Posts

Jeffrey Dome

The impact of surveillance imaging to detect relapse in Wilms tumor patients

Jeffrey Dome

Dr. Jeffrey Dome, M.D., Ph.D., vice president, Center for Cancer and Blood Disorders.

The Children’s Oncology Group published an article in the Journal of Clinical Oncology looking at the impact that surveillance imaging has on patients with Wilms tumor (WT), the most common kidney cancer in children.

Despite the risks and costs, the use of computed tomography (CT) for routine surveillance to detect recurrence in patients with WT has increased in recent years. The rationale for using CT scans rather than chest x-rays (CXR) and abdominal ultrasounds (US) is that CT scans are more sensitive, thereby enabling recurrences to be detected earlier.

In this study, led by Jeffrey S. Dome, M.D., Ph.D, vice president of the Center for Cancer and Blood Disorders at Children’s National Health System, researchers conducted a retrospective analysis of patients enrolled in the fifth National Wilms Tumor Study (NWTS-5) who experienced relapse to determine if relapse detection with CT scan correlates with improved overall survival compared with relapse detection by CXR or abdominal US.

A total of 281 patients with favorable-histology WT (FHWT) were included in the analysis. The key findings of the study were that:

  • Among patients with relapse after completion of therapy, outcome was improved in patients whose relapse was detected by surveillance imaging rather after signs and symptoms developed.
  • A higher disease burden at relapse, defined by the diameter of the relapsed tumor and the number of sites of relapse, was associated with inferior survival.
  • Relapses detected by CT scan were detected earlier and were smaller on average than relapses detected by CXR or US.
  • However, there was no difference in survival between patients whose relapse was detected by CT versus CXR or US.

An analysis of radiation exposure levels showed that surveillance regimes including CT scans have about seven times the radiation exposure compared to regimens including only CXR and US. Moreover, the cost to detect each recurrence reduced by 50 percent when CXR and US are used for surveillance.

“The results of this study will be practice changing,” said Dr. Dome, one of the doctors leading the clinical trial. “The extra sensitivity that CT scans provide compared to CXR and US do not translate to improved survival and are associated with the downsides of extra radiation exposure, cost and false-positive results that can lead to unnecessary stress and medical interventions,” he added. “Although counter-intuitive, the more sensitive technology is not necessarily better for patients.”

In conclusion, the doctors found that the elimination of CT scans from surveillance programs for unilateral favorable histology Wilms tumor is unlikely to compromise survival. However, it could result in substantially less radiation exposure and lower health care costs. Overall, the risk-benefit ratio associated with imaging modalities should be considered and formally studied for all pediatric cancers.

Affiliations

Elizabeth A. Mullen, Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center, Boston, MA; Yueh-Yun Chi and Emily Hibbitts, University of Florida, Gainesville, FL; James R. Anderson, Merck Research Laboratories, North Wales, PA; Katarina J. Steacy, University of Maryland Medical Center, Baltimore, MD; James I. Geller, Cincinnati Children’s Hospital Medical Centre, Cincinnati, OH; Daniel M. Green, St Jude Children’s Research Hospital, Memphis, TN; Geetika Khanna, Washington University School of Medicine, St Louis, MO; Marcio H. Malogolowkin, University of California at Davis Comprehensive Cancer Center, Sacramento, CA; Paul E. Grundy, Stollery Children’s Hospital, University of Alberta, Alberta; Conrad V. Fernandez, University, Halifax, Nova Scotia, Canada; and Jeffrey S. Dome, Children’s National Health System, George Washington University School of Medicine and Health Sciences, Washington, D.C.

Making the grade: Children’s National is nation’s Top 5 children’s hospital

Children’s National rose in rankings to become the nation’s Top 5 children’s hospital according to the 2018-19 Best Children’s Hospitals Honor Roll released June 26, 2018, by U.S. News & World Report. Additionally, for the second straight year, Children’s Neonatology division led by Billie Lou Short, M.D., ranked No. 1 among 50 neonatal intensive care units ranked across the nation.

Children’s National also ranked in the Top 10 in six additional services:

For the eighth year running, Children’s National ranked in all 10 specialty services, which underscores its unwavering commitment to excellence, continuous quality improvement and unmatched pediatric expertise throughout the organization.

“It’s a distinct honor for Children’s physicians, nurses and employees to be recognized as the nation’s Top 5 pediatric hospital. Children’s National provides the nation’s best care for kids and our dedicated physicians, neonatologists, surgeons, neuroscientists and other specialists, nurses and other clinical support teams are the reason why,” says Kurt Newman, M.D., Children’s President and CEO. “All of the Children’s staff is committed to ensuring that our kids and families enjoy the very best health outcomes today and for the rest of their lives.”

The excellence of Children’s care is made possible by our research insights and clinical innovations. In addition to being named to the U.S. News Honor Roll, a distinction awarded to just 10 children’s centers around the nation, Children’s National is a two-time Magnet® designated hospital for excellence in nursing and is a Leapfrog Group Top Hospital. Children’s ranks seventh among pediatric hospitals in funding from the National Institutes of Health, with a combined $40 million in direct and indirect funding, and transfers the latest research insights from the bench to patients’ bedsides.

“The 10 pediatric centers on this year’s Best Children’s Hospitals Honor Roll deliver exceptional care across a range of specialties and deserve to be highlighted,” says Ben Harder, chief of health analysis at U.S. News. “Day after day, these hospitals provide state-of-the-art medical expertise to children with complex conditions. Their U.S. News’ rankings reflect their commitment to providing high-quality care.”

The 12th annual rankings recognize the top 50 pediatric facilities across the U.S. in 10 pediatric specialties: cancer, cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastrointestinal surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology and urology. Hospitals received points for being ranked in a specialty, and higher-ranking hospitals receive more points. The Best Children’s Hospitals Honor Roll recognizes the 10 hospitals that received the most points overall.

This year’s rankings will be published in the U.S. News & World Report’s “Best Hospitals 2019” guidebook, available for purchase in late September.

Jeffrey Dome

New treatment approach shows promise for patients with stage IV Wilms tumor

Jeffrey Dome

“These findings will change clinical practice and improve survival for patients with Wilms tumor whose cancer has spread to the lungs,” says Jeffrey Dome, M.D., Ph.D.

Wilms tumor, which first develops in the kidneys, is the fifth most common cancer in children under 15 years old. While overall outcomes for patients with Wilms tumor are excellent, patients with metastatic disease, with the lung as the most common site of spread, fare worse than patients with localized disease. That’s why a new study showing significantly improved survival rates for patients with stage IV Wilms tumors with lung metastases is making waves in the pediatric oncology community.

The study, “Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children’s Oncology Group AREN0533 Study” – recently published in the Journal of Clinical Oncology with Jeffrey Dome, M.D., Ph.D., vice president for the Center for Cancer and Blood Disorders at Children’s National Health System, as the senior author – assessed whether lung radiation therapy, part of the standard treatment in combination with chemotherapy drugs, can be avoided for patients with complete lung nodule response after six weeks of chemotherapy. Conversely, the study assessed the benefit of adding two additional chemotherapy agents, cyclophosphamide and etoposide, to the treatment regimen for patients with incomplete lung nodule response or tumor loss of heterozygosity (LOH) at chromosomes 1p and 16q, both associated with interior outcomes in previous studies. The results show that:

  • The new approach to therapy resulted in a 4-year overall survival rate of 96 percent, compared to 84 percent on the predecessor study.
  • About 40 percent of patients with Wilms tumor and lung metastases can be spared initial upfront lung radiation and still have outstanding survival. This will decrease the long-term risk of heart toxicity and breast cancer.
  • Patients with incomplete lung nodule response after six weeks of therapy with cyclophosphamide and etoposide had significantly better 4-year event-free survival: 89 percent compared with 75 percent that was expected based on historical data.
  • Intensification of therapy for patients with LOH at 1p and 16q was highly effective: 4-year event-free survival rate improved from 66 percent on the previous study to 100 percent.

“These findings will change clinical practice and improve survival for patients with Wilms tumor whose cancer has spread to the lungs” said Dr. Dome. “The risk-adapted approach to treatment based on tumor biology and tumor response provides a framework for future studies as we come one step closer to achieving 100 percent survival without treatment-associated side effects.”

Catherine-Bollard-SIOP

Advancing cures for pediatric cancer: Highlights from leading Children’s National experts at SIOP 2017

In mid-October 2017, nearly 2,000 clinicians, scientists, nurses, health care professionals and cancer patients and survivors gathered in Washington, D.C., for SIOP 2017, the Annual Congress of the International Society of Paediatric Oncology. For four days, attendees heard from world-renowned experts while exchanging ideas and information, all in the name of advancing cures for childhood cancer.

Hosted in the hometown of Children’s National Health System and chaired by Jeffrey Dome, M.D., Ph.D., Vice President of the Center for Cancer and Blood Disorders and Chief of Oncology at Children’s National Health System, more than 20 doctors and nurses from Children’s National made an impact on participants through a series of widely attended sessions and addresses, including:

  • Symposium lecture on the latest approaches in anti-viral T-cell therapy to improve patient outcomes, given by Catherine Bollard, M.D., M.B.Ch.B.
  • Keynote lecture on DICER1 mutations in pediatric cancer, given by Ashley Hill, M.D., whose study of a rare childhood lung cancer and gene mutations set the stage for a better understanding of microRNA processing gene mutations in the development of pediatric cancer.
  • Education session on new therapies for sarcomas, led by AeRang Kim, M.D., Ph.D., and Karun Sharma, M.D., Ph.D., sharing research on new approaches for local control of sarcomas, such as surgery, radiation and other ablative measures.
  • Education session on new therapies for gliomas, led by Roger J. Packer, M.D., with presentations on immunotherapy from Eugene Hwang, M.D., and targeted therapy by Lindsay Kilburn, M.D.
  • Podium paper presentation on a new method to measure cancer treatment toxicities as reported by the child by Pamela Hinds, Ph.D., RN, FAAN, as well as an education session on advanced care planning, led by Hinds with a presentation from Maureen E. Lyon, Ph.D.

“These sessions and lectures provided a glimpse into the groundbreaking work by SIOP attendees from around the world,” says Dr. Dome. “Children’s National is proud to play an active role in the development of life-saving treatments for children with cancer and our clinicians look forward to another year of revolutionary developments.”

For more on this year’s SIOP, see the Children’s National press release.

  • Jeffrey Dome, M.D., Ph.D., addresses a group of international colleagues at a reception at Children’s National.

    Jeffrey Dome SIOP
  • Catherine Bollard, M.D., M.B.Ch.B., addresses a group of international colleagues at a reception at Children’s National.

    Catherine-Bollard-SIOP
  • Lindsay Kilburn, M.D., engages with peers from around the world at a reception at Children’s National.

    Lindsay-Kilburn-SIOP

Jeffrey Dome

New approach improves pediatric kidney cancer outcomes

Jeffrey Dome

A recent study co-authored by Jeffrey Dome, M.D., Ph.D., Vice President of the Center for Cancer and Blood Disorders at Children’s National Health System, shows that a new approach to treating children diagnosed with bilateral Wilms tumors (BWT) significantly improved event-free survival (EFS) and overall survival (OS) rates after four years when compared to historical rates.

Wilms tumor, also known as nephroblastoma, is the most common pediatric kidney cancer, typically seen in children ages three to four. Compared to patients with unilateral Wilms tumors, children with bilateral Wilms tumors (BWT) have poorer event-free survival (EFS) and are at higher risk for later effects such as renal failure. The treatment of BWT is challenging because it involves surgical removal of the cancer, while preserving as much healthy kidney tissue as possible to avoid the need for an organ transplant.

A new Children’s Oncology Group (COG) study published in the September issue of the Annals of Surgery demonstrated an exciting new approach to treating children diagnosed with BWT that significantly improved EFS and overall survival (OS) rates after four years when compared to historical rates. Jeffrey Dome, M.D., Ph.D., Vice President of the Center for Cancer and Blood Disorders at Children’s National Health System, was co-senior author of this first-ever, multi-institutional prospective study of children with BWT.

Historically, patients with BWT have had poor outcomes, especially if they have tumors with unfavorable histology. In this study, Dr. Dome and 18 other clinical researchers followed a new treatment approach consisting of three chemotherapy drugs before surgery rather than the standard two drug regimen, surgical removal of cancerous tissue within 12 weeks of diagnosis, and postoperative chemotherapy that was adjusted based on histology.

The study found that preoperative chemotherapy expedited surgical treatment, with 84 percent of patients having surgery within 12 weeks of diagnosis. The new treatment approach also vastly improved EFS and OS rates for patients participating in the study. The four-year EFS rate was 82.1 percent, compared to 56 percent on the predecessor National Wilms Tumor Study-5 (NWTS-5) study. The four-year OS rate was 94.9 percent, compared to 80.8 percent on NWTS-5.

“I am very encouraged by these results, which I believe will serve as a benchmark for future studies and lead to additional treatment improvements, giving more children the chance to overcome this diagnosis while sparing kidney tissue,” says Dr. Dome.

A total of 189 patients at children’s hospitals, universities and cancer centers in the United States and Canada participated in this study. These patients will continue to be followed for 10 years to track kidney failure rates. This study was funded by grants from the National Institutes of Health to the Children’s Oncology Group.

SIOP-Kim, Bollard, and Hill

17 Children’s doctors featured at SIOP

SIOP-Kim, Bollard, and Hill

AeRang Kim, M.D., Ph.D., Catherine Bollard, M.D., MBChB, and D. Ashley Hill, M.D. are among the Children’s National experts who will be speaking at the 49th Congress of the International Society of Pediatric Oncology.

This October, thousands of pediatric oncologists, researchers, nurses, allied health professionals, patients and survivors will gather in Washington, D.C., for the 49th Congress of the International Society of Pediatric Oncology (SIOP). Chaired by Jeffrey Dome, M.D., Ph.D., Vice President of the Center for Cancer and Blood Disorders and Chief of Oncology at Children’s National Health System, and Stephen P. Hunger, M.D., of the Children’s Hospital of Philadelphia, the meeting will feature talks by renowned experts in pediatric oncology, including 17 doctors from Children’s National.

Among these expert speakers are AeRang Kim, M.D., Ph.D., pediatric oncologist and Associate Professor of Pediatrics at the George Washington University School of Medicine & Health Sciences, who will present her latest research on new approaches to local control of sarcomas as part of the SIOP Education Day. Dr. Kim focuses on the development of novel agents and devices for pediatric cancer including pre-clinical testing of novel agents, pharmacokinetic analysis, developing innovative methods for toxicity monitoring and clinical trial design.

Also speaking is Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology at Children’s National, Professor of Pediatrics and of Microbiology, Immunology and Tropical Medicine at the George Washington University School of Medicine & Health Sciences and Director of the Program for Cell Enhancement and Technologies for Immunotherapy (CETI). Dr. Bollard will present a talk as part of the SIOP-St. Baldrick’s Symposium on Cell Therapy for Viral Infections.  Her translational research focuses on developing and applying novel cell therapies to improve outcomes for patients with viral infections, cancer and immunologic disorders.

And, D. Ashley Hill, M.D., Chief of the Division of Anatomic Pathology and Professor of Pathology and Pediatrics at the George Washington University School of Medicine & Health Sciences, will be giving a keynote address on DICER1 mutations in pediatric cancer. Dr. Hill first reported the connection between pleuropulmonary blastoma, a rare childhood lung tumor, and mutations in DICER1, setting the stage for our understanding of microRNA processing gene mutations in the development of pediatric cancer.

Other speakers, session chairs and abstract presenters from Children’s National include: