Cancer

Winners of the International Conference on Medical Image Computing and Computer Assisted Intervention

AI team wins international competition to measure pediatric brain tumors

Winners of the International Conference on Medical Image Computing and Computer Assisted Intervention
Children’s National Hospital scientists won first place in a global competition to use artificial intelligence (AI) to analyze pediatric brain tumor volumes, demonstrating the team’s ground-breaking advances in imaging and machine learning.

During the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), the Children’s National team demonstrated the most accurate algorithm to study the volume of brain tumors – the most common solid tumors affecting children and adolescents and a leading cause of disease-related death at this young age. The technology could someday help oncologists understand the extent of a patient’s disease, quantify the efficacy of treatments and predict patient outcomes.

“The Brain Tumor Segmentation Challenge inspires leaders in medical imaging and deep learning to try to solve some of the most vexing problems facing radiologists, oncologists, computer engineers and data scientists,” said Marius George Linguraru, D.Phil., M.A., M.Sc., the Connor Family Professor in Research and Innovation and principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation. “I am honored that our team won, and I’m even more thrilled for our clinicians and their patients, who need us to keep moving forward to find new ways to treat pediatric brain tumors.”

Why we’re excited

With roughly 4,000 children diagnosed yearly, pediatric brain tumors are consistently the most common type of pediatric solid tumor, second only to leukemia in pediatric malignancies. At the urging of Linguraru and one of his peers at the Children’s Hospital of Philadelphia, pediatric data was included in the international competition for the first time, helping to ensure that children are represented in medical and technological advances.

The contest required participants to use data from multiple institutions and consortia to test competing methods fairly. The Children’s National team created a method to tap into the power of two types of imaging and machine learning: 3D convolutional neural network and 3D Vision Transformer-based deep learning models. They identified regions of the brain affected by tumors, made shrewd data-processing decisions driven by the team’s experience in AI for pediatric healthcare and achieved state-of-the-art results.

The competition drew 18 teams who are leaders from across the AI and machine learning community. The runner-up teams were from NVIDIA and the University of Electronic Science and Technology of China.

The big picture

“Children’s National has an all-star lineup, and I am thrilled to see our scientists recognized on an international stage,” said interim Executive Vice President and Chief Academic Officer Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer for Immunology Research. “As we work to attack brain tumors from multiple angles, we continue to show our exceptional ability to create new and better tools for diagnosing, imaging and treating these devastating tumors.”

Patient and doctor demoing Rare-CAP technology

M.D. in your pocket: New platform allows rare disease patients to carry medical advice everywhere

When someone has a rare disease, a trip to the emergency room can be a daunting experience: Patients and their caregivers must share the particulars of their illness or injury, with the added burden of downloading a non-specialist on the details of a rare diagnosis that may change treatment decisions.

Innovators at Children’s National Hospital and Vanderbilt University Medical Center, supported by Takeda, are trying to simplify that experience using a new web-based platform called the Rare Disease Clinical Activity Protocols, or Rare-CAP. This revolutionary collection of medical information allows patients to carry the latest research-based guidance about their rare disorders in their phones, providing a simple QR code that can open a trove of considerations for any medical provider to evaluate as they work through treatment options for someone with an underlying rare disease.

“No one should worry about what happens when they need medical help, especially patients with rare diseases,” said Debra Regier, M.D., division chief of Genetics and Metabolism at Children’s National and Rare-CAP’s lead medical advisor. “We built this new tool because I have watched as my patient-families have wound up in an emergency room — after all, kids get sprains or fractures — but they don’t have the expertise of a rare disease specialist with them. My hope is that they’re going to pull out their phones and access Rare-CAP, which will explain their rare disease to a new provider who can provide more thoughtful and meaningful care.”

The big picture

A rare disease is defined as any disorder that affects less than 200,000 people in the United States. Some 30 million Americans are believed to be living with one of the 7,000 known rare disorders tracked by the National Organization of Rare Diseases (NORD). Led by Dr. Regier, the Rare Disease Institute at Children’s National is one of 40 NORD centers for excellence in the country that provide care, guidance and leadership for the wide array of disorders that make up the rare disease community.

While a key goal of Rare-CAP is to bolster patient self-advocacy, the platform will also allow medical providers to proactively search for protocols on rare diseases when they know they need specialized advice from experts at Children’s National, a network of tertiary care centers and patient organizations.

As a leading values-based, R&D-driven biopharmaceutical company, Takeda has committed $3.85 million to the project to help activate meaningful change and empower a brighter future for rare disease communities, providing a unique understanding of the struggle that patients and caregivers face when they need care.

“Our team, alongside the medical and rare disease community, saw the need for a single portal to collect standardized care protocols, and we are thrilled to see this innovative tool come to life,” said Tom Koutsavlis, M.D., head of U.S. Medical Affairs at Takeda. “People with rare diseases and their caregivers need faster access to authoritative medical information that providers anywhere can act on, this will lead to improving the standard of care, accelerating time to diagnosis and breaking down barriers to increase equitable access.”

The patient benefit

The creators of Rare-CAP imagined its use in a wide range of settings, including emergency rooms, surgical suites, dental offices, urgent care offices and school clinics. The platform will eventually profile thousands of rare diseases and lay out the implications for care, while also creating a dynamic conversation among users who can offer updates based on real-world experience and changes in medical guidance.

“Our patients are unique, and so is this tool,” Dr. Regier said. “As we roll out Rare-CAP, we believe it is just the beginning of the conversation to expand the platform and see its power for the patient and provider grow, with each entry and each new rare disease that’s added to the conversation.”

Drs. Robert Keating, Brian Rood and Catherine Bollard

Children’s National announces new professorships

Drs. Robert Keating, Brian Rood and Catherine Bollard

Robert Keating, M.D., Brian Rood, M.D., and Catherine Bollard, M.D., M.B.Ch.B.

Children’s National Hospital named Robert Keating, M.D., as the McCullough Distinguished Professor of Neurosurgery. He serves as the chief of neurosurgery and co-director of the high-intensity focused ultrasound (HIFU) program at Children’s National.

Children’s National Hospital named Brian Rood, M.D., as the Kurt D. Newman, M.D., Professor of Neuro-Oncology. He serves as director of clinical neuro-oncology and medical director of the Brain Tumor Institute at Children’s National.

Children’s National Hospital elevated Catherine Bollard, M.D., M.B.Ch.B., to the Dr. Robert J. and Florence T. Bosworth Distinguished Professor of Cancer and Transplantation Biology Research. She is the Interim Executive Vice President and Chief Academic Officer and Interim Director, Children’s National Research Institute. She also serves as the director of the Center for Cancer and Immunology Research and director of the Program for Cell Enhancement and Technologies for Immunotherapy at Children’s National.

About the awards

Professorships at Children’s National support groundbreaking work on behalf of children and their families and foster new discoveries and innovations in pediatric medicine. These appointments carry prestige and honor that reflect the recipient’s achievements and donor’s forethought to advance and sustain knowledge. Children’s National is grateful for its generous donors, who have funded 47 professorships.

Dr. Keating is a longstanding leader in neurosurgery research and care. His areas of expertise include brain tumors, traumatic brain injuries, craniofacial anomalies, Chiari malformations and spinal dysraphism. With Dr. Keating’s leadership, the neurosurgery department is pioneering innovations such as HIFU, a non-invasive therapy using focused ultrasound waves to ablate a focal area of tissue. It can treat tumors located in difficult locations of the brain, movement disorders and epilepsy. Children’s National was one of the first pediatric hospitals in the nation to use HIFU for neuro-oncology patients.

“Our goal is to elevate our top-ranked program to even greater heights,” says Dr. Keating. “We will continue to use cutting-edge technology and non-invasive approaches to make the knife obsolete in pediatric neurosurgery and improve outcomes for children.”

Dr. Rood studies the biology of pediatric brain tumors. He focuses on protein signatures and biomarkers specific to different types of brain cancers. His study of neoantigens is informing the development of T-cell immunotherapies to target a tumor’s unique proteins.

“Immunotherapy is revolutionizing how we treat childhood brain tumors — safely, effectively and with the precision made possible by using a patient’s own cells,” says Dr. Rood. “This professorship enables our team to advance this revolution, which will save lives and improve lifetimes.”

Dr. Bollard received the Dr. Robert J. and Florence T. Bosworth Professor of Cancer and Transplantation Biology Research in 2018 to support her work to develop cell and gene therapies for patients with cancer and underlying immune deficiencies. Her professorship has been elevated to a distinguished professorship to amplify her research and celebrate her accomplishments in the field of immunotherapy.

About the donor

These appointments were made possible through an extraordinary $96 million investment from an anonymous donor family for rare pediatric brain tumor research and care. It is one of the hospital’s largest donations and will transform the hospital’s ability to give patients with rare brain cancer a better chance at healthy lifetimes.

The anonymous family brings a depth of compassion for children facing rare and often challenging diagnoses. Their partnership will immediately advance every aspect of our globally recognized leadership to create new, more effective treatments.

Their investment also endowed the Professorship in Molecular Neuropathology. We look forward to bestowing that honor on a Children’s National pediatric leader.

model of the brain

A new way to treat pediatric gliomas with BRAF V600 mutations

model of the brain

Gliomas account for 45% of all pediatric tumors of the central nervous system.

Gliomas, which can be classified according to histologic grade as high or low grade, account for 45% of all pediatric tumors of the central nervous system. Detection of the BRAF V600E mutation in pediatric low-grade glioma has been associated with a lower response to standard chemotherapy. In previous trials, dabrafenib (both as monotherapy and in combination with trametinib) has shown efficacy in recurrent pediatric low-grade glioma with BRAF V600 mutations, findings that researchers found warrant further evaluation of this combination as first-line therapy.

The big picture

In a recent study published in the New England Journal of Medicine, experts found that among a randomized cohort of 110 children with low-grade glioma with BRAF V600 mutations, dabrafenib plus trametinib resulted in significantly more responses, longer progression-free survival and a better safety profile than standard chemotherapy as first-line therapy.

“For the past 20 to 30 years, the only effective safe therapy was chemotherapy. In older children, radiation can also be effective, but there’s reluctance on using radiation on a developing brain,” said Roger Packer, M.D., director of the Brain Tumor Institute at Children’s National Hospital and co-author of the study. “As we learned the specific molecular genetic makeups of these tumors, either high- or low-grade gliomas, we found it to be effective to use molecular therapies. These are safer and more effective than chemotherapy alone.”

Dr. Packer also added that there’s approval from the FDA, proving that the industry sees value in investing in pediatrics.

Why it matters

This randomized trial shows the superiority of dabrafenib plus trametinib as a first systemic therapy for pediatric patients with low-grade glioma with BRAF V600 mutations as compared with carboplatin plus vincristine, the standard chemotherapy approach. This benefit was evident in the higher independently determined response, longer progression-free survival and better side-effect profile as reflected in the lower frequency of treatment discontinuation because of toxicity.

“Children treated with a molecular targeted therapy could safely tolerate the therapy and had better outcomes than children who were treated with chemotherapy,” Dr. Packer added.

Overall, these findings show the value of early molecular testing in children with low-grade glioma to determine the presence or absence of BRAF V600 mutations.

You can read the full study “Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations” here.

Sickle Cell Anemia 3D Illustration

New telemedicine-based behavioral intervention program eases pain of patients with SCD

Sickle Cell Anemia 3D Illustration

Telemedicine-based behavioral interventions can reduce pain-related functional impairment in youth with SCD.

Sickle cell disease (SCD) pain is often associated with functional impairment and treatment is often limited to pharmacological approaches with unwanted side effects. Behavioral interventions are common for non-SCD pain populations, but interventions designed to address pain-related impairment in SCD are lacking.

In a recent study published in Pediatric Blood & Cancer, researchers conducted a pilot of a 4-week behavioral pain intervention for youth with SCD delivered via telemedicine known as the Balance Program.

Using an innovative combination of cognitive-behavioral therapy and acceptance-based approaches, researchers found that the intervention was feasible, evidenced by youth and caregiver ratings of high acceptability and satisfaction and excellent treatment completion rates. In addition, youth and their caregivers both reported significant reductions in the degree to which SCD pain interfered with daily activities after the treatment.

What’s been the hold-up in the field?

Researchers and clinicians know that there is a strong psychological component to all experiences of pain and there has been growing evidence in recent decades regarding the effectiveness of behavioral therapies for reducing pain and improving functioning.

“However, sickle cell disease presents unique challenges because unlike many pain presentations, it is common for patients with sickle cell disease to experience both acute and chronic pain, making treatment recommendations less clear,” said Megan Connolly, Ph.D., psychologist at Children’s National Hospital and the study’s lead author. “Previous studies have rarely focused on reducing pain-related disability, which is important for optimizing quality of life.”

How does this work move the field forward?

This study demonstrated the feasibility and acceptability of a telemedicine-based behavioral intervention to reduce pain-related functional impairment in youth with SCD. Nearly all youth and their caregivers rated the intervention as moderately or highly acceptable and 90% of patients completed the full treatment program.

“Moreover, the Balance Program resulted in significant reductions in the extent to which sickle cell disease pain interfered with daily activities,” Dr. Connolly added.

What about the findings is exciting?

This research explains what experts can be doing to reduce the impact of pain on the lives of children and adolescents with SCD. Through their findings, researchers learned that a telemedicine-based behavioral pain intervention, which is often more convenient for families than traveling to the hospital for weekly visits, can meaningfully reduce the impact of pain on daily living.

“It is one thing to develop a program that you think will be helpful, but it’s another thing to develop a program that families will be interested in and doesn’t add unnecessary stress to their lives,” Dr. Connolly said. “Although this study had a relatively small sample, I was also excited to see the magnitude of improvements in pain-related impairment, which was quite large. We plan to continue refining this treatment based on patient and caregiver feedback and looking for ways to increase accessibility to these types of treatments for sickle cell disease pain.”

little girl with cancer

A destination for pediatric oncology care: Children’s National Hospital’s T-cell therapy trials

When children are diagnosed with pediatric cancer, most doctors are forced to reach for the same standard therapies that were available decades ago. Research oncologists at Children’s National Hospital are changing that with clinical trials that will hopefully train the body’s immune system – specifically its T cells – to fight the tumors.

Holly Meany, M.D., and her colleague Amy Hont, M.D., oncologists and research scientists at the Center for Cancer and Immunology Research, have put together a pair of clinical trials that are investigating two pathways for using T cells to go after solid tumors.

“At Children’s National, we have a novel immunotherapy to offer to patients with relapsed or refractory solid tumors,” said Meany, director of the Solid Tumor Program. “This is a patient population who has failed standard therapy, so new technologies and treatments are always needed in this group.”

Where we started

Meany’s trial laid the foundation. She began the center’s research using a patient’s own blood sample to develop a targeted therapy and evaluate the safety and efficacy of this approach. In her study, scientists isolated the T cells, grew millions in a lab and reinfused them into the patient. The cells were replicated in an environment that was rich in three proteins that are commonly found on the surface of solid tumor cancer cells.

“Our hope and hypothesis are that when we give the T cells back to the patient, those T cells circulate and hunt down the cancer cells that have the tumor proteins,” Meany said. “We are hoping to use the patient’s own immune system to attack the cancer in an enduring way.”

Where we are headed

Hont’s phase 1 trial, which is currently recruiting participants, builds on Meany’s work using a healthy donor whose T cells have not been impacted by chemotherapy or other treatments. The cells can be prepared, stored and readily available for patients who need them. They are also matched through specific proteins on the patient’s own cells to bolster their effectiveness. The participants in this trial have Wilms tumors, rhabdomyosarcoma, neurosarcoma, soft tissue sarcoma or neuroblastoma, but conventional therapies including chemotherapy, radiation or surgery were unable to fully treat the disease.

In both studies, Hont said that the T cells have been given in an outpatient setting with fewer side effects compared to other cancer treatments aimed at high-risk malignancies.

“This allows patients to really maintain a good quality of life during a particularly hard time,” Hont said. “Also, these T cells are designed to act in the body the way that our immune system acts in a physiologic way. This means patients typically don’t have the severe side effects that we think of with chemotherapy or other therapies.”

Children’s National leads the way

The team at Children’s National is one of the few in the country to offer this kind of T-cell therapy for solid tumors. “Immunotherapy has been challenging for this patient population because the tumors are adept at finding out ways to evade treatment,” Hont said. “Giving patients a chance to receive a targeted T-cell therapy, while also maintaining a high quality of life, is something that’s special here.”

illustration of a nuclesome

Researchers publish first-ever atlas of cancerous mutations in histones

Leading genetic researchers at Children’s National Hospital have published the first pan-cancer atlas of key mutations that can drive molecular changes leading to tumors, creating a roadmap that could lead to new treatments for brain tumors and other cancers.

The research – published in npj Genomic Medicine – presents the first-of-its-kind atlas of histone mutations across pediatric, adolescent/young adult and adult cancers. The novel genetic work offers a framework allowing specific cancers to be redefined in the context of changes in histones, which are essential proteins that provide the structural support for chromosomes.

The big picture

“One of the major challenges that we face every day with pediatric, aggressive tumors, including pediatric high-grade gliomas, is that these tumors grow fast. Doctors often have to give patients 9 to 12 months from diagnosis,” said Javed Nazarian, Ph.D., scientific director of the Brain Tumor Institute at Children’s National and principal investigator at the Center for Genetic Medicine Research. “Children’s National has put together a team of clinicians that are truly devoted to finding a therapy for pediatric high-grade gliomas and aggressive pediatric brain tumors. Our dedicated team empowers translational research, from bench to bedside and reverse translation.”

In 2023, the American Cancer Society estimates that 9,910 children under age 15 will be diagnosed with cancer, making it the second leading cause of death among children. Because of treatment advances, 85% will survive, but many will be left with lifelong disabilities from their treatment. Nazarian and his team believe that identifying the underlying molecular alterations leading to cancers will be essential to finding new therapies that extend life expectancies and preserve quality of life.

The fine print

Histones are essential cellular structures, which prevent DNA from getting tangled. Nazarian and other researchers are investigating whether errors in histones could lead to cancers, including high-grade gliomas and other particularly sinister tumors that can strike young children. By mapping the mutations of the histone-encoding genes, Nazarian and his team believe they can find the drivers of tumors in many pediatric and adult cancers. In studying more than 12,000 tumors for the pan-cancer atlas, they cataloged patient ages, survival outcomes and tumor locations to reveal important trends among different cancers.

Overall, the team found that 11% of tumors had somatic histone mutations, with the highest rates observed among chondrosarcoma, a type of bone cancer (67%); pediatric high-grade glioma, a type of cancer that attacks glial cells in the brain and spinal cord (>60%); and lymphoma, a category of cancers in the lymph system (>30%).

“I think one implication of our study is that we are looking at the epigenomic changes of these mutations in a new light,” Nazarian said. “These mutations are not just specific to a particular tumor type, but they are indeed across a large spectrum of cancer types, and they come in different flavors that could potentially show a new avenue for treatments.”

Eugene Hwang

Eugene Hwang, M.D., appointed chief of Oncology

Eugene Hwang

Dr. Hwang has been part of the Children’s National team for 13 years and most recently served as the associate chief of Oncology.

Eugene (Gene) Hwang, M.D., has been appointed to the role of chief of Oncology at Children’s National Hospital.

Dr. Hwang has been part of the Children’s National team for 13 years and most recently served as the associate chief of Oncology.

“I joined the division in 2010, fairly new to the job and hoping to simply learn how to treat pediatric cancer. Thirteen years later, I have learned from an almost overwhelming number of people – colleagues, mentors, patients and their families,” Dr. Hwang said. “Our field constantly reminds us of the urgent need for better treatments; in pursuit of that goal, the program at Children’s National has innovated at a level which has taught me the importance of translational and clinical research, connections within our team and the community, and above all, our commitment to our patients. I am honored and excited to help lead this team to continue in their mission to cure more children of their cancer and with fewer side effects.”

Dr. Hwang received his degree in cell and molecular biology from Rice University and a medical degree from Duke University. He completed a pediatrics residency at Brown University/Hasbro Children’s Hospital and returned to Duke for fellowships in pediatric hematology/oncology and pediatric neuro-oncology.

Since Dr. Hwang joined Children’s National in 2010, he has risen to international prominence for his expertise in pediatric brain tumors. Dr. Hwang holds study leadership roles in several research consortia, including the Children’s Oncology Group (COG), Pediatric Brain Tumor Consortium (PBTC), Collaborative Network for Neuro-Oncology Clinical Trials (CONNECT), Pediatric Neuro-Oncology Consortium (PNOC) and the Collaborative Ependymoma Research Network (CERN).

At Children’s National, he serves as principal investigator for two investigator-initiated studies and is the recipient of a Department of Defense IMPACT grant, the collaborative awardee on multiple NIH grants, and numerous foundation grants.  He has served on several of our clinical and scientific committees, such as director of neuro-oncology fellowship program and vice chair of Children’s National Brain Tumor Institute. In addition, Dr. Hwang was recently installed as the inaugural William Seamus Hughes Professor of Neuro-oncology and Immunology.

“The division already has established itself as one of the premier pediatric oncology programs in the world,” Dr. Hwang added. “Being able to offer an even more cutting-edge therapy so that every child treated at Children’s National has the ability to access world-class treatment is a primary goal of our division and I hope to see our team extend its reach of transformative treatments for more children with cancer.”

Microscopic view of thalassemia

What it means to be a designated treatment center for beta thalassemia

Microscopic view of thalassemia

ZYNTEGLO® (betibeglogene autotemcel) is an FDA-approved gene therapy for transfusion-dependent beta thalassemia, which is an inherited blood disorder that causes the body to make less hemoglobin, resulting in anemia.

Children’s National Hospital is a designated qualified treatment center for Beta Thalassemia Gene Therapy. ZYNTEGLO® (betibeglogene autotemcel) is an FDA-approved gene therapy for transfusion-dependent beta thalassemia, which is an inherited blood disorder that causes the body to make less hemoglobin, resulting in anemia.

This unique therapy is made specifically for each child or adult, by adding functional copies of the beta-globin gene to their own blood stem cells. Most patients with beta thalassemia who have received a one-time ZYNTEGLO® treatment have been able to produce sufficient hemoglobin because of the treatment, freeing them from regular blood transfusions.

Evelio Perez, M.D., and Robert Nickel, M.D., lead the gene therapy program and discuss the importance of offering this gene therapy to patients with beta thalassemia.

Q: What has been the hold-up in this field and how does this work move the field forward?

A: Stem cell transplant using a donor’s cells (called allogeneic transplant) has been a curative treatment option for patients with beta thalassemia for many years. Unfortunately, many patients do not have a suitable donor. And, even for patients who have a donor, allogenic transplants have serious risks including a problem called graft versus host disease (GVHD) in which the new donor cells attack the patient’s body. Gene therapy like ZYNTEGLO® has no risk of GVHD because we use the patient’s own cells.

Q: How will this benefit patients? What excites you most about this advancement?

A: This treatment will give almost every patient with beta thalassemia the option of undergoing curative therapy. This is obviously exciting for patients because it means they no longer need to come to the hospital every 3-4 weeks for transfusions as well as take medications to treat the dangerous accumulation of iron in their body. It is also good for the health system because it will allow donated blood to go to other patients in need.

Q: How is Children’s National leading in this space?

A: This therapy really requires a multi-disciplinary team including members of the transplant, hematology, apheresis, stem cell lab and others! At Children’s National we have the experts on these teams and experience working together. As one of the largest sickle cell disease centers in the country, we are participating in research to hopefully help bring gene therapy to patients with sickle cell disease in the near future too.

child in hospital bed

$96 million philanthropic investment will transform rare pediatric brain tumor research and care

child in hospital bedChildren’s National Hospital announced a $96 million investment from an anonymous donor family to transform rare childhood brain tumor research and care. The donation, which strengthens our globally recognized leadership in the field, is one of the largest in the hospital’s history.

Children’s National will harness the investment to recruit more top talent and advance the most promising research. This will produce safer, more effective treatments. It also will elevate standards of care to help children with rare brain tumors thrive for a lifetime.

The big picture

Brain tumors are the most common solid tumors affecting children. They are especially challenging in kids because their brains are still developing. The disease and current treatments can put them at risk for lifelong complications.

The anonymous family’s investment provides new hope for patients who face rare and often challenging brain tumor diagnoses — in the Washington, D.C., community and around the world.

“This incredible partnership will lift up one of the nation’s top pediatric brain tumor programs into the stratosphere,” said Kurt Newman, M.D., president and CEO of Children’s National. “It will immediately propel our best-in-class research and care, allowing us to bring new therapies to children with brain tumors. This fundamentally changes the healthcare journey and long-term outcomes for children and their families.”

Why it’s important

This transformational investment will have a far-reaching impact on our ability to save and improve the lives of children with brain tumors. Funds will fuel collaborative breakthroughs across a range of scientific and psychosocial approaches.

The partnership will supercharge highly individualized and promising treatments for children with brain tumors. We will radically transform the research landscape with a focus on:

  • Low intensity focused ultrasound (LIFU) – Advancing laboratory research and a clinical program designed to treat childhood brain tumors with LIFU therapy
  • Cellular immunotherapy – Testing new gene-engineered immune cell products and accelerating their integration into standards of care
  • Rare Brain Tumor Program – Propelling new clinical trials through the hospital’s national and global leadership in pediatric brain tumor consortia. Already, Children’s National is leading a new collaborative with hospitals in North America, South America and Europe to better understand and find novel treatments for these rare diseases
  • Neurosurgery innovation – Exploring multiple ways to perform safer, more effective neurosurgery and developing new methods to enhance drug/agent delivery
  • Precision medicine – Recruiting leading scientists to advance biology-informed therapies that can be targeted for children across a spectrum of brain tumors
  • Good Manufacturing Practices (GMP) facility – Expanding our GMP, one of the first standalone facilities at a children’s hospital in the country, to translate new discoveries into clinical trials more rapidly
  • Additional priorities including expansion of clinical research infrastructure and growth of bioinformatics, brain tumor repository and molecular diagnostics initiatives

The partnership also transforms how we approach care. It will power our pursuit of psychosocial, behavioral health and neuroscientific initiatives to help kids live well and cope with the unique circumstances of their diagnosis. We will focus on:

  • Lifetime health and wellness – Building a world-class research and clinical care program to shape a new paradigm for supporting a child’s physical and emotional health during and long after cancer treatment
  • Child Mental Health & Behavioral Brain Tumor Lab – Establishing a robust neuro-oncology mental health program that delivers timely interventions and specialized psychiatric care for patient well-being
  • Additional priorities including a new Neuroscience Nursing Excellence Program and growth of psychosocial support activities that bring comfort and encouragement to children during their treatment journey

Children’s National is proud to lead the way to a better future for pediatric rare brain tumor patients and expand our internationally recognized capabilities for neuro-oncology care.

U.S. News Badges

Children’s National Hospital ranked #5 in the nation on U.S. News & World Report’s Best Children’s Hospitals Honor Roll

U.S. News BadgesChildren’s National Hospital in Washington, D.C., was ranked #5 in the nation on the U.S. News & World Report 2023-24 Best Children’s Hospitals annual rankings. This marks the seventh straight year Children’s National has made the Honor Roll list. The Honor Roll is a distinction awarded to only 10 children’s hospitals nationwide.

For the thirteenth straight year, Children’s National also ranked in all 10 specialty services, with eight specialties ranked in the top 10 nationally. In addition, the hospital was ranked best in the Mid-Atlantic for neonatology, cancer, neurology and neurosurgery.

“Even from a team that is now a fixture on the list of the very best children’s hospitals in the nation, these results are phenomenal,” said Kurt Newman, M.D., president and chief executive officer of Children’s National. “It takes a ton of dedication and sacrifice to provide the best care anywhere and I could not be prouder of the team. Their commitment to excellence is in their DNA and will continue long after I retire as CEO later this month.”

“Congratulations to the entire Children’s National team on these truly incredible results. They leave me further humbled by the opportunity to lead this exceptional organization and contribute to its continued success,” said Michelle Riley-Brown, MHA, FACHE, who becomes the new president and CEO of Children’s National on July 1. “I am deeply committed to fostering a culture of collaboration, empowering our talented teams and charting a bold path forward to provide best in class pediatric care. Our focus will always remain on the kids.”

“I am incredibly proud of Kurt and the entire team. These rankings help families know that when they come to Children’s National, they’re receiving the best care available in the country,” said Horacio Rozanski, chair of the board of directors of Children’s National. “I’m confident that the organization’s next leader, Michelle Riley-Brown, will continue to ensure Children’s National is always a destination for excellent care.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals and recognizes the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News.

“For 17 years, U.S. News has provided information to help parents of sick children and their doctors find the best children’s hospital to treat their illness or condition,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “Children’s hospitals that are on the Honor Roll transcend in providing exceptional specialized care.”

The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.

The eight Children’s National specialty services that U.S. News ranked in the top 10 nationally are:

The other two specialties ranked among the top 50 were cardiology and heart surgery, and urology.

Germ cell tumor of testicle under microscopy

New research: Genes that drive testicular cancer identified

In the largest sequencing study to date on testicular cancer, researchers at Children’s National Hospital have identified genes that contribute to testicular germ cell tumors (TGCT), the most common cancer among young, white men.

The findings, published in European Urology, provide direction for future screening and treatment of this disease, which can strike during the teen years and often runs in families. While treatable when identified early, testicular cancer leads to infertility, mental health issues and sometimes death, making its identification crucial for young adults.

“Testicular cancer is really a young person’s disease,” said Louisa Pyle, M.D., Ph.D. , a pediatrician, medical geneticist and research geneticist at the Children’s National Rare Disease Institute. “Most folks who have testicular cancer are between the ages of 15 and 45. Even though testicular cancer is relatively rare in the cancer world, it results in the greatest number of years lost among all adult cancers.”

What we hope to discover

Dr. Pyle led a research team that included experts at the National Cancer Institute and the University of Pennsylvania to study families with multiple members diagnosed with testicular cancer. They used whole exome sequencing to identify variants in many genes that predisposed patients to TGCT. Their work suggests that multiple variants – inherited together – increased the risk for the disease and provides potential routes for drugs that could be used for prevention and treatment.

“We found many genes that help us understand how testicular cancer happens,” Dr. Pyle said. “Our hope is that we can use that to try to come up with better treatments or better ways to preserve fertility for people with testicular cancer or gonadal differences.”

The patient benefit

Testicular cancer most often strikes men of European ancestry. It is also more common among intersex patients and those with differences in sex development, which is a clinical and research focus for Dr. Pyle. Medically, these are children who have a change in the biological characteristics of sex, including their chromosomes, hormones, gonads or physical body parts.

By studying a more common version of testicular cancer, the team learned about the underlying genetics in a way that will benefit intersex patients.

“One of the things we do in medicine is study a common version of the rare thing,” Dr. Pyle said.  “Through this research, we learned that the same genes that cause intersex traits in some patients are also changed in subtle ways for people with testicular cancer. This is a way to study something that could improve care for those kids, by studying a group that has greater numbers.”

Eugene Hwang

Eugene Hwang, M.D., named as William Seamus Hughes Professor of Neuro-oncology and Immunology

Eugene HwangChildren’s National Hospital named Eugene Hwang, M.D., the inaugural William Seamus Hughes Professor of Neuro-oncology and Immunology. This professorship is the first at Children’s National to focus exclusively on these two pediatric specialties.

Dr. Hwang serves as associate chief of oncology, director of the Clinical Neuro-oncology Immunotherapeutics Program and director of the Neuro-oncology Fellowship Program. He is an associate professor of pediatrics at the George Washington University School of Medicine and Health Sciences.

About the award

Dr. Hwang joins a distinguished group of 42 Children’s National physicians and scientists who hold an endowed chair. Professorships at Children’s National support groundbreaking work on behalf of children and their families and foster new discoveries and innovations in pediatric medicine. These appointments carry prestige and honor that reflect the recipient’s achievements and donor’s forethought to advance and sustain knowledge.

Dr. Hwang has dedicated much of his career to the pursuit of new therapies that improve outcomes for children with brain cancer. He has led many early phase clinical trials on immunotherapeutics, gene therapy and new targeted agents. He participates in international studies focused on reducing harmful side effects of standard treatments. He serves as the principal investigator for the Pediatric Brain Tumor Consortium and co-chairs their Immunotherapy Working Group. Dr. Hwang also lends his time to grant review committees and the scientific advisory boards of several large foundations.

Claire and Kevin Hughes, through their vision and generosity, are ensuring that Dr. Hwang and future holders of this professorship will launch new initiatives to rapidly advance the fields of pediatric neuro-oncology and immunotherapy, elevate our leadership and improve outcomes for children diagnosed with brain cancer.

About the donors

Claire and Kevin Hughes established this professorship with support from community partners in loving memory of their son William Seamus Hughes (Willie). Their dedication to giving all children a chance for life has helped launch groundbreaking trials and research at Children’s National, including one of the first trials in the U.S. to use cell therapy to treat brain tumors.

“Working with Willie meant working with a young man who embodied a resilient, cheerful spirit that was truly remarkable,” said Dr. Hwang. “It meant fighting side-by-side with a walking inspiration, who I continue to remember and who continues to drive the mission of curing childhood brain cancer. I’m deeply honored to ensure that Willie’s spirit and bravery lives on in the promise to other families that face a devastating brain tumor diagnosis.”

illustration of a brain's neural activity

Debuting sonodynamic therapy with ALA to treat rare brain tumors

illustration of a brain's neural activity

Preclinical studies show that guided focused ultrasound and ALA can slow growth of gliomas and extend survival.

Children’s National Hospital is conducting a first-in-human study of aminolevulinic acid (ALA) sonodynamic therapy (SDT) for diffuse intrinsic pontine glioma (DIPG).

Preclinical studies led by experts at Children’s National have shown that SDT through MR guided focused ultrasound (MRgFUS) to activate protoporphyrin IX (PpIX), an ALA, can slow growth of gliomas and extend survival in animal models.

In a recently published technical communication in the Journal of Neuro-Oncology, the authors briefly detail the rationale and mechanism behind the use of SDT using ALA for DIPG, review criteria for patient inclusion, and describe the first patient selected for this clinical trial.

“Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain tumor that occurs in children between 2 and 9 years of age,” writes Hasan Syed, M.D., co-director of the Focused Ultrasound Program at Children’s National and lead author of the findings. “Despite standard therapy, prognosis remains poor with an average survival of 9–12 months after diagnosis.”

Future procedures will involve ascending drug and low-intensity focused ultrasound (LIFU) energy dose combinations with evaluations of pharmacokinetics and radiographic evidence of tumor physiological changes.

Dr. Catherine Bollard webinar screen grab

In the News: The challenges of pediatric clinical trials

Dr. Catherine Bollard webinar screen grab“Pediatric cancer is rare, when you compare it to other forms of cancer, especially adult solid tumors. Often pharma companies are not wanting to fund trials that are exclusively to support a pediatric cancer indication. This is a question that I get asked a lot: How to deal with the so-called ‘valley of death’? … You can successfully complete a phase 1/phase 2 trial, show a safety and efficacy signal, but then lack the funds to get FDA approval. Several of us in the field are looking at other strategies to fill this gap, like forming consortiums and using institutional support.”

Catherine Bollard, M.D., M.B.Ch.B, director of the Center for Cancer and Immunology Research, joined Nature to talk about clinical trials for children, including the significant challenges she and her colleagues face to ensure potentially successful treatments have the funding to make it through the approval process. Learn more about her thoughts on the current landscape for pediatric clinical trials and her work on CAR-T cell therapies in her webinar.

Clumps of sickle cell blocking a blood vessel

Neurocognitive and emotional factors predict hospital visits in children with SCD

 

Clumps of sickle cell blocking a blood vessel

Neurocognitive and emotional factors are predictors of visits children with SCD make to the hospital.

Many children with sickle cell disease (SCD) experience significant pain that often results in trips to the emergency department (ED) or hospitalization. Disease characteristics explain some – but not all – of the variability in pain-related healthcare utilization. In a new study published in Pediatric Blood & Cancer, experts examined the role of neurocognitive functioning and emotional factors in predicting future healthcare visits for pain up to three years later.

The big picture

In the 3-year study of 112 youth with SCD between ages 7-16, researchers found that poorer attentional control and greater emotional distress predicted more ED visits and hospitalizations for pain years later.

Past studies that have pointed to the importance of neurocognitive and emotional factors in the experience of pain have only looked at relationships at a single point in time.

“Those types of studies limit our ability to evaluate the directionality of relationships and consider the implications of neurocognitive functioning and emotional well-being for children’s health as they get older,” said lead author Steven Hardy, Ph.D., director of Psychology and Patient Care Services and psychologist in the Center for Cancer and Blood Disorders (CCBD) at Children’s  National Hospital.

Why it matters

This study advances the understanding of the effects of neurocognitive functioning and emotions on the course of pain and disease morbidity in pediatric SCD.

Additionally, the findings will benefit patients by shedding light on potential intervention targets to support effective pain management.

“It also helps to reframe the conversation around pain and healthcare utilization in SCD by broadening our understanding of the factors that precipitate pain to include neurocognitive functioning and mental health,” Dr. Hardy added.

What’s unique

This work demonstrates that factors beyond disease characteristics are important to consider in a comprehensive approach to managing pain and improving quality of life for children with SCD.

“It shows that we also need to be thinking about how neurocognitive functioning and mental health affect one’s ability to manage their disease in terms of taking medications, avoiding pain triggers, coping with pain, communicating about symptoms and advocating for needs,” Dr. Hardy said. “Future work will look to see if we can preserve neurocognitive functioning and support mental health as a way to reduce pain impairment and improve quality of life.”

Children’s National is conducting several studies focused on better understanding the course of neurocognitive functioning and pain in pediatric SCD. Psychologists in the CCBD are also exploring novel interventions to preserve neurocognitive functioning and promote the development of effective strategies for coping with pain in SCD.

Cancer cells

DOD $1.3M award will launch clinical trial to treat sarcoma

Cancer cells

MPNST is a type of cancer called a sarcoma.

The Department of Defense (DOD) awarded Children’s National Hospital $1.3M to launch a unique clinical trial. The trial will evaluate the safety of a novel drug for patients with a rare but aggressive cancer known as malignant peripheral nerve sheath tumors (MPNST).

MPNST is a type of cancer called a sarcoma. While rare in the general population, about half of all MPNST are diagnosed in people with Neurofibromatosis Type 1 (NF1), a condition characterized by changes in skin coloring.

“MPNST is a life-threatening cancer for which there are no adequate medical options,” said AeRang Kim, M.D., Ph.D., director of clinical research of the Division of Oncology at Children’s National. “With the support of this grant, we will conduct a clinical trial to identify effective agents that could be of great benefit to all patients with NF1 who are at risk for sarcoma.”

MPNST are aggressive and frequently metastasize. The tumors that are not able to be removed with surgery rapidly progress and become lethal. In people with NF1, MPNST often develops within benign tumors, especially atypical benign tumors.

The hold-up in the field

Scientists have been looking at the cell signaling process within both pre-cancerous tumors and cancerous MPNST. Previous research has shown that the MEK and MDM2 signaling pathway influence the development and growth of these tumors. By blocking this interplay, the Zhu Laboratory at Children’s National has demonstrated that tumors can get smaller when treated with drugs that inhibit MEK and MDM2 in pre-clinical models.

What’s unique

The trial is uniquely designed to evaluate target inhibition of novel drugs by looking at signals that may help in determining tumor response. This work will provide people with NF1 and MPNST potentially helpful treatments and increase the knowledge for all people with NF1 and those at risk of MPNST. The drugs will be available to all patients who enroll to the study.

First-of-its-kind holistic program for managing pain in sickle cell disease

The new sickle cell clinic prioritizes looking at the whole person and considering multiple factors that promote health.

The sickle cell team at Children’s National Hospital received a grant from the Founders Auxiliary Board to launch a first-of-its-kind, personalized holistic transformative program for the management of pain in sickle cell disease (SCD). The clinic uses an inter-disciplinary approach of hematology, psychology, psychiatry, anesthesiology/pain medicine, acupuncture, mindfulness, relaxation and aromatherapy services.

Focusing on the “whole person health,” this clinic prioritizes looking at the whole person — not as individual organs or body systems — and considering multiple factors that promote health. Strategies taught in the clinic allow patients to manage their pain effectively by improving self-efficacy, coping mechanisms, and encouraging use of non-opioid and non-pharmacological modalities for pain management. Below, Deepika Darbari, M.D., hematologist and lead of the clinic, and Andrew Campbell, M.D., director of the Comprehensive Sickle Cell Disease Program, tell us more about this unique clinic.

Q: What’s been the hold-up in the field to implement a clinic like this?

A: There are many barriers at different levels in establishing a clinic like this. Most commonly it is the lack of provider expertise, which may not be available at many institutions. Furthermore, services may be available but may not be covered by health insurance. Sometimes, access to these services may be difficult because of the limited locations where they may be offered and not in conjunction with a patient’s hematology care – like in our clinic – which adds to the burden for patients and their families.

Q: How does this work move the field forward in the space of SCD?

A: This clinic is a unique concept where patients and their families actively contribute to and are at the center of the management plan. The goal of this clinic is to provide holistic care to our patients and families and positively impact all aspects of their wellbeing.

Instead of treating a specific disease, “whole person health” focuses on restoring health, promoting resilience and preventing diseases across the patient’s lifespan.

This clinic will continue to provide traditional treatment options for management of SCD along with non-opioids and nonpharmacologic therapies for management of pain, which is the most common complication of SCD.

We are not aware of any such multidisciplinary clinic for SCD like ours at Children’s National. Our team has been invited to national and international scientific conferences to share our experience and educate other programs about how to establish and sustain a clinic like ours.

Q: How will this clinic benefit patients?

A: In SCD, the symptom of pain can start as early as in the first 6 months of life and continue to occur through the lifespan of a patient, often turning into a chronic pain condition. This chronic pain is very refractory to traditional treatments including strong medications like opioids, which may not provide relief while contributing to many side effects. Our goal for patients attending this clinic is to improve their pain experience without increasing side effects.

We hope that the approach offered in this clinic will allow us to decrease the incidence and burden of chronic pain in individuals living with SCD. We would like to offer these treatment strategies early in life, which may help reduce the burden of chronic pain in our patients. We also hope that patients who have developed chronic pain can utilize these strategies to manage their pain, enhance function, reduce opioid use and improve health-related quality of life.

Q: What are you most excited about?

A: We are very excited to build upon our previous work in this space. Our pilot program was started by members of our multidisciplinary team who volunteered their time and effort for this important work.

While providing care to our families and patients, we are also looking forward to collecting robust data that can demonstrate the impact of such an approach in reducing burden of pain in SCD. This data will be helpful in supporting future research and expansion of this approach to benefit all individuals living with SCD.

 

boy using spirometer

Hydroxyurea initiation improves spirometry results in children with sickle cell anemia

boy using spirometer

Hydroxyurea therapy may help preserve lung function over time in children with sickle cell anemia.

Children’s National researchers participated in a recent study suggesting that the use of hydroxyurea (HU) therapy in children with sickle cell anemia (SCA) may help preserve lung function over time.

Sickle cell disease is associated with various pulmonary complications, including reactive airways, acute chest syndrome (ACS), pulmonary fibrosis and pulmonary arterial hypertension, which can lead to increased morbidity and mortality. Lung function tends to decline over time in individuals with SCA, and a more irreversible restrictive pathology develops with age and increasing respiratory complications.

Hydroxyurea is a disease-modifying therapy that has been shown to lower the rates of several complications of SCD, such as ACS and painful vaso-occlusive crises. It also might help lessen the severity of airway hyperreactivity in children.

This study provides evidence that hydroxyurea therapy may have a positive impact on pulmonary function in children with SCA, which could be of interest to doctors treating this patient population. By slowing the decline in lung function, hydroxyurea therapy may help reduce the risk of pulmonary complications and improve the overall health outcomes of children with SCA.

You can read the full study, Spirometric Changes After Initiation of Hydroxyurea in Children With Sickle Cell Anemia, in the Journal of Pediatric Hematology/Oncology.

Authors on the study from Children’s National Hospital include Dinesh Pillai, M.D., Deepika Darbari, M.D., and Anastassios Koumbourlis, M.D., M.P.H.

MRI Room

Using high-intensity focused ultrasound to treat solid tumors

“I think high-intensity focused ultrasound is a really exciting technology that will allow for a different paradigm of how we think about treating solid tumors, both in a local and in a systemic way,” says AeRang Kim, M.D., oncologist at Children’s National Hospital. Dr. Kim explains high-intensity focused ultrasound (HIFU) and how she and her team have used this technology to treat pediatric solid tumors.

HIFU is energy that can be focused on any region of the body. It allows doctors to provide different types of energy in varying amounts, and it’s typically coupled with magnetic resonance imaging, which allows for precise, focused energy to specific areas with accuracy and temperature guidance.

Children’s National was one of the first pediatric centers to open a clinical trial for the treatment of pediatric solid tumors. Since then, we’ve opened several other clinical trials and combined them with targeted chemotherapy for the ablation of benign tumors and malignant solid tumors. We are one of the few institutions that have this study open and we are leading the clinical trials and coordinating them with other institutions across the country.