Risk factors for detectable metastatic disease at presentation in Ewing sarcoma - An analysis of the SEER registry

Abstract

Background: Ewing family of tumors (EFT) represents the second-most common primary bone malignancy in children and adolescents. Approximately 25% of patients have radiographically detectable metastatic disease at presentation and experience poorer five-year survival, yet risk factors for metastatic disease at presentation are poorly characterized. We sought to study patient characteristics associated with metastatic disease upon presentation for patients with EFT.

Methods: We identified EFT cases in the Surveillance, Epidemiology, and End Results Program (SEER) registry from 2004 to 2012. Using univariate analyses and multivariable logistic regression, we explored the relationship between demographic and clinical factors and the presence of detectable metastatic disease at presentation.

Results: Among 870 EFT cases, 35% (n = 304) presented with detectable metastatic disease. These patients were commonly older (>24 years: 28% vs 19%, p = 0.002) and had a primary tumor site in the axial skeleton (56% vs 44%, p < 0.001). After adjusting for all covariates, compared to patients <11 years, those >24 years old faced a two-fold increase in the odds of metastatic disease (OR = 1.99, 95% CI: 1.17-3.38). Axial (OR = 2.31, 95% CI: 1.58-3.37) and "other" (OR = 2.35, 95% CI: 1.15-4.81) tumor locations had more than twice the likelihood of presenting with metastatic disease, compared to extremity tumor sites. Increasing tumor size conferred up to a three-fold increase in odds of metastatic disease (pTrend <0.001).

Conclusions: Advanced age, axial tumor location, and increasing tumor size are associated with increased odds of detectable metastatic disease upon presentation with EFT. Although these characteristics are not modifiable, they provide objective factors that may inform patient counseling of metastatic risk.

Keywords: EFT; Ewing sarcoma; Metastatic disease; Risk factors.