Improving the standard of therapy for patients with intermediate-risk neuroblastoma

Each year, approximately 750 patients are diagnosed with neuroblastoma in North America, the most common form of cancer in infants less than one year old. Neuroblastoma is a disease that originates in immature nerve tissue in the adrenal gland or the sympathetic ganglia located near the spinal cord. The majority of children with neuroblastoma are diagnosed before the age of five and more than 95% are diagnosed before they turn 10.

Neuroblastoma is notable for its wide range of clinical behavior, and treatment is tailored according to the patient’s predicted risk of relapse (low, intermediate, or high) based on a combination of biomarkers.

The results of the Children’s Oncology Group (COG) ANBL0531 (NCT00499616) clinical trial, Journal of Clinical Oncology, show excellent survival can be maintained in patients with intermediate-risk neuroblastoma with reduction of therapy for subsets of neuroblastoma patients.

“The primary goal of this study was to reduce therapy for subsets of patients with intermediate-risk neuroblastoma using a biology- and response-based algorithm to assign treatment duration while maintaining a three-year overall survival (OS) of more than 95% for the entire cohort,” says Susan Cohn, MD, chief of pediatric hematology/oncology/stem cell transplant and professor of pediatrics at the University of Chicago Medicine. Cohn was the paper's senior author.

A total of 404 eligible patients were enrolled in the study between Oct. 8, 2007 and June 30, 2011. Eligible patients received two, four or eight cycles of chemotherapy based on prognostic markers including: age at diagnosis, stage, histology and genetic features of the tumor, and allelic status of chromosomes 1p and 11q in patients. Duration of therapy was determined by overall response. Cohn and colleagues found that the three-year EFS and OS for the entire study cohort were 83.2% (95% CI: 79.4-87.0%) and 94.9% (95% CI: 92.7-97.2%) respectively.

The refined treatment strategies for specific subsets of intermediate-risk patients that were based on this response- and biology-based algorithm will now serve as the new standard of care for intermediate-risk patients. Extending these results, observation of favorable biology L2 tumors defined by the International Neuroblastoma Risk Group (INRG) staging system, lacking chromosomal aberrations in patients less than 18 months of age is being evaluated in the COG ANBL1232 (NCT02176967) clinical trial.

To harmonize risk group classification and enable the comparison of clinical trials conducted in different regions around the world, the INRG Classification System was established in 2009. Cohn (US), Pearson (UK) and other INRG Task Force investigators from around the world analyzed data from more than 8,800 patients diagnosed between 1990 and 2002 to establish this consensus approach for categorizing pediatric patients into different risk categories for treatment stratification. In collaboration with UChicago Medicine colleague Samuel Volchenboum, MD, PhD, MS, associate professor of pediatrics, Cohn has made data from the original INRG cohort of 8,800 patients available to the neuroblastoma research community through a new ecosystem called the INRG Data Commons. Additional data have been added to the INRG Data Commons after 2002, and currently information from more than 20,000 patients are available for research investigations.

Cohn is now collaborating with Volchenboum, to build the Pediatric Cancer Data Commons, a database that will house data from patients with neuroblastoma and other types of pediatric cancer that will be available to investigators for research studies. Given the rare nature of neuroblastoma and other pediatric cancers, the Pediatric Cancer Data Commons will provide opportunities to conduct research studies never possible before with smaller data sets.

“Pediatric oncologists have been at the forefront of working collaboratively, and over the past 50 years, we have conducted a series of sequential clinical trials testing treatments for pediatric cancer that have resulted in new standards of care and remarkable improvement in outcome,” adds Cohn. “Collating the clinical trial results conducted around the world and linking these clinical data with genomic, imaging, and other data sets in the Pediatric Cancer Data Commons will enable additional research advances that are likely to ultimately change our treatment strategies and further improve the outcome of children with cancer.”

The study, “Maintaining Outstanding Outcomes using Response and Biology-based Therapy for Intermediate-risk Neuroblastoma: A Report From the Children’s Oncology Group Study ANBL0531,” was published in Journal of Clinical Oncology on Aug. 6, 2019.

This study was supported, in part, by the NIH/NCI Grant U10 CA180899 (Children’s Oncology Group Statistics and 39 Data Center), NCTN Operations Center Grant U10 CA180886, and the St. Baldrick’s Foundation.