Identification of Patients With Localized Ewing Sarcoma at Higher Risk for Local Failure: A Report From the Children's Oncology Group

Abstract

Purpose: To identify clinical and treatment variables associated with a higher risk of local failure in Ewing sarcoma patients treated on recent Children's Oncology Group protocols.

Methods and materials: Data for 956 patients treated with ifosfamide and etoposide-based chemotherapy on INT-0091, INT-0154, and AEWS0031 were analyzed. Local treatment modalities were defined as surgery, definitive radiation therapy (RT), or surgery plus radiation (S+RT). Five-year cumulative incidence of local failure was determined.

Results: The local failure rate for the entire cohort was 7.3%, with a 3.9% rate for surgery, 15.3% for RT (P<.01), and 6.6% for S+RT (P=.12). The local failure incidence was 5.4% for extremity tumors, 13.2% for pelvis tumors (P<.01), 5.3% for axial non-spine tumors (P=.90), 9.1% for extraskeletal tumors (P=.08), and 3.6% for spine tumors (P=.49). The incidence of local failure was 14.8% for extremity tumors and 22.4% for pelvis tumors treated with RT, compared with 3.7% for extremity tumors and 3.9% for pelvis tumors treated with surgery (P≤.01). There was no difference in local failure incidence by local treatment modality for axial non-spine, spine, and extraskeletal tumors. The local failure incidence was 11.9% in patients aged ≥18 years versus 6.7% in patients aged <18 years (P=.02). Age ≥18 years (hazard ratio 1.9, P=.04) and treatment with RT (hazard ratio 2.40, P<.01) remained independent prognostic factors for higher local failure incidence on multivariate analysis. Tumor size (</≥ 8 cm) was available in 40% of patients and did not correlate with local failure incidence.

Conclusions: Local tumor control is excellent and similar between surgery and RT for axial non-spine, spine, and extraskeletal tumors. Age ≥18 years and use of RT, primarily for pelvis and extremity tumors, are associated with the highest risk of local failure. Further efforts should focus on improving outcomes for these patients.

Fig. 1

(a) Five-year cumulative incidence of local failure by local treatment modality. (b) Five-year cumulative incidence of local failure by tumor site. (c) Five-year cumulative incidence of local failure by age. Note all y axes range from 0% to 20%. Abbreviations: RT = radiation therapy; S = surgery.

Fig. 2

(a) Coronal T2 magnetic resonance image of a right lower extremity Ewing sarcoma tumor treated with radiation therapy. The tumor extended 30.0 cm along the right femur and was associated with a soft-tissue mass measuring 23.0 × 22.0 × 12.6 cm. Surgery would involve a non–limb-sparing approach. (b) Axial contrast T1 spoiled gradient magnetic resonance image of a right pelvis Ewing sarcoma tumor treated with radiation therapy. The tumor measured 15.0 × 13.2 × 9.3 cm and extended from the ilium to the superior pubic ramus. Surgery would require a hemipelvectomy.