Reflections on Pediatric Cancer Therapy, Precision Therapy, and Where Focused Ultrasound May Provide Benefit

Written by Karun Sharma, MD, PhD, and AeRang Kim, MD, PhD

Dr. Sharma and Dr. KimAs we reflect on the last days of Childhood Cancer Awareness Month and think of so many young lives affected and lost, we must strive to do better. We must find drugs that don’t put our young kids at risk of heart issues in their adult lives. We must do away with treatments that affect their developing brains from properly functioning at their highest capacities. We must find new ways to minimize effects on fertility and maximize options should they choose to have children of their own in the future. We must prevent other cancers from occurring later in life due to the treatment of current cancers. This list of “musts” could go on and on … We must find precision treatments that minimize toxicity without sacrificing outcome and continue to improve cure rates for our children with cancer.

Medicine is rapidly changing with advances in science and technology. We wouldn’t have imagined 20 years ago that we would have the power to potentially sequence every tumor that is diagnosed. Precision medicine is becoming a reality through advances in drug development and targeted agents against actionable mutations. Harnessing the power of our immune system through immunotherapy is improving outcome for many patients. However, many of these advances have yet to be fully realized for our youngest and most vulnerable cancer patients. The biology and immunosuppressive microenvironment of many pediatric cancers may be a reason for lack of response, and we must find ways to mitigate this.

Advances in precision medicine are not only limited to the gene. These advances also include image guidance and tumor localization, which have allowed for development of minimally to noninvasive therapies that can destroy tumors with minimal collateral damage, as well as be combined with novel drug delivery mechanisms to more completely and effectively treat residual tumors. These developments have the potential to overcome some of the clinical challenges of acute and late toxicities by offering safer, more precise, targeted treatment.

We became involved in the development of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) because of its potential to change current paradigms in pediatric cancer treatment. MRgHIFU possesses many advantages over conventional therapies for local tumor control because it is completely noninvasive and non-ionizing, is able to treat large volumes through multiple bioeffects, and offers the flexibility to combine with other treatments.

We are currently studying the ability of MRgHIFU to ablate tumors precisely, as well as combination approaches with heat-sensitive chemotherapies to increase local tumor drug concentrations without increasing systemic toxicities. We hope to use its thermal or mechanical bioeffects to increase tumor antigen presentation and provide a tumor microenvironment more favorable to the effects of immunotherapy. We hope to use its ability to affect the blood-brain barrier to improve drug delivery for our hardest to treat pediatric brain tumors. There are multiple MRgHIFU applications that may advance and improve treatment for our pediatric patients with cancer.

Each year, Childhood Cancer Awareness Month is a time for reflection and a call to action for our patients and families whose lives are affected every day by pediatric cancer. Their strength and courage give us hope and optimism that we will do better.

Additional Resources
Children’s National Hospital Becomes Foundation’s First Pediatric Center of Excellence
Research Site Profile: The Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital
Ellie Block Supports Pediatric Research and More

Karun Sharma, MD, PhD is an interventional radiologist at Children’s National Hospital.
AeRang Kim, MD, PhD is a pediatric oncologist at Children’s National Hospital.