Can postoperative radiotherapy be omitted in localized standard-risk Ewing sarcoma? An observational study of the Euro-EWING Group.

Abstract

10518 Background: Uncertainty exists on the most appropriate use of surgery, radiotherapy (RT) or both for treatment of primary Ewing sarcoma (ES). The objective of this study was to assess the impact of postoperative RT on local control in pts with localized ES and good (<10% residual cells) histologic response to chemotherapy (CT). Methods: We analyzed data of all pts included in the EE99-R1 trial (comparing 2 consolidation CT regimens) undergoing surgery after induction CT. Local recurrence (LR) cumulative incidence (CI) was estimated using a competing risk approach. As local therapy was not randomized but tailored to the individual patient and tumor characteristics, impact of RT was assessed in multivariable models, adjusted for possible confounders: country, age, tumor type, site and volume, quality of resection and histologic response. We also evaluated the heterogeneity of RT effect by patient and tumor characteristics (interaction). Results: Among the 599 pts included from 1999 to 2009, 142 (24%) had received postoperative RT. With median follow-up of 6.2 yrs, disease failure was reported in 156 pts, including a LR in 67 (with concomitant metastases in 28), leading to an 8-yr LR-CI = 12% (se 1.4%). Overall survival = 21% (se 5%) 3 yrs after LR (31% in isolated LR). Controlling for possible confounders, the risk of LR was halved in pts treated by surgery + RT (HR=0.43, 95%CI, 0.21-0.88, p=0.02) compared to surgery alone. Postoperative RT had a rather homogeneous positive effect in all studied subgroups. The benefit of RT was very significant in pts with a tumor volume of >200mL at diagnosis and 100% necrosis. Although not significant, we observed a trend for benefit associated with RT in terms of disease-free, event-free and overall survival. Conclusions: LR contributes significantly to disease failures in this standard risk group who experience few systemic failures. Outcome after LR is very poor. Postoperative RT appears to improve local control for all pts. Good histologic response and complete resection of residual mass may not be sufficient criteria to omit RT. Further study of RT in ES is required to assess the balance between benefit and risk (secondary malignancies, functional sequelae). Clinical trial information: NCT00020566.