Posts

banner year

2017: A banner year for innovation at Children’s National

banner year

In 2017, clinicians and research faculty working at Children’s National Health System published more than 850 research articles about a wide array of topics. A multidisciplinary Children’s Research Institute review group selected the top 10 articles for the calendar year considering, among other factors, work published in high-impact academic journals.

“This year’s honorees showcase how our multidisciplinary institutes serve as vehicles to bring together Children’s specialists in cross-cutting research and clinical collaborations,” says Mark L. Batshaw, M.D., Physician-in-Chief and Chief Academic Officer at Children’s National. “We’re honored that the National Institutes of Health and other funders have provided millions in awards that help to ensure that these important research projects continue.”

The published papers explain research that includes using imaging to describe the topography of the developing brains of infants with congenital heart disease, how high levels of iron may contribute to neural tube defects and using an incisionless surgery method to successfully treat osteoid osteoma. The top 10 Children’s papers:

Read the complete list.

Dr. Batshaw’s announcement comes on the eve of Research and Education Week 2018 at Children’s National, a weeklong event that begins April 16, 2018. This year’s theme, “Diversity powers innovation,” underscores the cross-cutting nature of Children’s research that aims to transform pediatric care.

Karun Sharma

Osteoid osteoma successfully treated with MR-HIFU

Karun Sharma

Doctors from the Sheik Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System have completed a clinical trial that demonstrates how osteoid osteoma, a benign but painful bone tumor that commonly occurs in children and young adults, can be safely and successfully treated using an incisionless surgery method called magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU).

Published in The Journal of Pediatrics on Aug. 17, 2017, the study compares nine patients, ages 6 to 16 years old, who were treated for osteoid osteoma using MR-HIFU with a nine-patient historical control group, ages 6 to 10 years old, who were treated at Children’s National using radiofrequency ablation (RFA) surgery, the standard treatment at most U.S. hospitals. The study results show that treatment using MR-HIFU is feasible and safe for patients, eliminating the incisions or exposure to ionizing radiation that is associated with the RFA procedure. Children’s National is the first U.S. children’s hospital to successfully use MR-HIFU to treat osteoid osteoma.

CT-guided RFA, the most commonly used osteoid osteoma treatment, requires drilling through muscle and soft tissue into bone and also exposes the patient and operator to radiation from the imaging necessary to guide the probe that is inserted to heat and destroy tumor tissue.

“Our objective is to provide a noninvasive treatment option for children with osteoid osteoma and we’re very pleased with the results of this clinical trial,” says Karun Sharma, M.D., Ph.D., director of Interventional Radiology at Children’s National and principal investigator for the osteoid osteoma trial. “We have now shown that MR-HIFU can be performed safely with clinical improvement that is comparable to RFA, but without any incisions or ionizing radiation exposure to children.”

High-intensity focused ultrasound therapy uses focused sound wave energy to heat and destroy the targeted tumor under MRI guidance. This precise and controlled method does not require a scalpel or needle, greatly reducing the risk of complications like infections and bone fractures. It is also a faster treatment option, with expected total procedure time of 90 minutes or less. In the U.S., MR-HIFU is used to treat uterine fibroids and painful bone metastases from several types of cancer in adults, but has not previously been used in children.

This breakthrough is the latest from the Image-Guided Non-Invasive Therapeutic Energy (IGNITE) program, a collaboration of the Sheikh Zayed Institute and the departments of RadiologyOncologySurgery, and Anesthesiology at Children’s National. The goal of the IGNITE program is to improve the quality of life and outcomes for pediatric patients through the development and clinical introduction of novel minimally invasive and noninvasive surgery technologies and combination therapy approaches. The team is led by Peter Kim, M.D., Ph.D., vice president of the Sheikh Zayed Institute.

“The use of MR-HIFU ablation of osteoid osteoma is a perfect example of our mission in the Sheikh Zayed Institute to make pediatric surgery more precise, less invasive and pain-free,” says Dr. Kim. “Our leading team of experts are also exploring the use of MR-HIFU as a noninvasive technique of ablating growth plates and pediatric solid tumors. We also have another clinical trial open for children and young adults with refractory soft tissue tumors, which is being performed in collaboration with Dr. Bradford Wood’s team at the National Institutes of Health, and if successful, it would be the first in the world.”

In addition to Drs. Sharma and Kim, the Children’s National team for the ablation of osteoid osteoma clinical trial included: AeRang Kim, M.D., Ph.D., pediatric oncologist; Matthew Oetgen, M.D., division chief of Orthopaedic Surgery and Sports Medicine; Anilawan Smitthimedhin, M.D., radiology research fellow; Pavel Yarmolenko, Ph.D., Haydar Celik, Ph.D., and Avinash Eranki, engineers; and Janish Patel, M.D., and Domiciano Santos, M.D., pediatric anesthesiologists. Ari Partanen, Ph.D., a senior clinical scientist from Philips, was also a member.

Karun Sharma, M.D., poses with two patients

Treating osteoid osteoma with MR-HIFU

Karun Sharma, M.D., poses with two patients

Karun Sharma, M.D., poses with two patients who participated in the MR-HIFU trial for pediatric osteoid osteoma.

Doctors from the Sheikh Zayed Institute for Pediatric Surgical Innovation and surgeons from Children’s National are the first in the U.S. to use Magnetic Resonance-Guided High-intensity Focused Ultrasound (MR-HIFU) to treat pediatric osteoid osteoma.

The trial, led by Principal Investigator Karun Sharma, M.D., Ph.D., Director of Interventional Radiology at Children’s National, began in 2015 and is demonstrating early success in establishing the safety and feasibility of noninvasive MR-HIFU as an alternative to the current, more invasive approaches to remove tumor tissue.

Osteoid osteoma is a painful, but benign, bone tumor that commonly occurs in children and young adults. Removal generally requires orthopaedic surgery to scrape the tumor from the bone or CT (computerized tomography) image-guided radiofrequency ablation (RFA), which is less invasive than surgery but is associated with ionizing radiation exposure and requires drilling through muscle and soft tissue into bone.

MR-HIFU, on the other hand, is a precise and controlled method that does not require a scalpel or needle, greatly reducing the risk of complications, including infections and bone fractures. Even better, it promises reduced procedure time, typically an hour or less.

“Our team set out to provide a noninvasive and radiation free treatment option for children with osteoid osteoma and our pilot feasibility and safety trial is almost completed. We have treated 9 patients and we’re very pleased with the success of the treatments so far. Although follow up will continue for another year, results to date that show that MR-HIFU may be a completely non-invasive and radiation free treatment for osteoid osteoma,” Dr. Sharma says. “Several of the children we treated were very active prior to the onset of their tumor, one a soccer player and the other a swimmer, but because of pain from the tumor, they were unable to enjoy their favorite activities, until now.”

“The use of MR-HIFU ablation of osteoid osteoma is a perfect example of our mission in the Sheikh Zayed Institute to make pediatric surgery more precise and less invasive,” adds Peter Kim, M.D., C.M., Ph.D., Vice President of the Sheikh Zayed Institute, who leads the Image Guided Non-Invasive Therapeutic Energy (IGNITE) program.

IGNITE is a joint clinical and research collaboration between the Sheikh Zayed Institute and the Divisions of Radiology, Oncology, Surgery, and Anesthesiology at Children’s National. MR-HIFU is also being used to treat pediatric refractory soft tissue tumors, a first-in-the-world clinical trial that is a collaboration between Children’s National and the NIH Center for Interventional Oncology directed by Bradford Wood, MD. Additionally, the IGNITE team has started preliminary work to explore applications of MR-HIFU for noninvasive ablation of growth plates and pediatric solid tumors.

In addition to Drs. Sharma and Kim, the team for the ablation of osteoid osteoma clinical trial includes: AeRang Kim, MD, PhD, pediatric oncologist; Matthew Oetgen, M.D., Division Chief of Orthopaedic Surgery and Sports Medicine; Kaleb Friend, M.D., pediatric orthopedic surgeon; Pavel Yarmolenko, Ph.D., Haydar Celik, Ph.D., and Avinash Eranki, biomedical engineers; Viktoriya Beskin, MR technologist; and Janish Patel, M.D., and Domiciano Santos, M.D., pediatric anesthesiologists.

Study to evaluate heat-activated chemotherapy drug

Children’s National Health System and Celsion Corp., a leading oncology drug-development company, will be the first to launch a clinical study in the U.S. that evaluates the use of ThermoDox®, a heat-activated chemotherapy drug, in combination with noninvasive magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) to treat refractory or relapsed solid tumors in children and young adults.

The investigator-sponsored Phase I study, which is partially funded by an NIH R01 grant, will determine a safe and tolerable dose of ThermoDox, a lyso-thermosensitive liposomal doxorubicin (LTLD), which can be administered in combination with MR-HIFU. Under the guidance of an MRI, the high-intensity focused ultrasound directs soundwave energy to heat the tumor and the area around the tumor. When heated, the liposome rapidly changes structure and releases doxorubicin directly into and around the targeted tumor.

“There is currently no known cure for many patients with refractory recurring solid tumors, despite the use of intensive therapy, so we need to identify new, smarter therapies that can improve outcomes,” said AeRang Kim, M.D., Ph.D., oncologist and member of the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, who is also principal investigator for the study. “Recent advances in the use of noninvasive MR-HIFU coupled with novel therapies, such as LTLD, may provide us with a mechanism to noninvasively administer high concentrations of the drug directly to the site where it is most needed and avoid toxicity to other areas of the body.”

A First to Treat Childhood Cancer

This is the first time LTLD is being combined with MR-HIFU and the first time it is being evaluated in children.

“Celsion’s experience in combining ThermoDox with HIFU, a noninvasive next generation heating technology, supports this very important research in childhood cancers. From a safe dose, ThermoDox’s proven ability to deliver high concentrations of an effective chemotherapy directly to a heated tumor makes it an ideal candidate for a trial involving children and young adults,” said Michael H. Tardugno, Celsion’s chairman, president and CEO. “This study will further elucidate ThermoDox’s potential in combination with ultrasound-induced hyperthermia, and highlight potential applications of ThermoDox in combination with a broad range of heating technologies that could address an even larger population of patients.”

A Multidisciplinary Approach

The study targeting the treatment of childhood sarcomas will be carried out as a multidisciplinary collaboration between Children’s National, Celsion, and Dr. Bradford Wood’s team at the National Institutes of Health.

This is the latest study from the Image-Guided Non-Invasive Therapeutic Energy (IGNITE) program, a collaboration of the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National and the pediatric health system’s Divisions of Radiology, Oncology, Surgery, and Anesthesiology. The goal of the IGNITE program is to improve the quality of life and outcomes for pediatric patients through the development and clinical introduction of novel minimally invasive and noninvasive surgery technologies and combination therapy approaches. In 2015, doctors from Children’s National were the first in the U.S. to treat osteoid osteoma, a benign and painful bone tumor, using MR-HIFU.

ThermoDox is currently in late-stage clinical trials in primary liver cancer and recurrent chest wall breast cancer. It is positioned for use with multiple heating technologies, and has the potential for applications in the treatment of other forms of cancer including metastatic liver and nonmuscle invading bladder cancers.

Cancer update: tumor targeting, neurofibromatosis type 1 symptoms

June 6, 2016Targeting tumors more precisely, with fewer lasting side effects for kids
Pediatric patients with cancer are often treated with a cocktail of therapies to attack the disease through a variety of mechanisms. While this approach has been instrumental in saving children’s lives, the life-saving therapies can be accompanied by acute side effects, and the treatments may have lingering impacts as cancer survivors enter adulthood. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) holds the promise of surgically removing large tumors without exacting the same array of harsh side effects. Ultrasound relies on high-frequency sound waves to make diagnostic images, and those same sound waves can be used therapeutically to destroy tumors. Layering on MR imaging gives clinicians the ability to precisely guide the ultrasound therapy in real time. A study led by Children’s National Health System researchers and clinicians is using MR-HIFU for the first time in children to examine its safety and feasibility.

May 11, 2016 – Quantitative MRI criteria for optic pathway enlargement in neurofibromatosis type 1
Symptoms of neurofibromatosis type 1 (NF1) vary widely, but the condition is characterized by changes in skin pigmentation and growth of tumors along nerves. The research team sought to determine quantitative size thresholds for enlargement of the optic nerve, chiasm, and tract in children aged 0.5 to 18.6 years with NF1. The study, published in Neurology, found that quantitative reference values for anterior visual pathway enlargement will enhance development of objective diagnostic criteria for optic pathway gliomas secondary to NF1.