Cancer

Karun-Sharma-and-kids-MR-HIFU

FDA approves MR-HIFU system to treat osteoid osteoma

Karun-Sharma-and-kids-MR-HIFU

“This FDA approval encourages and further motivates our focused ultrasound program to continue to develop and expand clinical applications of MR-HIFU in the pediatric population,”  said Karun Sharma, M.D., Ph.D.

After garnering successful clinical trial results at Children’s National Hospital, the United States Food and Drug Administration (FDA) recently announced the approval of Profound Medical’s Sonalleve MR-guided High Intensity Focused Ultrasound (MR-HIFU) system for the treatment of osteoid osteoma (OO) in the extremities. OO is a benign, but painful bone tumor that occurs most commonly in children and young adults. This marks the first focused ultrasound regulatory approval that will directly impact pediatric patients and it is the sixth indication to earn approval in the United States.

Nine patients were treated in a pilot trial designed to evaluate the safety and feasibility of MR-HIFU ablation treatment in patients with painful OO. The procedure was performed without any technical difficulties or serious adverse events in all nine patients, and resulted in complete pain relief with no further pain medication usage in eight out of nine patients.

“This FDA approval encourages and further motivates our focused ultrasound program to continue to develop and expand clinical applications of MR-HIFU in the pediatric population,” said Karun Sharma, M.D., Ph.D., director of Interventional Radiology and associate director of clinical translation at the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI) at Children’s National. “This completely non-invasive and radiation-free aspects of this therapy are especially relevant for growing children.”

Researchers at Children’s National have moved beyond OO are also evaluating MR-HIFU treatment for patients with relapsed and refractory bone and soft tissue tumors. “This is especially important as these patients don’t have any other good treatment options,” said Dr. Sharma. “For these tumors, we are using not only thermal ablation, but also other modes and biomechanisms of focused ultrasound such as mild hyperthermia to facilitate targeted, enhanced drug delivery and histotripsy (i.e., mechanical tissue fractionation) to enhance cancer immunotherapy. We also hope to move into MR-HIFU brain application in pediatrics.”

At Children’s National, a multidisciplinary team of physicians and scientists use MR-HIFU to focus an ultrasound beam into lesions to heat and destroy the tissue in that region, with no incisions at all. In 2015, Children’s National doctors became the first in the U.S. to use MR-HIFU to treat pediatric osteoid osteoma. The trial, led by Dr. Sharma, demonstrated early success in establishing the safety and feasibility of noninvasive MR-HIFU in children as an alternative to the current, more invasive approaches to treat these tumors. Since then, the Children’s National team has built an active clinical trials program and become a leader in translation of focused ultrasound for the treatment of relapsed pediatric solid tumors.

Dr. Roger Packer presents at a meeting

Roger Packer, M.D., presents keynote address at First International Pakistan Neuro-Oncology Symposium

Dr. Roger Packer presents at a meeting

During his presentation, he addressed attendees on the topic of the “Modern Management of Medulloblastoma,” discussing results of recently completed clinical trials and the implications of new molecular insights into medulloblastoma, the most common childhood malignant brain tumor.

In late November 2020,  Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, presented as the inaugural keynote speaker for the First International Pakistan Neuro-Oncology Symposium in Karachi, Pakistan.

During his virtual presentation, he addressed attendees on the topic of the “Modern Management of Medulloblastoma,” discussing results of recently completed clinical trials and the implications of new molecular insights into medulloblastoma, the most common childhood malignant brain tumor.

The symposium attracted participants from 57 countries across the globe. There were over 1,000 attendees and as a result of the success of this symposium, there is now a monthly pediatric neuro-oncology lecture series. Dr. Packer agreed to lecture again to the group in mid-January 2021 on “Pediatric Neural Tumors Associated with NF1” as part of an international lecture series hosted by the Aga Khan University in Pakistan.

This is one of multiple national and international activities led by the Brain Tumor Institute at Children’s National Hospital. Directed by Dr. Packer with Eugene Hwang, M.D. as his co-director, and who is associate division chief of oncology at Children’s National Hospital, the multidisciplinary institute holds a monthly tumor board for colleagues at Dmitry Rogachev National Research Center and the Burdenko Neurosurgery Institute in Moscow, Russia, and a monthly brain tumor board coordinated by the Pediatric Oncology Program for colleagues across São Paulo, Brazil.

This also leads to a bi-monthly regional tumor board, which is attended by staff of the National Cancer Institute, the University of Virginia, Inova Children’s Hospital, the University of Maryland Children’s Hospital, Children’s Hospital of Richmond at VCU, Children’s Hospital of The King’s Daughters Health System, Yale University, Geisinger Medical Center, Georgetown University and Carilion Clinic.

conceptual image of bladder cancer

Sensitivity to physical versus chemical factors in CAP

conceptual image of bladder cancer

To date, reactive oxygen species and reactive nitrogen species have been regarded as the key factors causing the observable cellular death of cold atmospheric plasma (CAP)-treated cancer cells. The chemical basis of the conventional CAP treatment highlights apoptosis as the main CAP-triggered cell death mechanism.

However, in a recent study published in the Journal of Physics, Michael Hsieh, M.D., Ph.D., director of Transitional Urology at Children’s National Hospital, and other experts demonstrated a strong anti-melanoma effect based on physically-based CAP treatment. The study, which also tested bladder cancer, compared the anti-cancer effect of chemically-based versus physically-based CAP treatment on four typical cancer cell lines in vitro.

Research & Innovation Campus

Virginia Tech, Children’s National Hospital award $100,000 to fund collaborative cancer research pilot projects

Research & Innovation Campus

This pilot research program represents a growing academic research partnership between Children’s National and Virginia Tech. Last year, the two institutions announced that Virginia Tech will establish a biomedical research facility on the Children’s National Research & Innovation Campus.

Children’s National Hospital and Virginia Tech have awarded two $50,000 one-year pilot grants to multi-institutional teams of scientists for pediatric brain cancer research.

The inter-institutional program, which launched in December, promotes cross-disciplinary collaborations among researchers at both institutions. At Virginia Tech, the program is part of the Virginia Tech Cancer Research Alliance. Financial support for the program was provided by the Offices of the Physician-in-Chief and Chief Academic Officer at Children’s National, and by Virginia Tech’s Office of the Vice President for Health Sciences and Technology.

“We were delighted to see so many innovative and competitive research proposals for our first round of pilot grants in the area of brain cancer. By forging new research collaborations with our partners at Children’s National, we hope to make major strides in addressing one of the most common and devastating groups of cancers in children,” said Michael Friedlander, Virginia Tech’s vice president for health sciences and technology, and the executive director of the Fralin Biomedical Research Institute at VTC. “The pilot funding will bootstrap several programs to be able to acquire ongoing sustainable funding by providing the opportunity to test novel high impact ideas for new strategies for treating these disorders. There are simply too few good options for children in this space now and this partnership can change that for the better.”

The collaborative research initiative began through an agreement between the Fralin Biomedical Research Institute and the Children’s National Research Institute. The collaborative teams formed through a series of interactive discussions among Virginia Tech’s Cancer Research Alliance faculty members from the university’s Blacksburg and Roanoke campuses, and Children’s National’s neuro-oncology researchers.

“I am extremely excited by this collaboration between VT and CNH that is focused on pediatric brain tumors which is such an area of unmet need,” said Catherine Bollard, M.D., M.B.Ch.B.,, director of Children’s National’s Center for Cancer and Immunology Research. “I am confident that the funded proposals will soon advance our understanding of pediatric brain tumors and, more importantly, facilitate more joint efforts between two world-class institutions which is especially timely with the development of the Children’s National Research & Innovation Campus.”

Yanxin Pei, Ph.D., an assistant professor in the Center for Cancer Immunology Research at Children’s National, and Liwu Li, Ph.D., a professor of biological sciences in Virginia Tech’s College of Science, were awarded one of the pilot research grants to study how white blood cells called neutrophils are involved in metastatic MYC-driven medulloblastoma, an aggressive type of brain tumor in children that often resists conventional radiation and chemotherapies.

Yuan Zhu, Ph.D., the Gilbert Family Professor of Neurofibromatosis Research at Children’s National, and Susan Campbell, Ph.D., an assistant professor of animal and poultry sciences in Virginia Tech’s College of Agriculture and Life Sciences, were awarded funds to study glioma-induced seizures in mice with a genetic mutation that inhibits the production of P53, a key protein involved in suppressing cancer cell growth and division.

The successful applicants will receive funding starting this month and are expected to deliver preliminary data to support an extramural research application by 2024.

This pilot research program represents a growing academic research partnership between Children’s National and Virginia Tech. Last year, the two institutions announced that Virginia Tech will establish a biomedical research facility on the Children’s National Research & Innovation Campus. It will be the first research and innovation campus in the nation focused on pediatrics when it opens later this year and will house newly recruited teams of pediatric brain cancer researchers.

Liwu Li, Yanxin Pei, Susan Campbell, and Yuan Zhu

Liwu Li, Ph.D., Yanxin Pei, Ph.D., Susan Campbell, Ph.D., and Yuan Zhu, Ph.D., were awarded funding through the new pilot research program.

Lee Beers

Lee Beers, M.D., F.A.A.P, begins term as AAP president

Lee Beers

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Lee Savio Beers, M.D., F.A.A.P., medical director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital, has begun her term as president of the American Academy of Pediatrics (AAP). The AAP is an organization of 67,000 pediatricians committed to the optimal physical, mental and social health and well-being for all children – from infancy to adulthood.

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Dr. Beers has pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

  • Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns.
  • Continuing to support pediatricians during the COVID-19 pandemic with a focus on education, pediatric practice support, vaccine delivery systems and physician wellness.
  • Implementation of the AAP’s Equity Agenda and Year 1 Equity Workplan.

Dr. Beers is looking forward to continuing her work bringing together the diverse voices of pediatricians, children and families as well as other organizations to support improving the health of all children.

“Dr. Beers has devoted her career to helping children,” says Kurt Newman, M.D., president and chief executive officer of Children’s National. “She has developed a national advocacy platform for children and will be of tremendous service to children within AAP national leadership.”

Read more about Dr. Beer’s career and appointment as president of the AAP.

Roger Packer with patient

A lifetime of achievements: Roger Packer, M.D.

Roger Packer with patient

Over the years, Dr. Packer and his team in Washington, D.C., have made meaningful contributions to children all around the world diagnosed with childhood brain tumors, including medulloblastoma and gliomas.

Earlier in December, Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, received the 2020 Lifetime Achievement Award from the International Symposium on Pediatric Neuro-Oncology at the meeting organized in Karuizawa, Japan. The prestigious recognition is a testament to the years of commitment and dedication Dr. Packer has devoted to the care of children with brain tumors and as such, have placed him as a top leader.

This award is a recognition of how the field has grown since the first International Symposium on Pediatric Neuro-Oncology Dr. Packer organized in Seattle in 1989. “It grew from a small gathering of investigators to now a multidisciplinary group of over 2,000 investigators,” Dr. Packer says.

Over the years, Dr. Packer and his team in Washington, D.C., have made meaningful contributions to children all around the world diagnosed with childhood brain tumors, including medulloblastoma and gliomas. These findings have contributed to an increase of the survival rate from 50% to over 80% for children with medulloblastoma. In addition, his contributions have led to newer molecular targeted therapies and improved the quality of life of children who are long-term survivors.

“The field, especially in the last decade, rapidly transitioned to a more biologically informed field,” Dr. Packer explains. “We are now utilizing new, exciting discoveries in biology and genetics to inform new approaches to treatment. This kind of transition gives us great hope for the future.”

In his early career, Dr. Packer worked with two neuro-oncology patients who died and would impact his decision to further study this field. At that time, there was minimal understanding of the nature of neuro-oncology diseases or how to best treat them. As a neurologist, he was frustrated by the lack of understanding and as a pediatrician, he was frustrated at the lack of ability to do success management.

“I saw this as a gap in my personal knowledge and found that the field was struggling to come up with new answers and new approaches,” he says. “But at the same time other, advances were being made in child cancer care, such as with leukemia. However, there was no wide focus on pediatric brain tumors.”

Combining his knowledge of neurology with his curiosity and relying on other leaders that surrounded him in the same field, Dr. Packer worked on driving this new work forward. Today, he is still heavily involved in the development of treatment protocols that are increasingly transitional for a variety of brain tumors, including low-grade and high-grade gliomas.

“With the help of our great colleagues at Children’s National, we continue to try to develop new means to treat these tumors, including immunological approaches and the incorporation in the use of novel means, such as low-intensity and high-intensity focused ultrasound,” he says. “We also have an excellent multidisciplinary team at Children’s National that has grown over the last decade some of whom are acknowledged national leaders in the fields of brain tumors, clinical research and clinical care. We also have a robust program focusing on the neurocognitive outcome of children and ways to intervene to ameliorate intellectual compromise and improve quality of life.”

DNA Molecule

Epigenetics and pediatric brain tumors

DNA Molecule

Over the last two decades the critical role of epigenetics in cancer biology has evolved significantly. In parallel, our understanding of the biology of many pediatric brain tumors and the central role of alterations in their epigenetic regulation has become an important area of discovery.

In an editorial in a special issue of the Journal of Neuro-OncologyRoger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, looks at understanding the role of epigenetics and how they will further characterize pediatric brain tumors, open new therapeutic avenues for treatment and lead to true breakthroughs and cures for children.

person with brain tumor

Update on pediatric brain tumors

person with brain tumor

Over the last five years, there has been tremendous growth in the field of pediatric neuro-oncology with increasing understanding of the genetic and epigenetic heterogeneity of central nervous system (CNS) tumors. Attempts are underway to translate these insights into tumor-specific treatments. A recent review article in Current Neurology and Neuroscience Reports by Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, provided an update on the current landscape of pediatric brain tumors and the impact of novel molecular insights on classification, diagnostics and therapeutics.

blood cells with sickle cell anemia

Advances in therapy for sickle cell disease and hemophilia

blood cells with sickle cell anemia

Despite having a network of providers and a national database, access to care and treatment burden continue to be issues that affect quality of life in the hemophilia population.

Hemophilia and sickle cell are disorders that are associated with comorbidities and significant treatment burden, discussed Christine Guelcher, PPCNP-BC, lead advanced practice provider for the Center for Cancer and Blood Disorders at Children’s National Hospital, during the virtual 62nd ASH Annual Meeting and Exposition.

During the satellite symposia, Guelcher explained a network of hemophilia treatment centers (HTCs) was developed in the 1970s. The model of multi-disciplinary care in the HTC network has demonstrated improved outcomes. Despite having a network of providers and a national database, access to care and treatment burden continue to be issues that affect quality of life in the hemophilia population.

“While similar programs were developed in sickle cell with similar improvements in care, the funding was not sustained,” Guelcher said. However, efforts are underway to develop multi-disciplinary care and data infrastructure in the sickle cell community.

“The lack of specialized providers, particularly adult hematologists, continues to be an issue for both non-malignant hematologic disorders,” she added.

Advances in care

While hemophilia is rare, it is an expensive disease. Controlling bleeding with medications is expensive and associated with significant treatment burden. Failure to prevent bleeding due to lack of access or adherence can result in debilitating bleeding that impacts on productivity and quality of life. Additionally, clinical trials with gene therapy are ongoing, though questions remain about sustained levels and durability.

“Recent development of drugs that can reduce the frequency of intravenous infusions (extended half-life factor replacement products or subcutaneous novel non-factor prophylaxis) have improved the treatment burden,” Guelcher said. “But access to care continues to be an issue for up to 30% of the patients with bleeding disorders in the U.S.” Sickle cell disease affects mostly Black/African American and Hispanic patients, many of whom already experience health care disparities. While newborn screening, antibiotic prophylaxis and immunizations have decreased life-threatening infections, vaso-occlusive (pain) crisis continues to be a debilitating complication. Furthermore, stroke, pulmonary, cardiac and renal disease are significant comorbidities.

While advances in therapies for sickle cell have provided new treatment options to decrease the frequency of vaso-occlusive crisis, the pathophysiology that results in all of the sequalae is not fully understood. While Bone marrow transplant is potential treatment of the underlying sickle cell disease process, only 20% of patients have a matched sibling donor. Currently, clinical trials are investigating the safety and efficacy of gene therapy. Despite all of these advances, the life expectancy of somebody with sickle cell is 30 years shorter than the general U.S. population.

Access to care

The multi-disciplinary panel presentation at ASH gave participants an opportunity to hear about the challenges facing these patients and families. The overview of new and emerging treatment options gave providers an understanding of treatment options.

“Hopefully, presentations like this will inspire providers to consider a career in non-malignant hematology (particularly adult providers),” Guelcher added.

As one of the nation’s hemophilia and thrombosis treatment centers, Children’s National Hospital provides comprehensive, multi-disciplinary care. Patients can participate in two national registries in order to collect aggregate data that are used to identify trends that impact bleeding disorder patients. Our sickle cell program also offers multi-disciplinary clinics for infants, integrative care for chronic pain and transition, addressing some of the unmet needs that continue to be an issue nationally.

“We also participate in industry sponsored clinical trials to ensure that new therapies, including gene therapy, are safe and effective,” Guelcher explained. “This gives our patients access to state-of-the-art care. Numerous clinical trials to ensure that recently licensed products and gene therapy are safe for use in a pediatric patient with hemophilia and sickle cell are ongoing.”

Roger Packer

Roger Packer, M.D., receives Lifetime Achievement Award

Roger Packer

“I am very honored and humbled to receive this recognition from the International Symposium on Pediatric Neuro-Oncology,” says Roger Packer, M.D. “I am proud of the contributions my team and I have made in this field and we look forward to continue to lead research focused on the advancement of the crucial areas neuro-oncology.”

Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, will receive the 2020 Lifetime Achievement Award from the International Symposium on Pediatric Neuro-Oncology. Dr. Packer was selected as a recipient for the prestigious award for his substantial contributions to pediatric oncology and scientific achievements.

“I am very honored and humbled to receive this recognition from the International Symposium on Pediatric Neuro-Oncology,” says Dr. Packer. “I am proud of the contributions my team and I have made in this field and we look forward to continue to lead research focused on the advancement of the crucial areas neuro-oncology.”

Dr. Packer is also a Gilbert Distinguished Professor of Neurofibromatosis and is Director of both the Gilbert Neurofibromatosis Institute and the Brain Tumor Institute of Children’s National Hospital. Most of the current studies Dr. Packer coordinates are studies evaluating innovative agents aimed at the molecular underpinnings of neurologic disease. He has published over 400 original articles and 350 reviews and chapters.

The award will be presented at ISPNO 2020, the 19th International Symposium on Pediatric Neuro-Oncology, December 13-16, 2020, in Karuizawa, Japan.

Children’s National Hospital is incredibly proud of the work Dr. Packer has done in the neuro-oncology community.

graphic abstract for brain tumor paper

First large-scale proteogenomic analysis offers insights into pediatric brain tumor biology

graphic abstract for brain tumor paper

In the first large-scale, multicenter study of its kind, researchers conducted comprehensive analysis yielding a more complete understanding of pediatric brain tumors (PBT), which are the leading cause of cancer-related deaths in children. Researchers from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Children’s Brian Tumor Network (CBTN) generated and analyzed proteomic data, which identifies common biological characteristics among different tumor types. The consortia consist of collaborators from the Icahn School of Medicine at Mount Sinai, National Cancer Institute, Fred Hutchinson Cancer Research Center, Children’s National Hospital and Children’s Hospital of Philadelphia. The study, published in Cell on November 25, 2020, provides a clearer understanding of the molecular basis of pediatric brain tumors and proposes new therapeutic avenues.

The molecular characterization of brain tumors has largely hinged upon the presence of unique alterations in the tumor genome ignoring the many layers of regulation that exist between DNA and the functional biology of the tumor cell that is actuated by proteins. The integration of proteomic data identifies common biological themes that span histologic boundaries, suggesting that treatments used for one histologic type may be applied effectively to other tumors sharing similar proteomic features.

Brian Rood, M.D., medical director of the Brain Tumor Institute and associate professor of pediatrics in the Center for Cancer and Blood Disorders at Children’s National Hospital, participated in this study and explains the importance of what the team discovered.

Q: Why was it important that researchers came together to do this work?

A: Comprehensive characterization of the fundamental biology of pediatric brain tumors, including the proteogenomic analysis done in this study, is essential to better understand and treat pediatric brain tumors.

Our study is based on the recognition that proteomics and phosphoproteomics needs to be integrated with other omics data to gain an improved systems biology view of the molecular features of brain tumors. In addition, characterizing biological themes that cross histologic boundaries and cells of origin can suggest extending treatments shown to be effective in one type of tumor to other histologically disparate tumors sharing the same proteomic features.

Proteomic data further reveal the functional impacts of somatic mutations and copy number variations (CNVs) not evident in transcriptomic data alone. Further, kinase-substrate network analyses identify activated biological mechanisms of tumor biology.

This work was only possible because of a unique collaboration between the CPTAC program of the NCI and the CBTN, of which Children’s National is a member.

Q: How will this work advance understanding and treatment of pediatric brain tumors?

A: Pediatric brain tumors have not benefitted from molecularly targeted drugs as much as other tumor types largely because they harbor relatively few gene mutations. Therefore, identifying key pathways to target in these patients’ tumors has been a challenge. The integration of proteomic and phosphoproteomic data with genomic data allows for the construction of a more comprehensive model of brain tumor biology and nominates specific key pathways to be targeted.

Q: What did you find that excites you?

A: Proteomic data revealed a number of findings that were not present in the genomic data. We found evidence to support a molecularly targeted approach to treating craniopharyngioma, a tumor that has previously been unresponsive to chemotherapy. We also found a prognostic marker for high grade gliomas that do not have a mutation in the H3 histone. We were able to identify specific kinases that may dictate the aggressive nature of certain ependymoma tumors. Importantly, we demonstrated the potential of proteomic studies to uncover unique tumor biology, paving the way for more extensive investigations using this approach.

You can find the full study published in Cell. Learn more about the Brain Tumor Institute at Children’s National.


Dr. Rood recently joined a live panel discussion with researchers from the Children’s Brain Tumor Network and the Clinical Proteomic Tumor Analysis Consortium to explore the impact of their landmark study.

tumor cells

Promising new pediatric oncologic applications for focused ultrasound

tumor cells

Earlier this month, AeRang Kim, M.D., Ph.D., oncologist at Children’s National Hospital, spoke at the Focused Ultrasound Foundation’s 7th International Symposium on Focused Ultrasound about the latest developments in focused ultrasound applications for pediatric oncology.

Dr. Kim and a team of researchers at Children’s National belong to the IGNITE (image guided non-invasive therapeutic energy) team, a multidisciplinary group working to develop and transform focused ultrasound applications that will minimize treatment side effects and increase efficacy in pediatric cancer care.

In 2015, the IGNITE team conducted its first trial with a study of MR-guided high-intensity focused ultrasound (MR-HIFU) for treating painful osteoid osteomas (a benign bone tumor) in children. This was followed by a trial of MR-HIFU ablation for pediatric solid tumors.

“MR-HIFU has a potential role in local treatment of tumors, both benign and malignant,” Dr. Kim said. “What I’m most excited about is that MR-HIFU has the flexibility to be combined with other treatments such as heat sensitive targeted therapy and immune therapy. I believe this combination approach will have the highest impact in terms of safety and efficacy in pediatric cancer care.”

Aerang Kim

“MR-HIFU has a potential role in local treatment of tumors, both benign and malignant,” says AeRang Kim, M.D., Ph.D. “What I’m most excited about is that MR-HIFU has the flexibility to be combined with other treatments such as heat sensitive targeted therapy and immune therapy.”

Focused ultrasound is an emergent, non-invasive therapeutic technology that uses ultrasonic energy to target tissue deep in the body without incisions or radiation, thus resulting in minimal discomfort and few complications. This also allows for rapid patient recovery. The applications are wide-ranging: from thermal ablation of tumors and other lesions to blood-brain barrier opening, to increasing tumor vasculature for improved drug delivery, to augmenting immune response, among many others.

The team is now working on combinations of focused ultrasound with other therapies, such as chemotherapy. On the third clinical trial open for accrual at Children’s National, they combine MR-HIFU with lysothermosensitive liposomal doxorubicin, a heat-activated form of the cancer drug doxorubicin, to treat pediatric solid tumors. Although results are still preliminary, the hope is that the technology will mitigate some of the acute and late effects of current multimodal therapy in children. “We want to provide more efficacy and precision with these therapies,” said Dr. Kim.

In reflecting on the potential of this new approach, Dr. Kim believes the findings can help change the way experts think about cancer treatment.  The team is studying pre-clinical models of pediatric cancer to evaluate the different modalities of MR-HIFU with immune checkpoint inhibitors. Understanding that there are limitations of MR-HIFU ablation alone, Dr. Kim believes the future for most pediatric cancer applications will be combining approaches using the various bioeffects of focused ultrasound.

“We hope that if promising effects in multiple models utilizing this combination, we can translate these findings into the clinical setting,” she said, noting that the clinical trials led by her team are among the first in the U.S. of HIFU for children. “Children’s National is one of the first pediatrics centers to lead a HIFU program and the Focus Ultrasound Foundation’s first Center of Excellence focused exclusively in pediatrics.  We hope to continue to expand our findings and improve pediatric cancer care that’s more precise, less toxic, less invasive and pain free.”

Research & Innovation Campus

Boeing gives $5 million to support Research & Innovation Campus

Research & Innovation Campus

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus.

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus. The campus, now under construction, is being developed on nearly 12 acres of the former Walter Reed Army Medical Center. Children’s National will name the main auditorium in recognition of Boeing’s generosity.

“We are deeply grateful to Boeing for their support and commitment to improving the health and well-being of children in our community and around the globe,” said Kurt Newman, M.D., president and CEO of Children’s National “The Boeing Auditorium will help the Children’s National Research & Innovation campus become the destination for discussion about how to best address the next big healthcare challenges facing children and families.”

The one-of-a-kind pediatric hub will bring together public and private partners for unprecedented collaborations. It will accelerate the translation of breakthroughs into new treatments and technologies to benefit kids everywhere.

“Children’s National Hospital’s enduring mission of positively impacting the lives of our youngest community members is especially important today,” said Boeing President and CEO David Calhoun. “We’re honored to join other national and community partners to advance this work through the establishment of their Research & Innovation Campus.”

Children’s National Research & Innovation Campus partners currently include Johnson & Johnson Innovation – JLABS, Virginia Tech, the National Institutes of Health (NIH), Food & Drug Administration (FDA), U.S. Biomedical Advanced Research and Development Authority (BARDA), Cerner, Amazon Web Services, Microsoft, National Organization of Rare Diseases (NORD) and local government.

The 3,200 square-foot Boeing Auditorium will be the focal point of the state-of-the-art conference center on campus. Nationally renowned experts will convene with scientists, medical leaders and diplomats from around the world to foster collaborations that spur progress and disseminate findings.

Boeing’s $5 million commitment deepens its longstanding partnership with Children’s National. The company has donated nearly $2 million to support pediatric care and research at Children’s National through Chance for Life and the hospital’s annual Children’s Ball. During the coronavirus pandemic, Boeing fabricated and donated 2,000 face shields to help keep patients and frontline care providers at Children’s National safe.

Catherine Bollard

Catherine Bollard, M.D., M.B.Ch.B., named next editor-in-chief of Blood Advances

Catherine Bollard

“As editor-in-chief, I will aim to capture new developments in the hematology field, including immunology, immunotherapy, cell therapy, gene and cell therapy and transplant,” said Dr. Bollard.

The American Society of Hematology (ASH) has selected Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at the Children’s National Research Institute as the next editor-in-chief of its journal Blood Advances.

Blood Advances is a peer-reviewed online open access journal published by ASH that covers the latest developments in basic, translational and clinical hematology. Dr. Bollard’s term as editor-in-chief will begin in September 2021. She was selected by the ASH Executive Committee after a competitive international search.

Blood Advances has a broad presence, a large and growing number of manuscript submissions, and an engaged readership,” said Dr. Bollard. “I am so looking forward to continuing to build and strengthen the journal as its editor-in-chief.”

Since its launch in 2016, Blood Advances has taken advantage of its digital, open-access publication model to emphasize multimedia and a rapid, continuous publication format. Under the leadership of founding editor-in-chief Robert Negrin, M.D., of Stanford University, the peer-reviewed journal has pioneered new means of interactive, collaborative discussion and achieved an impact factor of 4.910.

“As editor-in-chief, I will aim to capture new developments in the hematology field, including immunology, immunotherapy, cell therapy, gene and cell therapy and transplant,” said Dr. Bollard. Her vision for the future of Blood Advances also includes further expansion of the journal’s global reach as well as continued efforts to recruit an editorial team representing geographic, ethnic and gender diversity.

“We have tremendous opportunities for growth, and I think in order to grow we must consider what readers want, how we can provide quality service for authors and reviewers, and how we can establish our own identity as a journal,” she said.

Dr. Bollard is a hematologist whose research interests include developing cell and gene therapies for patients with cancer and underlying immune deficiencies. Recognized as a national and international leader in the bone marrow transplant, immunology and immunotherapy space, Dr. Bollard has an expansive understanding of cancer, immune deficiencies and viral infections in pediatric and adult patients.

In her role as director of the Center for Cancer and Immunology Research at Children’s National Hospital, she works to establish clinical and research programs focused on developing and bringing novel cell therapies from bench to bedside.

Blood Advances is an important hub for hypothesis-generating papers, pilot studies and case reports, commentaries and other educational materials of interest to hematologists everywhere,” said ASH President Stephanie Lee, M.D., of Fred Hutchinson Cancer Research Center. “I am confident that Dr. Bollard will continue leveraging the journal’s unique digital platform to maintain its tradition of excellence as she executes her vision as editor-in-chief. I look forward to seeing how the journal evolves under her leadership.”

coronavirus

T-cells show promise to protect vulnerable patients from COVID-19 infection

coronavirus

Children’s National Hospital immunotherapy experts have found that T-cells taken from the blood of people who recovered from a COVID-19 infection can be successfully multiplied in the lab and maintain the ability to effectively target proteins that are key to the virus’s function.

Children’s National Hospital immunotherapy experts have found that T-cells taken from the blood of people who recovered from a COVID-19 infection can be successfully multiplied in the lab and maintain the ability to effectively target proteins that are key to the virus’s function. Their findings were published Oct. 26, 2020, in Blood.

“We found that many people who recover from COVID-19 have T-cells that recognize and target viral proteins of SARS-CoV-2, giving them immunity from the virus because those T-cells are primed to fight it,” says Michael Keller, M.D., a pediatric immunology specialist at Children’s National Hospital, who led the study. “This suggests that adoptive immunotherapy using convalescent T-cells to target these regions of the virus may be an effective way to protect vulnerable people, especially those with compromised immune systems due to cancer therapy or transplantation.”

Based on evidence from previous phase 1 clinical trials using virus-targeting T-cells “trained” to target viruses such as Epstein-Barr virus, the researchers in the Cellular Therapy Program at Children’s National hypothesized that the expanded group of COVID-19 virus-targeting T-cells could be infused into immunocompromised patients, helping them build an immune response before exposure to the virus and therefore protecting the patient from a serious or life-threatening infection.

“We know that patients who have immune deficiencies as a result of pre-existing conditions or following bone marrow or solid organ transplant are extremely vulnerable to viruses like SARS-CoV-2,” says Catherine Bollard, M.D., M.B.Ch.B., senior author of the study and director of the novel cell therapies program and the Center for Cancer and Immunology Research at Children’s National. “We’ve seen that these patients are unable to easily clear the virus on their own, and that can prevent or delay needed treatments to fight cancer or other diseases. This approach could serve as a viable option to protect or treat them, especially since their underlying conditions may make vaccines for SARS-CoV-2 unsafe or ineffective.”

The T-cells were predominantly grown from the peripheral blood of donors who were seropositive for SARS-CoV-2. The study also identified that SARS-CoV-2 directed T-cells have adapted to predominantly target specific parts of the viral proteins found on the cell membrane, revealing new ways that the immune system responds to COVID-19 infection.

Current vaccine research focuses on specific proteins found mainly on the “spikes” of the coronavirus SARS-CoV-2. The finding that T-cells are successfully targeting a membrane protein instead may add another avenue for vaccine developers to explore when creating new therapeutics to protect against the virus.

“This work provides a powerful example of how both scientific advances and collaborative relationships developed in response to a particular challenge can have broad and unexpected impacts on other areas of human health,” says Brad Jones, Ph.D., an associate professor of immunology in medicine in the Division of Infectious Diseases at Weill Cornell Medicine and co-author on the study, whose lab focuses on HIV cure research. “I began working with Dr. Bollard’s team several years ago out of our shared interest in translating her T-cell therapy approaches to HIV. This put us in a position to quickly team up to help develop the approach for COVID-19.”

The Cellular Therapy Program is now seeking approval from the U.S. Food and Drug Administration for a phase 1 trial that will track safety and effectiveness of using COVID-19-specific T-cells to boost the immune response in patients with compromised immune systems, particularly for patients after bone marrow transplant.

illustration of cancer cells attacking kidneys

Renal cell carcinoma study shows excellent short-term outcomes without adjuvant therapy

illustration of cancer cells attacking kidneys

Researchers found that patients with localized pediatric renal cell carcinoma have excellent short-term outcomes without adjuvant therapy.

Although renal cell carcinoma (RCC) is the second most common kidney cancer diagnosed in children and adolescents, guidance regarding its clinical management has been confined to retrospective case series, which were limited by reporting bias, varied treatment approaches and a lack of central pathology review to confirm the diagnosis.

Research conducted by the Children’s Oncology Group (COG) and led by Jeffrey Dome, M.D., Ph.D., vice president of the Center for Cancer and Blood Disorders at Children’s National Hospital, found that patients with localized pediatric RCC have excellent short-term outcomes without adjuvant therapy with 4-year overall survival estimates of 96% for patients with stage I disease, 100% for patients with stage II disease and 88% for patients with stage III disease.

“The results of this study provide important practical insights into the management of pediatric RCC,” said Dr. Dome. “Oncologists now have validation that a surgery-only approach is appropriate management for the majority of children and adolescents with RCC.”

Jeffrey Dome

“The results of this study provide important practical insights into the management of pediatric RCC,” said Jeffrey Dome, M.D., Ph.D.

The excellent survival in patients with stage III disease held up even in those with tumor involvement of regional lymph nodes, a finding that differs from adult RCC. However, patients with metastatic disease (stage IV), had a 4-year overall survival estimate of only 29%, demonstrating the need to find active treatments for this group. Outcomes varied according to tumor histological subtype. Nearly all recurrences occurred in patients with the translocation histology and renal medullary carcinoma; recurrences were rare in other subtypes.

A follow-up study called AREN1721 is now open in the Children’s Oncology Group and adult cancer cooperative groups that participate in the National Clinical Trials Network. This study involves a comparison of two treatment regimens for metastatic or unresectable “translocation” renal cell carcinoma, the most common subtype of renal cell carcinoma in children, adolescents and young adults. The treatment regimens will include nivolumab, a PD1 immune checkpoint inhibitor, with or without axitinib, a tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR).

cystic kidney disease

NIH $4 million grant funds new core center for childhood cystic kidney disease

cystic kidney disease

The University of Alabama at Birmingham (UAB), in collaboration with Children’s National Hospital has received a five-year, $4 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (NIH) to create a core center for childhood cystic kidney disease (CCKDCC). The UAB-CCKDCC will conduct and facilitate research into the causes of and possible treatments for cystic kidney diseases, particularly those that present in childhood.

The UAB/Children’s National grant is a U54 center grant, an NIH funding mechanism to develop a multidisciplinary attack on a specific disease entity or biomedical problem area. With this grant, UAB joins with investigators at the University of Kansas and the University of Maryland-Baltimore as part of the NIH Polycystic Kidney Disease Research Resource Consortium. The NIH describes the consortium as a framework for effective collaboration to develop and share research resources, core services and expertise to support innovation in research related to polycystic kidney disease.

“Infants with childhood cystic kidney disease may develop kidney failure within a few years after birth and some need dialysis and kidney transplantation before they reach adulthood,” said Lisa Guay-Woodford, M.D., director of the Clinical and Translational Science Institute at Children’s National and co-director of the UAB-CCKDCC. “In many cases, the earlier the onset of symptoms, the more severe the outcome.”

“The intent is to accelerate the science and advance research into new therapies for cystic kidney disease through enhanced sharing of resources and the establishment of a robust research community,” said Bradley K. Yoder, Ph.D., professor and chair of the UAB Department of Cell, Developmental and Integrative Biology and co-director of the UAB-CCKDCC. “Childhood polycystic disease can be a devastating condition for children and their families.”

The UAB-CCKDCC will focus primarily on childhood polycystic kidney disease, a condition that affects about one in 20,000 infants in the United States. The center’s primary goals are:

  • Provide the Polycystic Kidney Disease Research Resource Consortium members with access to phenotypic, genetic and clinical information and biomaterials from CCKD patients
  • Analyze pathways involved in cyst pathogenesis through the generation of verified genetic model systems and biosensor/reporter systems
  • Assess the impact of patient variants on cystic disease proteins through generation and validation of innovative models
  • Provide ready access to biological materials from genetic CCKD models
  • Develop efficient pipelines for in vitro and in vivo preclinical testing of therapeutic compounds

Dr. Guay-Woodford is an internationally recognized pediatric nephrologist with a research program focused on identifying clinical and genetic factors involved in the pathogenesis of inherited renal disorders, most notably autosomal recessive polycystic kidney disease (ARPKD). Her laboratory has identified the disease-causing genes in several experimental models of recessive polycystic kidney disease and her group participated in the identification of the human ARPKD gene as part of an international consortium. In addition, her laboratory was the first to identify a candidate modifier gene for recessive polycystic kidney disease. For her contributions to the field, she was awarded the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease, given by the Polycystic Kidney Disease Foundation and the International Society of Nephrology.

Karun Sharma

Children’s National designated Center of Excellence by Focused Ultrasound Foundation

Karun Sharma

“This designation provides a high level of recognition and legitimacy to the work our Children’s National team has done with MR-HIFU over many years,” says Karun Sharma, M.D., PhD, director of Interventional Radiology and associate director of clinical translation at the Sheikh Zayed Institute for Pediatric Surgical Innovation.

More precise, less invasive and less painful surgery with lower risk of complications and no radiation exposure – these are some of the benefits of treating pediatric tumors with Magnetic Resonance Guided High Intensity Focused Ultrasound (MR-HIFU). And now the Focused Ultrasound Foundation has designated Children’s National Hospital as the first global pediatric Center of Excellence (COE) for using this technology to help patients with specific types of childhood tumors.

“This designation provides a high level of recognition and legitimacy to the work our Children’s National team has done with MR-HIFU over many years,” says Karun Sharma, M.D., PhD, director of Interventional Radiology and associate director of clinical translation at the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI) at Children’s National. “This will allow our focused ultrasound program to expand to other areas of interest and become more cohesive while continuing to uncover additional clinical indications for pediatric patients.”

At Children’s National, radiologists use MR-HIFU to focus an ultrasound beam into lesions, usually tumors of the bone and soft tissues, to heat and destroy the tissue in that region. There are no incisions at all. In 2015, Children’s National doctors became the first in the U.S. to use MR-HIFU to treat pediatric osteoid osteoma, a painful, but benign, bone tumor that commonly occurs in children and young adults. The trial, led by Dr. Sharma, demonstrated early success in establishing the safety and feasibility of noninvasive MR-HIFU in children as an alternative to the current, more invasive approaches to treat these tumors. The team also conducted another clinical trial, led by AeRang Kim, M.D., Ph.D., a pediatric oncologist, to treat relapsed soft tissue tumors such as sarcomas.

Since then, the Children’s National team has built an active clinical trials program and become a leader in translation of focused ultrasound for the treatment of pediatric solid tumors. The center is currently investigating the treatment of malignant solid tumors with focused ultrasound alone and combined with chemotherapy.

“Focused ultrasound offers a number of important benefits over traditional therapies, which are especially paramount for the pediatric population,” said Focused Ultrasound Foundation Chairman Neal F. Kassell, M.D. “The team at Children’s National has an exemplary track record in using this technology to pioneer new treatment options for their patients, and we look forward to collaborating and supporting their future research.”

As a designated COE, Children’s National has the necessary infrastructure to support the ongoing use of this technology, especially for carrying out future pediatric clinical trials. This infrastructure includes an ethics committee familiar with focused ultrasound, a robust clinical trials research support team, a data review committee for ongoing safety monitoring and annual safety reviews, and a scientific review committee for protocol evaluation.

The program also features a multidisciplinary team of clinicians and investigators from SZI, radiology, oncology, surgery and orthopedics. With the new designation and continued expansion, we will expand MR-HIFU to other areas such as neuro-oncology, neurosurgery, and urology. Ongoing and future work will investigate a rational combination of MR-HIFU with local tumor drug delivery, immunotherapy and cellular therapy.

“This recognition sets us apart as a premier pediatric institution, and will allow us to pave the way to make pediatric surgery more precise and less invasive,” says Dr. Sharma.

 

Intermediate magnification micrograph of Ewing sarcoma in lung

Clinical Trial Spotlight: A Phase 1, Dose Escalation Study of Intravenous TK216 in Patients with Relapsed or Refractory Ewing Sarcoma

Intermediate magnification micrograph of Ewing sarcoma in lung

Intermediate magnification micrograph of Ewing sarcoma in lung.

Despite advances in chemotherapy, the outcome for metastatic or relapsed Ewing sarcoma (ES) is dismal. ES harbors a pathognomonic translocation EWS-FLI1, leading to an oncogenic fusion protein that drives its development and for years has been considered an undruggable target. TK216 is a unique, investigational agent that targets EWS-FLI1 by disrupting its binding to RHA, a protein partner needed for the activity of EWS-FLI1, and one of the first in class to do so. In pre-clinical models of ES, there was cell death and inhibition of tumor growth which was potentiated with vincristine.

Study TK216-01 is a Phase 1 study of TK216 in patients with relapsed or refractory Ewing sarcoma currently open at a limited number of sites. The initial Phase 1 data demonstrates this drug has been generally well tolerated with encouraging preliminary data in patients. The study is currently in the expansion cohort using the recommended phase 2 dose of TK216 in combination with vincristine and is open to enrollment at Children’s National.

“There was interesting preliminary data presented at the CTOS meeting last November,” says AeRang Kim, M.D., Ph.D., a pediatric oncologist at Children’s National and the study’s principal investigator. “This really is a first-in-class that targets this specific translocation which makes it an exciting option for this patient group.”

Children’s National Hospital is the only pediatric center in the Washington, D.C., region to offer this trial.

TK216 in Patients with Relapsed or Refractory Ewing Sarcoma

For more information about this trial, contact:
Ann Liew, M.S., CCRP
202-476-6755
aliew@childrensnational.org

Click here to view Open Phase 1 and 2 Cancer Clinical Trials at Children’s National.

The Children’s National Center for Cancer and Blood Disorders is committed to providing the best care for pediatric patients. Our experts play an active role in innovative clinical trials to advance pediatric cancer care. We offer access to novel trials and therapies, some of which are only available here at Children’s National. With research interests covering nearly every aspect of pediatric cancer care, our work is making great advancements in childhood cancer.

Kristina Hardy

Kristina Hardy awarded St. Baldrick’s Foundation research grant for supportive care

Kristina Hardy

Kristina Hardy, Ph.D., pediatric neuropsychologist within the Division of Neuropsychology at Children’s National Hospital, was a recipient of a $60,000 grant for children with acute lymphoblastic leukemia (ALL), a cancer of the blood, from the St. Baldrick’s Foundation, the largest charitable funder of childhood cancer research grants. .

Dr. Hardy along with her co-principal investigator in this project, Dr. Sarah Alexander, an oncologist from the Hospital for Sick Children in Toronto, study neurocognitive difficulties in survivors of pediatric cancer. Through their research, both doctors will examine the potential connections between specific anesthesia medications, their doses, the amount of time they’re given and the chances of patients having learning problems later on in life. This critical research will be important for patients, families and clinical teams in helping to make the best choices for anesthesia use.

“About 20-40% of children who are diagnosed with ALL develop problems with thinking and learning after treatment,” said Dr. Hardy. “This research is exciting because if certain types or amounts of anesthesia are shown to increase risk for cognitive changes in survivors, we may be able to quickly change the way that we use anesthesia to lessen the risk.”

The St. Baldrick’s Foundation is on a mission to defy childhood cancers by supporting the most promising research to find cures and better treatments for all childhood cancers. As a leader in the pediatric cancer community, St. Baldrick’s works tirelessly to ensure that current and future children diagnosed with cancer will have access to the most cutting-edge treatment from the best leaders in the pediatric oncology field.