Comparative evaluation of local control strategies in localized Ewing sarcoma of bone: A report from the Children's Oncology Group

Abstract

Background Patients with Ewing sarcoma require local primary tumor control with surgery, radiation, or both. Optimal choice of local control for overall and local disease control remains unclear. Methods Patients with localized Ewing sarcoma of bone treated on three consecutive protocols with standard dose 5-drug chemotherapy every 3 weeks were included (n = 465). We used propensity scores to control for differences between local control groups by constructing multivariate models to assess the impact of local control type on clinical endpoints [event-free survival (EFS); overall survival; local failure; distant failure] independent of differences in propensity to receive each local control type. Results Patients treated with surgery were younger (p=0.02) and had more appendicular tumors (p<0.001). Radiation, compared to surgery, had a higher unadjusted risk of any event (HR 1.70; 95% CI 1.18–2.44), death (HR 1.84; 95% CI 1.18–2.85), or local failure (HR 2.57; 95% CI 1.37–4.83). On multivariate analysis, radiation, compared to surgery, had a higher risk of local failure (2.41; 95% CI 1.24–4.68), though there were no significant differences in EFS (HR 1.42; 95% CI 0.94–2.14), overall survival (HR 1.37; 95% CI 0.83–2.26), or distant failure (HR 1.13; 95% CI 0.70–1.84) between local control groups. Conclusions In this large group of similarly treated patients, choice of local control was not significantly related to EFS, overall survival, or distant failure, though risk of local failure was greater for radiation compared to surgery. These data support surgical resection when appropriate, while radiotherapy remains a reasonable alternative in selected patients.

Survival outcome among patients with Ewing’s sarcoma of bones and joints: a population-based cohort study

“…10,28 In a retrospective study on 512 cases, Bacci et al 29 concluded that surgical resection is more ideal than radiation therapy for patients with Ewing's sarcoma of the extremities for whom adequate surgical margins can be achieved. In addition, race, sex and tumor grade were not independent factors after adjusting for different variables in our Cox multivariate regression model.…”

NCCN Guidelines Insights: Bone Cancer, Version 2.2017

“…44 Data from other retrospective analyses suggest that surgery (± postoperative RT) affords better local control than RT alone in patients with localized disease. 47,48 The combined analysis of 1,058 patients treated in the CESS 81, CESS 86, and EICESS-92 trials showed that the rate of local failure was significantly lower after surgery (± postoperative RT) than after definitive RT, whereas the local control rate in the preoperative RT group was comparable to that of the surgery group. 47 The most recent retrospective analysis of sequential studies (INT-0091, INT-0154, or AEWS0031) performed by the COG also demonstrated that definitive RT was associated with a higher risk of local failure than surgery plus RT, but there was no effect on distant failure.…”

“…47 The most recent retrospective analysis of sequential studies (INT-0091, INT-0154, or AEWS0031) performed by the COG also demonstrated that definitive RT was associated with a higher risk of local failure than surgery plus RT, but there was no effect on distant failure. 48 However, definitive RT may be an effective treatment option for patients with tumors in anatomic locations not amenable to surgery with wider resection margins. 49,50 Tumor size and RT dose have been shown to be predictive of local control rates in patients with nonmetastatic Ewing sarcoma treated with chemotherapy and definitive RT.…”

Local Control of Soft Tissue and Bone Sarcomas

“…In a recent prospective clinical trial, surgery achieved a small but statistically significant advantage over XRT with respect to local control of disease. 49 Surgery also has an advantage in that it avoids risks of secondary malignancy caused by radiation, as well as a potential advantage in clarity in surveillance imaging. Nonetheless, if surgery is unlikely to achieve negative margins or carries undue morbidity, XRT remains an effective means for local control.…”

“…52 Nonetheless, recent work has shown small but statistically significant improved local outcomes with surgery over XRT and has led to recent recommendations from the Children's Oncology Group for "surgical resection when appropriate, whereas radiotherapy remains a reasonable alternative in selected patients." 49 (p467) In addition, there is a renewed interest in adjuvant XRT in association with surgery, especially in axial tumors with more challenging surgical margins.…”