Molecular characterization informs prognosis in patients with localized Ewing sarcoma: A report from the Children’s Oncology Group

Gillani R, Shulman DS, DelRocco NJ, Klega K, Han R, Krailo MD, Slack JC, Tanhaemami M, Ward A, Bainer V, Ricker C, Sparks J, Bailey KM, Reed DR, DuBois SG, Leavey P, Mascarenhas L, Grohar PJ, Church AJ, Crompton BD, Janeway KA. Molecular characterization informs prognosis in patients with localized Ewing sarcoma: A report from the Children’s Oncology Group. medRxiv [Preprint]. 2025 Jan 20:2025.01.20.25320840. doi: 10.1101/2025.01.20.25320840. PMID: 39974064; PMCID: PMC11838998.

Identification of discrete sub-groups associated with treatment response and resistance in localized Ewing sarcoma (EWS) remains a challenge. The primary objective of the Children’s Oncology Group biology study AEWS18B1-Q was to perform molecular characterization of a large cohort of patients with localized Ewing sarcoma treated on prospective trials with modern standard of care therapy. We analyzed clinical and molecular features from patients with localized EWS enrolled on AEWS0031, AEWS1031, or INT-0154 frontline trials. All patients had available FFPE tissue, frozen tissue, or whole-genome amplified material. Sequencing was performed for identification of canonical fusions, recurrent copy number alterations (CNAs), and alterations in TP53 and STAG2. Where available, tissue was analyzed for loss of STAG2 protein expression. Molecular features were evaluated for their association with cumulative incidence of relapse in univariate and multivariable analyses.