Racial disparities have been described for almost every type of cancer, with the gap in outcomes widening or holding steady between black and white patients in breast, prostate, colorectal, and lung cancers. Much debate has occurred over the causes of these disparities, with most focusing on the overlapping factors of socioeconomic status, access to health care, and compliance with treatments. Underneath these social contributors may lie biological differences as well, such as the increased prevalence of hard-to-treat triple-negative breast cancer in women of African origin. But separating sociology from biology is almost impossible in the large populational studies needed to measure cancer disparities.
However, the pediatric cancer of neuroblastoma may offer a unique exception to this problem. The cancer, which originates in the nerve tissue outside the brain, is the most frequently seen solid tumor in children, with most cases occurring before the age of 5. Because the cancer is rare – roughly 650 new cases are reported each year in the United States – a large-scale study of outcome disparities has been impossible. But through the combined efforts of the Children’s Oncology Group (COG), a coalition of more than 200 clinical sites for administering trials for pediatric cancer, data from over 3,500 children was collected over 9 years.
That data pool was used for the largest-ever study of neuroblastoma disparities, published this week in the Journal of Clinical Oncology. The analysis found that racial disparities do exist for neuroblastoma, with black children (and Native Americans) more likely to die from the disease than white and Hispanic children. But the reasons for that treatment gap may not follow the same formula that are seen in many adult cancers.
“In many cancers, disparities in outcome appear to be largely due to differences in socio-economic status and environment. For example, the lack of ability to be seen by a doctor in a timely manner and get appropriate care significantly impacts survival,” said Susan Cohn, professor of pediatrics at Comer Children’s Hospital and senior author of the study with Tara Henderson, instructor of pediatrics.
“While multiple factors are also likely to contribute to the disparities we observed in children with neuroblastoma, genetic factors are likely to contribute to the increased prevalence of high-risk tumors in the black cohort, which is quite unique.”
Unlike other cancers, which may grow deadlier and harder-to-treat with time, neuroblastoma almost always remains true to its original diagnosis, Cohn said. Based on a variety of clinical factors, children with neuroblastoma are designated as low, medium, or high-risk, and only rarely does that risk assessment change, even without treatment. So unlike other cancers, the delayed diagnosis of neuroblastoma due to poor health care access is an unlikely contributor to racial disparities.
The treatment of high-risk neuroblastoma also largely takes place in a hospital, involving procedures such as intravenous chemotherapy, radiation treatment, and stem cell transplants. With therapies administered under clinical supervision, issues of compliance and access to affordable medication that often enter the disparities discussion are also largely irrelevant.
Eliminating those prime suspects turns the spotlight on biological causes of racial disparities, a hypothesis supported by other findings from the COG study. The incidence of high-risk neuroblastoma was higher for black children (57 percent) compared to white children (44 percent), and clinical predictors of high risk disease such as older age at diagnosis and unfavorable histology were more common in black children. Even after treatment, black children also exhibit more recurrence or progression of their tumor two years or more after the initial diagnosis. These “late-occurring events” suggest that black children are more likely to develop neuroblastoma that is resistant to standard therapy, leaving residual cancer that is harder to treat, Cohn said.
All those signs point to genetics as the culprit, and the next step is searching for the genes that increase the susceptibility of black children to more dangerous forms of neuroblastoma. To do so, Cohn’s group is teaming up with Nancy Cox and Eileen Dolan, professors of medicine at the University of Chicago Medical Center, and using genome-wide association study data from John Maris of the Children’s Hospital of Pennsylvania. Should the genes that predict high-risk disease or chemotherapy resistance be located, clinicians may be able to use that information for personalized, “pharmacogenomic” treatment of neuroblastoma.
“Our long term goal is to utilize this kind of information to develop individualized therapy,” Cohn said. “For example, if you know that a particular patient has a genotype that is associated with resistance to a specific chemotherapeutic agent, you might either modify the dose or treat the patient with a different agent.”
By finding the best treatment strategy for each single patient, the outcome gap between children of different races will hopefully be chipped away one case at a time. And while such a solution may not have the same impact on other cancers where disparities are due more to social factors than biology, the genetics of neuroblastoma may serve as a model for at least putting a dent in those racial gaps.
Henderson, T., Bhatia, S., Pinto, N., London, W., McGrady, P., Crotty, C., Sun, C., & Cohn, S. (2010). Racial and Ethnic Disparities in Risk and Survival in Children With Neuroblastoma: A Children’s Oncology Group Study Journal of Clinical Oncology DOI: 10.1200/JCO.2010.29.6103