This is the most comprehensive analysis of racial and ethnic differences in patient characteristics and outcome for patients with ES. In univariate analysis, OS was significantly worse for black patients than white non-Hispanic patients. In addition, after controlling for recognized prognostic factors, OS was significantly worse for black, Asian, and white Hispanic patients compared to white non-Hispanic patients. These differences in outcome may broadly reflect socio-economic differences, biologic differences, or a combination of these factors. Socio-economic differences could encompass treatment disparities, delays in diagnosis, differences in protocol adherence, and differences in local control strategies. Biologic differences may include variations in tumor aggressiveness as well as host factors, such as pharmacogenomic differences in drug metabolism.16
The contribution of each of these factors to the observed differences cannot be ascertained using the SEER database and will require further study.
The influence of race and ethnicity on survival of children with cancer has not been fully analyzed.13
Some studies have reported less of an impact of race and ethnicity on outcomes,12, 17
while others have reported clear differences in survival by race and ethnicity.18, 19
For example, poorer outcome for specific types of acute lymphoblastic leukemia have been reported in black and Hispanic children compared to white children.18, 19
As in the current study, the etiology for these differences is not clear and may include a combination of factors such as biological differences and differential access to healthcare. For example, black children were significantly more likely than white children to have higher-risk prognostic features in childhood ALL including certain immunophenotypes and the t(1;19) chromosomal translocation.17
In addition, higher incidence of leukemia8
and fewer cases of the favorable TEL-AML1 translocation were noted among Hispanic children.20
These differences in outcomes reinforce the need to understand these differences and to try to adjust treatment to reduce outcome disparities among racial and ethnic groups.13
This point is particularly important in Ewing sarcoma in which the standard treatment approach has been defined from clinical trials enrolling mainly white non-Hispanic patients. These approaches may not be optimal for patients from other racial or ethnic groups.
While the SEER database allowed for evaluation of a relatively large number of patients with a rare tumor, the use of this database also resulted in a number of major limitations. First, race, ethnicity, and tumor histology could not be confirmed. Second, in order to develop a large enough cohort of patients with different race and ethnicity groups for analysis, we included patients treated in the 1970's. Given that the treatment of ES has evolved since the 1970's, some of our findings may not apply in the setting of current practice. Third, a substantial amount of data is missing from the SEER database. We had intended to evaluate for differences in treatment by race and ethnicity. Unfortunately, data on local control were of limited quality, with approximately half of patients without any apparent local control. Data on the use of chemotherapy and on the use of high-dose chemotherapy with autologous stem cell rescue were also not available.
Tumor size is a recognized prognostic factor in Ewing sarcoma.21–23
Tumor size was not available for approximately half of the analyzed population. Due to these large numbers of missing values, our final model did not control for tumor size. Approximately 90% of patients had complete data for other confounding variables and were included in these final models. In a sensitivity model that also controlled for tumor size, white Hispanic and black patients continued to demonstrate a significantly inferior outcome compared to white non-Hispanic patients. In this sensitivity model, Asian patients did not demonstrate a statistical difference from the reference group. This lack of difference may reflect small patient numbers, particularly since the point estimate of the hazard ratio did not change but the confidence interval widened.
A higher proportion of white Hispanic patients with ES were registered in SEER over the last decade compared to white non-Hispanic patients with ES. This effect might be explained in part by the growing US Hispanic population. Furthermore, the SEER program has been specifically adding more population-based cancer registries with a higher census of Hispanic residents. Since outcomes for patients with ES have improved over time,24
we controlled for the changing demographic of the SEER database by controlling for year of diagnosis.
This study demonstrates differences in OS according to race and ethnicity even after accounting for known prognostic factors in Ewing sarcoma. Although the reasons for these differences remain unknown, several factors suggest that biologic differences may at least contribute to these differences. First, the striking difference in incidence by race suggests a genetic component to this disease. Second, patients other than white non-Hispanic patients were more likely to present with soft tissue rather than bone tumors. Finally, a previous group demonstrated that Japanese patients had a higher frequency of somatic loss of chromosome 19 compared to white patients.25
Further investigations into the biologic and genetic differences in ES tumors according to race and ethnicity are required. Similarly, further studies into possible environmental differences and health care disparities are required to evaluate the role of these factors in explaining the observed outcome differences.
Patient and tumor characteristics in Ewing sarcoma differ by race and ethnicity. Overall survival also differs by race and ethnicity even after controlling for known prognostic factors.