see if this is true, and now have the laboratory tools to investigate these possibilities. We will be also able to explore if tumor genetic alterations render a cancer more or less sensitive to this therapy. There are great opportunities to use biology to refine the use of proton therapy, and how it may be combined with new targeted drugs to improve outcomes. We and other groups are researching the effects of combining protons with the new array of immune therapies that make cancer cells potentially more visible to the immune system to test if this treatment strategy can accelerate the ability of the immune system to attack cancers. This is an exciting time in oncology, and these areas of research hold promise to dramatically change how we think about treating and curing cancer.


Q: Are there any personal experiences that might have influenced your interest?

A: My very first patient as a new attending oncologist was a very young girl with an osteosarcoma. Armed with the good outcome statistics for neoadjuvant chemotherapy and surgery, we optimistically and semi-confidently marched forward with therapy. But it did not follow the textbook. Shortly into intensive therapy, metastases became apparent, and retrieval therapy after retrieval therapy did not work. Her parents were amazing and strong people, and her mother made me promise to work to find cures for kids who are not helped with our current approaches.  So my career basically has followed a path to try to think differently and find new approaches – first in the laboratory, and then at the bedside, to cure these difficult cancers. Two decades later, I think about that patient – as well as my other families – often. It's another reason I am very excited about proton therapy and the potential of integrating it with exciting new approaches in immune targeted treatments and precision genomic-guided drug therapies.  I think that it has potential to be a game changer in oncology treatment.


Q: What makes your approach to proton therapy research unique?

A: I’ve been very fortunate to work at an institution that has been exceptionally supportive of translational research – and willing to take risks and think outside the box. Our Proton Therapy Center is a four room facility, and we made a strong commitment to integrate research by investing $24 million in a research facility in the new building. This includes one entire proton treatment room with a fully functional 360 degree gantry dedicated solely to research, and a suite of laboratories. This focus on research is designed to align with our center’s focus on genomic guided cancer precision therapy, and our goal of exploring if new drugs and immune therapies can increase the efficacy – while decreasing the side effects – of proton therapy. Other unique aspects of our research include our focus on how certain tumors are genetically wired to be responsive to different types of therapies, and why certain patients might be more sensitive to the side effects of chemotherapy or proton therapy and, therefore, more at risk for complications. Our goal is to conduct exciting research and to help catalyze national and international collaborative efforts to propel proton research to the next level to improve patient care.


Q: What makes proton therapy research exciting today?

A: For me, proton therapy is the next frontier in cancer care and research. It is one of four new high impact pillars in research that includes genetically targeted treatments, genome editing, and immune therapies. I believe that all four of these pillars will work together and dramatically change how cancer is treated, and how we move the majority of patients to cure in the next 5 to 10 years. We’ve never had such a confluence of amazing technologies available at the same time. The other exciting part of this research is that it has involved pulling together people from different disciplines with very different world views. For example, we’ve brought together physician researchers, radiation oncologists, physicists, and engineers who all have different perspectives and ideas. This presents an amazing opportunity for us to think outside the box so that we can create better outcomes for our patients.