Value of adjuvant radiotherapy in patients with localized Ewing sarcoma at the extremities: Report from the Ewing 2008 trial.

Abstract

11531 Background: In patients with Ewing Sarcoma (EWS), adjuvant radiotherapy is often performed after surgery that could not obtain wide margins or after poor histological response to surgery. However, the benefit of adjuvant radiotherapy needs further investigation. Therefore, we compared event-free survival (EFS) between surgery (SX) alone and SX combined with radiation therapy (RT), performed a subgroup analysis and identified independent prognostic factors. Methods: The data from localized EWS patients with tumors at the extremities that were treated in the Ewing 2008 trial from 2009-2018 were included in this analysis. Patients received induction chemotherapy according to the protocol and then underwent local therapy. Patients receiving SX or adjuvant RT (combined SX/RT) were included in this analysis. Hazard ratios (HRs) (95% Confidence Intervals (CIs)) were calculated using Cox regression. Results: 360 out of 863 patients (41.7%) presented with an EWS at the extremities with 81 tumors at the upper extremity, and 279 tumors at the lower extremity. Most patients were treated with surgery only (223, 61.94%), while 125 patients (34.72%) were treated with SX plus RT. Adjuvant radiotherapy was conducted after a median time of 69 days (1st quartile, 3rd quartile; 54, 109). Median EFS at 5-years for all patients was 0.74 (0.69, 0.80), 0.76 (0.70, 0.83) for patients after surgery only, and 0.73 (0.64, 0.83) after combined RT/SX. After adjusting for sex, age, tumor volume, histological response and surgical margins, the HR for combined RT/SX vs SX alone was 0.69 (0.37, 1.26), p = 0.22. In patients with poor histological response to surgery (≥10% vital tumor cells) and with high tumor volume (≥ 200mL), additional radiotherapy did not decrease the hazards of any event, HR 0.72 (0.25, 2.06), p = 0.54. We identified high tumor volume, poor histological response to surgery as well as intralesional resection of the tumor as independent prognostic factors after adjusting for other known prognostic factors with HRs of 1.73 (1.04, 2.90), p = 0.03; 2.79 (1.69, 4.62), p < 0.0001 and 215.9 (13.17, 3538.61), p = 0.0002, respectively. Surgical complication was not a prognostic factor after adjusting for above mentioned variables, HR 0.85 (0.31, 2.34), p = 0.75. Conclusions: In our cohort, adjuvant radiotherapy was not superior compared to surgery alone in all patients with localized EWS at the extremities and neither in a subgroup of patients with high-risk factors. Poor histological response, intralesional tumor resection as well as high tumor volume were identified as independent negative prognostic factors. Clinical trial information: NCT00987636.