Survival outcomes of patients with localized FOXO1 fusion-positive rhabdomyosarcoma treated on recent clinical trials: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group

Background The objective of this analysis was to evaluate the clinical factors influencing survival outcomes in patients with localized (clinical group I-III), FOXO1 fusion-positive rhabdomyosarcoma (RMS). Methods Patients with confirmed FOXO1 fusion-positive RMS who were enrolled on 3 completed clinical trials for localized RMS were included in the analytic cohort. Outcomes were analyzed using the Kaplan-Meier method to estimate event-free survival (EFS) and overall survival (OS), and the curves were compared using the log-rank test. A Cox proportional hazards regression model was used to perform multivariate analysis of prognostic factors that were significant in the univariate analysis. Results The estimated 4-year EFS and OS of 269 patients with localized, FOXO1 fusion-positive RMS was 53% (95% CI, 47%-59%) and 69% (95% CI, 63%-74%), respectively. Univariate analysis revealed that several known favorable clinical characteristics, including age at diagnosis between 1 and 9 years, complete surgical resection, tumor size <= 5 cm, favorable tumor site, absence of lymph node involvement, confinement to the anatomic site of origin, and PAX7-FOXO1 fusion, were associated with improved outcomes. Multivariate analysis identified older age (>= 10 years) and large tumor size (>5 cm) as independent, adverse prognostic factors for EFS within this population, and patients who had both adverse features experienced substantially inferior outcomes. Conclusions Patients with localized, FOXO1 fusion-positive RMS can be further risk stratified based on clinical features at diagnosis, and older patients with large primary tumors have the poorest prognosis.