Timing of Local Therapy Affects Survival in Ewing Sarcoma

Purpose: We aimed to investigate the relationship between survival and time to local therapy after initiation of up-front chemotherapy in the treatment of patients with localized Ewing sarcoma. Methods and Materials: The National Cancer Database was queried for patients with localized Ewing sarcoma treated with primary chemotherapy and subsequent local therapy. Kaplan-Meier survival curves were generated for patients initiating local therapy 6 to 15 weeks and ≥16 weeks after chemotherapy initiation. Multivariable binomial logistic regression was used to identify factors associated with prolonged time to local therapy. A multivariable Cox proportional hazards model was used to identify factors associated with overall survival (OS). Results: The final cohort included 1318 patients. A higher proportion of patients initiating local therapy 6 to 15 weeks after chemotherapy initiation versus ≥16 weeks after chemotherapy initiation were ≤21 years old (79.5% vs 72.0%; P =.004). Age >21 years (P <.001; hazard ratio, 1.65; 95% confidence interval, 1.28-2.12), tumor size >8 cm (P =.016), and time to local therapy ≥16 weeks (P =.005; hazard ratio, 1.41; 95% confidence interval, 1.11-1.80) were associated with reduced OS; after review of margin status, negative margins were associated with improved OS compared with gross disease (P =.029). Patients initiating local therapy at 6 to 15 weeks versus ≥16 weeks had a 5-year OS of 78.7% versus 70.4% and a 10-year OS of 70.3% versus 57.1%, respectively (P <.001). The difference in OS according to time to local therapy was particularly more important in patients receiving radiation therapy alone. Age >21 years and treatment by radiation therapy alone were associated with delayed time (>16 weeks) to local therapy, whereas private insurance and income >$48,000 were less likely to be associated with delayed local therapy. Conclusions: Delayed time to local therapy ≥16 weeks after chemotherapy initiation was independently associated with worse survival in patients with localized Ewing sarcoma.