Tag Archive for: Jeffrey Dome

illustration of diseased kidneys

The future of Wilms tumor therapies: Q&A with Jeffrey Dome, M.D., Ph.D.

illustration of diseased kidneys

Dr. Dome’s mission is to come up with other therapies to treat Wilms tumor.

Conducting Wilms tumor research has placed Children’s National Hospital as the leader in this space. Jeffrey Dome, M.D., Ph.D., talks about the future of Wilms tumor therapies and what excites him about being able to offer different treatment options to this group of patients.

Q: What’s next for Wilms tumor therapy treatments?

A: Something we’ve learned is that we’re reaching the maximum benefit that we can achieve with conventional chemotherapy and have hit a plateau with some of the high-risk Wilms tumors.

If you look at the history of Wilms tumor, we’ve ratcheted up the cure rate by adding more and more chemotherapy agents. We’re now at a point in which patients can’t tolerate having more toxic chemotherapy added to their regimen. Our mission is to come up with other therapies that work differently.

Q: What have you learned that can lead to new therapy options?

A: I was a co-investigator on a National Cancer Institute-funded project called the TARGET study, which entailed sequencing several hundred Wilms tumors to identify genetic mutations that could be druggable. While a wealth of knowledge was gained on the nature of the biology of Wilms tumor, only a minority of Wilms tumors have targetable mutations. We understand what the mutations are, but most are not mutations that lend themselves to drug therapy.

Therefore, we must think about other forms of therapy for Wilms tumor, such as immunotherapy. That’s where the work with the T cells targeting the WT1 protein Wilms tumor cells come into play.

Q: What do the new therapies look like?

A: I think the future of Wilms tumor therapy will be combining the classic chemotherapy and radiation therapy that we’ve used for many years but also adding another component for the patients with the highest risk of relapse, such as immunotherapy.

Up until now, the studies that we’ve conducted using immunotherapy have introduced this treatment very late as a last resort after everything else has failed. We have seen early signals of efficacy and if we can corroborate this in current studies, I believe the future will be to introduce immunotherapy earlier in the treatment course.

There has been success using immunotherapy in other pediatric solid tumors such as neuroblastoma. I believe the prospects for Wilms tumor are also exciting.

 

histological image of Wilms Tumor

Leading Wilms tumor research nationwide: Q&A with Jeffrey Dome, M.D., Ph.D.

histological image of Wilms Tumor

Children’s National has become a resource for patients and families with Wilms tumor.

During the past year, Children’s National Hospital saw nearly 100 patients with Wilms tumor and other less common kidney cancers of childhood, far more than most centers in the country. This is largely due to the reputation the hospital has established for specializing in these diseases. While most patients with Wilms tumor have excellent outcomes, a significant minority of children with kidney cancer do not fare well. Children’s National has become a resource for patients and families with these challenging cancers.

Behind this reputation is Jeffrey Dome, M.D., Ph.D., senior vice president of the Center for Cancer and Blood Disorders and division chief of Oncology at Children’s National, and the team of researchers he leads. For over a decade, he chaired the Children’s Oncology Group Renal Tumor Committee, an opportunity that gave him and his work great exposure.

Dr. Dome shares more on how Children’s National is leading in this space and what the future holds for new, exciting Wilms tumor treatment options.

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

A: The good news is that for the most common type of childhood kidney cancer, Wilms tumor with “favorable histology,” the survival rate is more than 90%, which is an incredible success story. But approximately 25% of children and teens with other types of Wilms tumor and other kidney cancers do not fare as well. We specialize in kidney cancers that are harder to treat, such as anaplastic Wilms tumor, relapsed favorable histology Wilms tumor, bilateral Wilms tumor, clear cell sarcoma of the kidney, malignant rhabdoid tumor and renal cell carcinoma. Because we see a relatively large number of patients, we can draw on our prior experience and observations to recommend the best treatment options.

Q: What’s unique about this research?

A: We have several early-phase clinical trials that are of interest for children with relapsed kidney tumors. Some of these trials are part of research consortia, such as the National Cancer Institute-funded Pediatric Early Phase Clinical Trials Network (PEP-CTN). Other studies have been developed in-house at Children’s National, including a couple of studies using T cells to target pediatric solid tumors. The T cells that have been engineered by the Children’s National Cellular Therapy Laboratory are of particular interest for Wilms tumor because they target a protein called WT1, which is expressed in most Wilms tumors. In fact, WT1 was named after Wilms tumor. We have now had more than 25 patients with relapsed Wilms tumor come from around the country to participate in these studies. Based on early successes, we are continuing this line of research and trying to improve the technology in the current generation of studies.

Jeffrey Dome

Jeffrey Dome, M.D.: Making strides in the fight against pediatric cancer

Jeffrey DomeJeffrey Dome, M.D., Ph.D., senior vice president of the Center for Cancer and Blood Disorders and chief of the Division of Oncology (ranked number 6 in the nation by U.S. News & World Report 2022-23 Best Children’s Hospitals annual rankings) at Children’s National Hospital in Washington, D.C., is an internationally recognized expert on pediatric solid tumors, with an emphasis on kidney tumors and sarcomas. He chaired the Children’s Oncology Group (COG) Renal Tumor Committee, which oversees clinical research on kidney tumors at more than 200 children’s hospitals around the world for more than 10 years. Dr. Dome is currently the Continental President of North America for the International Society of Paediatric Oncology (SIOP) and serves on several medical advisory boards for cancer centers and foundations.

“This is a remarkably exciting time to be in the field of pediatric oncology, with an explosion of knowledge on cancer biology and genetics and the availability of new treatment modalities including molecularly targeted therapy, immunotherapy and devices to improve drug delivery and local control,” says Dome. “I am proud of the multidisciplinary and cross-center collaborations at Children’s National to deliver the latest innovative therapies.”

The team at Children’s National is making strides across all programs to benefit patients with pediatric cancer. A few highlights include:

  • The Brain Tumor lnstitute is one of the most active clinical and translational research programs in the country. Collaborating with other leading institutions, the Brain Tumor Institute is supported by a robust brain tumor bench research program with focused laboratories in medulloblastoma, high-grade glioma, midline diffuse glioma, diffuse intrinsic pontine glioma, low-grade glioma and immunotherapy. The Brain Tumor Institute is leading two national studies, both funded through the Moon Shot lnitiative. In addition, it works closely with the Virginia Tech brain tumor laboratories on the new Children’s National Research & Innovation Campus.
  • Children’s National is the first children’s hospital in the United States with a Focused Ultrasound Program. This pediatric dedicated program includes high-intensity (HIFU) and low-intensity focused ultrasound (LIFU), offering minimally invasive surgical options for children with extra-cranial solid tumors, low-grade brain tumors and novel, potentially life-saving therapy with LIFU-mediated blood-brain barrier disruptions for diffuse intrinsic pontine gliomas.
  • Children’s National has developed multi-antigen specific T cells that have shown success in early phase clinical trials for leukemias, solid tumors and brain tumors. This promising area of research earned a major boost in the form of a $25 million dollar grant from Cancer Grand Challenges, founded in 2020 by Cancer Research UK and the National Cancer Institute in the U.S. This award supported the foundation of NexTGen, a team of scientists and clinicians with expertise in immunology, proteomics, mathematics and more, across eight institutions in the U.S., U.K. and France. The Center for Cancer and Immunology Research at Children’s National is one of the leaders of this effort.
  • The Blood and Marrow Transplantation team, one of the only dedicated pediatric bone marrow transplant programs in the greater Washington, D.C., region, is celebrating its 35th anniversary, with a history of clinical and research accomplishments for both malignant and non-malignant disorders. This program has seen tremendous success in their day 100 transplant-related mortality (TRM). Recently, for the first time, the day 100 TRM average was 0%, meaning that the program did not lose a patient due to transplant complications in the first 100 days – a remarkable achievement in the world of transplantation.
  • The Cancer Genetics Program has grown tremendously in the past few years, reflecting recognition that approximately 10% of childhood cancers have an underlying cancer predisposition. Despite COVID-19, during the past fiscal year, there were 282 patient visits which is a 40% increase from the prior year. The team has developed a collaboration with researchers in the Rare Disease Institute and now can offer studies for patients with Beckwith-Wiedemann syndrome, children with previously undiagnosed developmental delay and children with undiagnosed syndromes. Further, the team was awarded a grant from the Children’s Cancer Foundation to allow testing for those without insurance coverage.
Jeffrey Dome

Q&A with Dr. Jeffrey Dome on his new role as Continental President of SIOP-North America

Jeffrey Dome

In March 2021, Jeffrey Dome, M.D., Ph.D., senior vice president of the Center for Cancer and Blood Disorders at Children’s National Hospital, was elected as the International Society of Paediatric Oncology’s (SIOP) Continental President of North America.

In March 2021, Jeffrey Dome, M.D., Ph.D., senior vice president of the Center for Cancer and Blood Disorders at Children’s National Hospital, was elected as the International Society of Paediatric Oncology’s (SIOP) Continental President of North America.

On October 21-24, the society will hold its 53rd SIOP Annual Congress virtually. During the congress, Dr. Dome will begin his 3-year term as SIOP continental president of North America and will also chair and speak at an educational symposium on current approaches to the treatment of recurrent Wilms tumor.

Dr. Dome attended his very first SIOP meeting in 2005 and was captivated by how regional context influences pediatric cancer treatment. In 2017, he was chair of the local organizing committee for the 49th annual congress in Washington, D.C., and served on the SIOP Board of Directors.  After 15 years of involvement and attending many of the annual meetings, Dr. Dome shares what he looks forward to while serving as continental president of SIOP North America and the legacy he hopes to leave behind.

  1. What does it mean to you to be elected SIOP continental president of North America?

I’m very excited about this role. There are several important societies and organizations in North America that have made a mark on the field of pediatric oncology, but SIOP is unique in its sole focus on childhood cancer and global approach to improving outcomes, as encapsulated by its vision statement: No child should die of cancer: cure for more, care for all.

  1. What excites you most about this role?

In an eye-opening statistic, North America has only about 10% of the global burden of childhood cancer and less than 2% of worldwide childhood cancer deaths.  Although we relentlessly strive to improve childhood cancer outcomes in the United States, what we experience here is just the tip of the iceberg of the worldwide problem. SIOP seeks to make a difference on the international level by improving education, research and access to care for children with cancer around the world. And I’m excited to have a platform to lead North American ambassadors to do that.

Even though North America has a relatively small fraction of the overall childhood cancer cases, we are one of the most well-resourced continents. The question is, how can we use our knowledge, technology and resources to help the rest of the world.  A big part of this role is to make connections and liaisons to move the needle on improving outcomes.

The other thing we’ve learned from a research standpoint is that pediatric cancers are relatively uncommon and are becoming even rarer through molecular classification, which divides cancers into small genetically defined subgroups.  While these advances are tremendously exciting, they require international collaboration to amass a sufficient number of patients to evaluate novel treatment strategies.  My vision for SIOP North America is to be a convener of researchers and connect people around the world to facilitate that work.

  1. What are some of your goals while serving as continental president?

We recently sent a survey to more than 450 SIOP North America members and had a nearly 45% response rate, which I’m told is superb.  This speaks to an excellent level of engagement in SIOP’s mission, with many members volunteering to participate in committees related to research, advocacy and global health. The majority of the respondents to the survey were physicians but improving childhood cancer treatment takes a holistic approach.  One of my main goals is to increase SIOP North American membership to grow the number of nurses, pharmacists, scientists, psychologists, other behavioral health specialists and clinical research coordinators onboard.

I’d like to also identify two to three very specific projects that will impact pediatric cancer care on a global level. There are different ways to do that. We could improve education in different areas around the world (nursing education that we provide to areas that are lacking nursing support, for example). It could be research education and database education for regions of the world that would like to develop more robust research programs. It can also be medical support and developing medical guidelines for oncologists around the world that are adjusted to different levels of resources that are available.

The other goal would be to enhance supportive care and education for cancer care delivery on the global level.

  1. Why is this work important for you?

One of my mentors from when I was a junior faculty member advised me that to be a well-rounded oncologist, one must be familiar with how childhood cancer is treated around the world because different regions have different approaches. There is something to be learned from everyone.  I took that advice to heart and have tried to look beyond the North American approaches.  I think it’s very important to have a global exchange of ideas and serving as continental president of SIOP-North America will enable more to facilitate this dialogue.

  1. What’s the legacy or impact you hope to leave behind?

SIOP North America has a strong and devoted membership but has largely functioned at the level of the individual members.  I hope to bring more structure to the organization to tackle the global challenges of childhood cancer treatment.

Once this structure is in place, I hope to complete two or three SIOP-North America initiatives that have a measurable impact on improving childhood cancer care delivery or outcomes.  The specific projects have yet to be defined but will likely be in the categories of enhancing education, supportive care and facilitating research infrastructure. There’s so much to tackle that if you just look at the overall problem of childhood cancer, it’s overwhelming.  We’re not going to be able to solve everything in three years, but if we could have a few victories and be able to move the needle in some areas, I think that would be a huge success.

SIOP logo

Jeffrey Dome, M.D., elected SIOP Continental President of North America

Jeffrey Dome

“I’m honored to have been elected as president of a society that is a leader in propelling treatment and advocacy for childhood cancer,” Dr. Dome said. “I look forward to working alongside peers who are committed to efforts to improve outcomes for children with cancer globally.”

Jeffrey Dome, M.D., Ph.D., vice president of the Center for Cancer and Blood Disorders at Children’s National Hospital, has been elected as the International Society of Paediatric Oncology’s (SIOP) Continental President of North America.

“I’m honored to have been elected as president of a society that is a leader in propelling treatment and advocacy for childhood cancer,” Dr. Dome said. “I look forward to working alongside peers who are committed to efforts to improve outcomes for children with cancer globally.”

SIOP is the only global multidisciplinary society devoted to pediatric and adolescent cancer. With over 2,600 members worldwide – including doctors, nurses, other health-care professionals, scientists and researchers – the society is dedicated to increasing knowledge about all aspects of childhood cancer.

SIOP will officially welcome Dr. Dome to the position at its Annual Business Meeting in October.

light micrograph of wilms tumor

Evolution of risk stratification for Wilms tumor

light micrograph of wilms tumor

Light micrograph of Wilms tumor.

Wilms tumor is a rare kidney cancer that primarily affects children. Also known as nephroblastoma, it is the most common malignant renal tumor in children. Advances in the treatment of Wilms tumor are some of the great achievements in the field of oncology, improving survival to 90% and decreasing the burden of therapy.

A key factor in the success of Wilms tumor treatment has been improved risk stratification, enabling augmentation or reduction of therapy depending on a patient’s risk of relapse. In a review article in Current Opinion in Pediatrics, Jeffrey Dome, M.D., Ph.D., vice president of the Center for Cancer and Blood Disorders at Children’s National Hospital, Marie V. Nelson, M.D., assistant professor of pediatrics in the Division of Oncology, and their colleagues look at the evolution of clinical and biological factors that have been adopted for Wilms tumor.

The authors found that the original National Wilms Tumor Study Group (NWTSG) and International Society of Pediatric Oncology (SIOP) studies relied solely on tumor stage to define treatment. Over time, however, additional factors were incorporated into the risk stratification schema, allowing for a multifactorial precision medicine approach.

The authors conclude that “the application of new clinical and biological prognostic factors has created unprecedented ability to tailor therapy for Wilms tumor, accompanied with improved outcomes. Current and future trials will continue to enhance precision medicine for Wilms tumor.”

Read the full study in Current Opinion in Pediatrics.

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).

Jeffrey Dome

Treating Wilms Tumor with vincristine and irinotecan

Jeffrey Dome

“The study was impactful because it established the activity of vincristine/irinotecan against Wilms tumor. Based on these findings, this chemotherapy combination will be applied more broadly in the treatment of Wilms tumor,” says study leader Jeffrey S. Dome, M.D, Ph.D.

Wilms tumor, the most common kidney cancer of childhood, may be classified into different subtypes based on its appearance under the microscope. The “favorable histology” subtype is associated with an excellent survival rate of approximately 90%, whereas the “diffuse anaplastic” subtype is associated with survival rates of only 55% for patients with stage II-IV disease.

The Children’s Oncology Group AREN0321 study, led by Jeffrey S. Dome, M.D, Ph.D., vice president of the Center for Cancer and Blood Disorders at Children’s National Hospital, tested the anti-tumor activity of the chemotherapy combination vincristine and irinotecan in patients with metastatic diffuse anaplastic Wilms tumor.

The study also evaluated whether a new treatment regimen containing carboplatin in addition to the currently used agents (vincristine, doxorubicin, cyclophosphamide and etoposide) would improve patient outcomes. The results, published in the March 5th issue of the Journal of Clinical Oncology, showed that the vincristine/irinotecan combination is highly active. Out of the group, 78% of patients who received this combination had an objective tumor response.

The study also demonstrated that additional chemotherapy drugs can reduce the rate of relapse, but it is likely that we have reached the limit of what children can tolerate. “Future gains will likely be made by using agents with novel mechanisms of action, such as immunotherapy and new drugs that target the molecular abnormalities of Wilms tumor cells,” says Dr. Dome.

Moreover, the additional chemotherapy agents improved cancer-free survival rates to levels unprecedented for diffuse anaplastic Wilms tumor. However, the decrease in relapse rate came at the cost of increased toxicity.

“The study was impactful because it established the activity of vincristine/irinotecan against Wilms tumor. Based on these findings, this chemotherapy combination will be applied more broadly in the treatment of Wilms tumor,” Dr. Dome added.

proton center

Johns Hopkins Proton Therapy Center opens in collaboration with Children’s National

proton center

The Center at Sibley offers state-of-the-art, pencil beam proton therapy equipment, as well as next-generation imaging technologies such as dual energy CT-guided treatment that reduces the range of error, and the latest innovation in biomatrix magnetic resonance imaging designed to target moving tumors in organs like the lung and liver.

Pediatric cancer patients in the Greater Washington region now have access to one of the most advanced, lifesaving proton therapy technologies offered in the U.S. The Johns Hopkins Proton Therapy Center opened Oct.28, 2019, at Sibley Memorial Hospital in collaboration with Children’s National Hospital.

The proton collaboration with Children’s National expands an existing collaboration between Children’s National and Johns Hopkins Medicine that established the pediatric radiation oncology program at Sibley, which treats a wide range of children’s cancer. Now, Sibley will offer the only proton center in the Washington D.C. region with a dedicated pediatric team, staff who are trained in pediatrics instead of adult providers who also treat children.

“This collaboration allows us to bring the latest technology to the region and offer the most advanced cancer treatment to help children live better lives,” says Kurt Newman, M.D., president and CEO at Children’s National. “As one of the Top 10 children’s hospitals in the nation, our goal is to ensure that patients and families are receiving the best care possible.”

The Center at Sibley offers state-of-the-art, pencil beam proton therapy equipment, as well as next-generation imaging technologies such as dual energy CT-guided treatment that reduces the range of error, and the latest innovation in biomatrix magnetic resonance imaging designed to target moving tumors in organs like the lung and liver. A large mechanical arm called a gantry can move the beam 360 degrees around the patient, treating the tumor from several angles as it destroys tumor cells layer by layer.

“Proton therapy is an advanced technology that allows radiation to be delivered precisely to cancer tissue,” says Jeffrey Dome, M.D., Ph.D., vice president for Cancer and Blood Disorders at Children’s National. “This provides a significant advantage compared with conventional radiation therapy, especially in children, where sparing the healthy tissue that surrounds the tumor may be critical for normal growth and development. Proton therapy shows great promise to reduce long-term side effects of radiation treatment.”

The Center at Sibley will have a fully integrated research room, which will allow clinical, basic science and medical physics faculty to advance clinical trial research, translational research and technology development research in proton therapy. Leading experts and oncologists will study proton outcomes for sarcoma, gynecological tumors, pancreatic and liver tumors, lymph node cancers and tumors located near the heart and major blood vessels, such as lung or breast cancers. In addition, the researchers will examine how the proton energy that kills cancer cells interacts with non-cancerous cells and tissue surrounding the tumors.

The JJohns Hopkins Proton Therapy Center opens in phases. The first treatment room opened October 2019. The second room is scheduled to open in spring 2020, and the third room and fixed beam research room are scheduled to open in fall 2020.