Impact of Consolidative Radiation on Overall and Progression Free Survival in Pediatric, Adolescent and Young Adult Metastatic Sarcoma

Abstract

To determine the association between consolidative radiation and survival in pediatric, adolescent, and young adult (AYA) metastatic sarcoma MATERIALS/METHODS: Eligible patients included those diagnosed with metastatic bone or soft tissue sarcoma at ≤39 years of age. Patients whose cancer progressed prior to the time of local control were excluded. Consolidative radiation (RT) was defined as RT to all sites of metastatic disease. Kaplan Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Cox proportional hazards was used to account for confounding variables. To adjust for immortal time bias (ITB), end of local control was chosen as a landmark time. Patients (n = 77) had a median age at diagnosis of 14.5 years (range: 1.7-29.7 years). The most common histology was Ewing sarcoma (49%), followed by rhabdomyosarcoma (30%). Median follow up was 28.5 months, without significant difference between patients treated with and without consolidative RT (23.7 vs. 21.5 months, p = 0.270). Median time to completion of consolidative RT from diagnosis was 8.5 months. Ewing sarcoma was more likely to be treated with consolidative RT compared to other histologies (p<0.001). Consolidative RT was associated with improved OS (2yr OS: 81.9% vs. 57.9%, p = 0.009) and PFS (2yr PFS: 71.2% vs. 30%, p = 0.001). On multivariate analysis, after accounting for age, histology, number, and type of metastases (lung, bone or other), consolidative RT remained independently associated with improved OS (hazard ratio (HR):0.36, 95% confidence interval [CI]: 0.17, 0.78, p = 0.010) and improved PFS (HR = 0.34, 95% CI = 0.16, 0.73, p = 0.006). The OS benefit for consolidative RT persisted after adjusting for ITB (1yr OS post-local control: 80.9% vs. 89.7%, p = 0.016). The effect of consolidative RT was validated in a dataset consisting of patients who were diagnosed with localized disease but had metastatic progression (n = 30). In this metachronous population, consolidative RT remained independently associated with improved OS (HR = 0.11, 95% CI = 0.03, 0.51, p = 0.004) after accounting for age. ConsolidativeRT was independently associated with improved OS and PFS in pediatric and AYA patients with metastatic sarcoma at diagnosis. The OS benefit extended to those who underwent consolidative RT for metastatic progression. Future work should evaluate biomarkers to optimize patient selection and timing and dose of consolidative RT.