Data-sharing efforts create breakthroughs in pediatric cancer research

Patient data are essential for analyzing diseases and developing new treatments. Since children’s cancers are rare, pediatric oncologists understand that collaboration is critical to test new treatments.

Decades ago, multi-institutional pediatric cancer collaborative groups in different regions of the world were formed to conduct clinical trials. Although cooperative group clinical trials have led to significant advances for children with cancer, the data collected by a single cooperative group are limited to a specific region of the world and not sufficient to analyze rare patient subsets.

Collecting and sharing such data from patients with pediatric cancer from around the world presents an opportunity to make real breakthroughs in a disease. University of Chicago researchers shifted this paradigm by creating several “data commons”— infrastructure that supports making data available to investigators to download, analyze and make new discoveries.

In a recent article published in the Journal of the National Cancer Institute, the researchers reflected on 20 years of work that led to the creation of a model for how to successfully create an ecosystem of international data-sharing that results in scientific progress. 

Progress in neuroblastoma

Susan L. Cohn, MD, Professor of Pediatrics at UChicago, is a highly respected expert in pediatric cancers and blood diseases. She is a leading authority on neuroblastoma, a pediatric cancer that originates in nerve cells found in an embryo or fetus. Despite accounting for about 8% of all cancers in children, it is responsible for about 15% of childhood cancer deaths. Only about 700 new cases are diagnosed in the United States each year.

During her pediatric residency, Cohn encountered Emily, a precocious four-year-old girl who was diagnosed with neuroblastoma. Despite having the best treatments available at the time, Emily did not survive. Her death left a lasting impression on Cohn, who made the decision to devote her career to improving the outcome of children with this deadly cancer.

Neuroblastoma tumors have varied clinical behavior. Cohn conducted laboratory studies to understand why some tumors do not respond to treatment while others are highly curable. She also led efforts to identify factors that are prognostic of patient outcomes and collaborated with other investigators to design and conduct risk-based Children's Oncology Group (COG) clinical trials for children with neuroblastoma. 

These COG studies refined risk classification and led to more tailored treatment approaches, ultimately improving the outcome for patients in North America. However, cooperative groups in other regions of the world were using different risk classifiers to make treatment decisions. “It became clear to me that an international neuroblastoma risk classifier would be needed to directly compare clinical trial results conducted around the globe,” Cohn said.

Two decades ago, Cohn had the opportunity to co-chair the International Neuroblastoma Risk Group (INRG) Task Force with Andrew Pearson, MD, from the United Kingdom, and lead an international group of neuroblastoma experts at a meeting in Whistler, Canada, sponsored by The William Guy Forbeck Research Foundation. 

At this meeting, the task force developed a process for collecting and sharing data from patients diagnosed with neuroblastoma in North America and Australia, Europe, and Japan. In addition, they created a data dictionary to ensure the patient information was defined uniformly. They were able to collate and analyze data on 8,800 patients. The INRG Classification System, which has now been adopted around the world, was established based on the results of the analysis of these data.

Additionally, the task force recognized the data provided an unprecedented resource for the research community. To ensure these data were available to investigators conducting research studies in different regions of the world, they established a data-sharing model. 

Moving into the modern era

Initially, the neuroblastoma data were entered into an Excel spreadsheet. However, with the emergence of more advanced ways of managing and sharing data, Cohn turned to a colleague at the University of Chicago, Samuel L. Volchenboum, MD, PhD, MS, Professor of Pediatrics, to modify the database to an online searchable format. In addition to caring for patients, Volchenboum studies ways to harness computers to enable research and foster innovation using large data sets. 

In 2012, with support from the Forbeck Foundation and the St. Baldrick Foundation, they started working together to systemize and expand the data collection and its access. In 2013, with help from UChicago research informatics expert Robert Grossman, PhD, Frederick H. Rawson Distinguished Service Professor of Medicine, they established the International Neuroblastoma Risk Group Database, a “living” database housed on a website which allowed researchers to easily search for the information they needed, including biospecimen availability. 

The INRG Data Commons has grown significantly and at present contains data on more than 26,000 neuroblastoma patients from around the world. Volchenboum and team are focused on enriching the INRG Commons with additional genomic and biomarker data, extracted electronic health records, and digital medical images to paint an even clearer picture for researchers. 

To date, more than 40 INRG research studies have been performed by investigators, including analyses of rare patients which would not otherwise be possible. 

“Providing data on thousands of neuroblastoma patients to investigators around the world has led to new discoveries that have changed treatment approaches,” Cohn said. “Increasing the information in the data commons with additional types of data will accelerate research and further improve outcomes for children with neuroblastoma.”

The success of the INRG Data Commons has led to the development of the Pediatric Cancer Data Commons (PCDC), which is the flagship project of Volchenboum’s lab, Data for the Common Good. The PCDC currently houses data on over 44,400 patients and includes 16 other cancers and conditions, including rhabdomyosarcoma, germ cell tumors, Hodgkin lymphoma, and acute myelogenous leukemia.

“Pediatric oncology as a success story is really founded on the notion that we can't be successful unless we share,” Volchenboum said. “Children with leukemia in 1960 did not survive, but now 95% of them live. That is because we learned early on that to study something like leukemia, we had to put data together and share it.”

A model for discovery

The international collaboration and data sharing approach developed by the INRG Task Force has not only led to new research discoveries and progress in neuroblastoma, but it is now serving as a model for advancing rare adult malignancies. Cohn remarked that figuring out how to speak the same language and collaborate across the world to collect, house, and share neuroblastoma patient data is proof-of-principle that this networking model will also lead to advances for patients with other rare cancers and conditions.

Volchenboum said, “All of this is traced back to a seed that Sue planted when she started the INRG and this idea of how we can take rare disease data and make it available to the research community.”