Molecular characterization to predict outcomes of patients with localized Ewing sarcoma

Identifying discrete subgroups associated with treatment response and resistance in localized Ewing sarcoma (EWS) is a challenge. The Children’s Oncology Group (COG) study AEWS18B1-Q aimed to molecularly characterize patients with localized EWS on prospective frontline COG trials. A total of 351 patients had sufficient tissue, which in most cases was extracted from two FFPE slides. EWS canonical fusions were identified in 80.3% of patients, whereas pathogenic mutations in TP53 and STAG2 were identified in 5.1% and 7.6%, respectively. A total of 63.1% were found to have recurrent copy number alteration (CNA). In univariate analysis, there was an increased cumulative incidence of relapse in patient with TP53 mutations (43% versus 22%; p=0.039), STAG2 mutations (53% versus 21%l p<0.001), and recurrent CNAs (30% versus 16%; p=0.005). In multivariable analysis, STAG2 mutation was the only molecular biomarker that remained prognostic. The authors conclude that EWS patients with STAG2 mutations are at high risk of relapse.