Patterns of Failure in Pediatric and Young Adult Rhabdomyosarcoma

Abstract

To characterize patterns of failure in pediatric and young adult patients with rhabdomyosarcoma (RMS) from a single institution with over 20 years of experience. Patients diagnosed with RMS from 2000 to 2022 were identified retrospectively. Time to failure was calculated from diagnosis. Local only failure was defined as first failure at the primary site without distant failure. Distant failure was defined as first failure outside of the primary site with or without local failure. Cumulative incidence (CI) of failure was calculated using death as a competing risk. Fine-Gray regression was used to evaluate impact of prognostic factors. Ninety-five patients were eligible. Median age was 7.28 years (range 0 - 35 years), 41% of patients were >10 years old. Median follow up was 33.3 months. Approximately half (n = 47, 49.5%) of the tumors demonstrated alveolar histology. FOXO1 fusion status was available in 76 (80%) patients, of which 7 out of 37 alveolar tumors (18.9%) were FOXO1 fusion negative. The majority of tumors presented with unfavorable primary site (n = 72, 75.8%) and advanced stage (Stage III and IV, n = 72, 75.8%). The 5-yr CI of local only failure and distant failure for the entire cohort was 19.0% (95% CI 11.3, 28.3) and 34.6% (24.0, 45.5%), respectively. The predominant pattern of failure by Group was: Groups 1&2: Local only (5yr CI 14.8%), Group 3: Distant (5yr CI: 25.9%), Group 4: Distant (5yr CI: 67.6%). CI of distant failure by primary site was higher in perianal/gluteal (n = 2/5, 5yr CI 60.0%) and extremity (n = 8/19, 5yr CI 45.9%) sites. Of the 28 distant failures, 10 (36%) also had a local failure component. CI of local only failure by primary site was higher in parameningeal head and neck (n = 6/25, 5yr CI 30%) and bladder/prostate (n = 2/12, 5yr CI 23%) sites. The following were associated with an increased CI of distant failures: increasing age (HR 1.08, p<0.01), alveolar vs. embryonal histology (HR 3.01, p = 0.0095), FOXO1 fusion positive vs. negative (HR 2.8, p = 0.02) and Group IV vs. Groups I/II (HR 7.7, p = 0.0007). FOXO1 fusion and alveolar histology were associated with older age and Group IV, both of which were independently associated with increased distant failure on multivariate analysis. Failures were predominantly distant in older patients and patients with Group IV RMS, both of which were associated with FOXO1 fusion and alveolar histology, highlighting the need to improve therapies in this population. Local only failures were highest in parameningeal head and neck and bladder/prostate primaries, highlighting the need to improve local control strategies at these sites.