The National Brain Tumor Society (NBTS) and St. Baldrick's Foundation launched a new initiative to catalyze funding for translational research and drug discovery for pediatric brain cancers.
Several leading pediatric oncologists were on hand Sept. 12 at a Washington Press Club news conference to discuss Project Impact: A Campaign to Defeat Pediatric Brain Tumors.
The members will initially seek to raise $1.5 million with an ultimate goal of investing more than $5 million in research funding from different sources, said NBTS CEO David F. Arons, JD.
The announcement coincided with two other reports. On Sept. 16, the CDC issued a statistical update that showed brain cancer has eclipsed leukemia as the leading cause of pediatric cancer deaths. A second report, released Sept. 8 by the American Cancer Society and the Alliance for Childhood Cancer, also showed pediatric cancer death rates have changed very little in recent decades, and many survivors suffer long-term health problems and die prematurely.
“The status quo is not acceptable,” said Arons. “Current market forces create disincentives for investment in pediatric brain tumor drug discovery and development, leaving NCI-funded clinical trial networks as the primary source of drug discovery and clinical development in this field.
“Philanthropic efforts have tried to infuse resources into the pediatric brain tumor research and drug development field, but these efforts have paled in comparison to fundraising pushes for other more prominent and prevalent diseases, making pediatric brain tumors the dark corner of the oncology world. Pediatric brain cancer, especially high-grade gliomas, should be at the top of everyone's list.”
Several interrelated barriers impede research and development, Arons continued, including small patient populations, a lack of solid preclinical models, and the complex basic biology of these tumors, regulatory hurdles, and economic disincentives.
“To overcome these complex challenges...we need to create an equally sophisticated intervention,” said Arons. “It will take an international effort to overcome these barriers.”
Government and private sources “have to carry a heavier load” in terms of funding pediatric cancer research and “yet have been insufficient to fill the gap,” he said, adding that most new drug R&D is focused on adult cancers.
“This is not fair and it is not acceptable... . Our goal is to make history by making childhood cancers history.”
A major component of Project Impact is the Defeat Pediatric Brain Tumors Research Collaborative, an international effort to accelerate research through shared data, information, materials, and other resources. The collaborative initiative will have four research cores that will work simultaneously on what the organizers have identified as the four most critical areas of research.
These will include the Discovery Core, led by Stefan M. Pfister, MD, Professor and Director of Pediatric Neuro-Oncology at the German Cancer Research Center in Heidelberg. It will focus on molecular diagnostics and target discovery. The Biomarker Core (identification and validation; tissue and serum) will be headed by pediatric oncologist Nada Jabado, MD, PhD, Associate Professor of Pediatrics at McGill University and Montreal Children's Hospital. Suzanne J. Baker, PhD, Director of the Brain Tumor Research Division at St. Jude Children's Research Hospital in Memphis, Tenn., will lead the Preclinical Modeling & Drug Screening Core, while the Smart Trials core will be in collaboration with the Pacific Pediatric Neuro-Oncology Consortium, a network of 15 children's hospitals that conduct clinical trials of new treatments for pediatric brain tumors.
An international multidisciplinary effort involving researchers with different expertise, including molecular biology, genetics, preclinical modeling, and clinical trial design will be needed to address these research cores, said Arons.
“We believe that having groups with complementary skills work together in a coordinated effort, sharing data and expertise, and tackling the problem from multiple angles as one team is the starting point for greater and faster progress.”
One of the chief goals of the program will be developing the first-ever standard of care for treating pediatric high-grade gliomas, including diffuse intrinsic pontine gliomas (DIPG)—the deadliest of pediatric brain cancers.
Roger J. Packer, MD, Senior Vice President, Center for Neuroscience and Behavioral Medicine, and Chairman of Neurology at the Children's National Medical Center, Washington, D.C., emphasized the need for research on these tumors.
“Trying to do something for pediatric high-grade gliomas has been extremely frustrating. There has been no change in prognosis in 30 years,” he said. “But now we have molecular tools including, for the first time, a legitimate target.”
According to Packer, new molecular discoveries over the past 3-5 years suggest therapies could be dramatically more effective in the near future.
“Forward momentum must be maintained—from understanding the molecular and genetic underpinnings of these tumors to understanding how these changes drive tumors. Only then might it be possible to develop effective and biologically precise treatments,” he said.
In its Sept. 16 report, the CDC said that while pediatric deaths from all other cancers declined between 1999 and 2014—17 percent for white children and adolescents and 23 percent for African-American children—about one in three deaths were from brain cancer.
Brain cancers accounted for 23.7 percent of deaths in children and adolescents in 1999, but by 2014 these percentages had reversed, with brain cancer becoming the most common site and accounting for 29.9 percent of all childhood cancer deaths.
“This report is a stark reminder that we must redouble our national efforts to find new and more effective treatments for the thousands of children diagnosed each year with pediatric brain tumors,” said Arons.
“Pediatric brain tumors have not become deadlier over the years. Survival rates have stayed relatively flat for decades. The reason that these patients now face the highest mortality rates is because while other areas of oncology have made great strides in recent years, pediatric brain tumor research has not generated advances that have translated into meaningful clinical benefit for the most vulnerable patients.”
The American Cancer Society/Alliance for Childhood Cancer report found that 5-year survival for high-risk neuroblastoma is only 40-50 percent, and zero for DIPG. This is in contrast with an 84 percent combined survival rate for all childhood cancers diagnosed between 2005 and 2011.
Regarding the long-term health of pediatric cancer survivors, the study found high rates of late side effects, susceptibility to chronic conditions, and early death.
More than two in three survivors of childhood cancer treated several decades ago developed chronic conditions and more than one in three survivors aged 35 or older have experienced health effects considered severe or life threatening, including death, according to the report. This rate of severe events is over five times higher than the rate experienced by these survivors' siblings.
“The numbers here tell a compelling story,” said Katherine Sharpe, Senior Vice president of Patient and Caregiver Support for the ACS.
“We have seen significant progress when it comes to developing effective treatments for a variety of pediatric cancer sites and ultimately saving lives. But when we expand our view to look at all pediatric cancers, as well as long-term health and survival, it becomes clear that there are still areas of research where progress is urgently needed.”
Kurt Samson is a contributing writer.
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