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.