Recurrence of Ewing sarcoma is most common within 2 years of initial diagnosis (approximately 80%).[1,2] However, late relapses occurring more than 5 years from initial diagnosis are more common in Ewing sarcoma (13%; 95% confidence interval, 9.4-16.5) than in other pediatric solid tumors. The overall prognosis for patients with recurrent Ewing sarcoma is poor; 5-year survival after recurrence is approximately 10% to 15%.[2,4,5]; [Level of evidence: 3iiA] Time to recurrence is the most important prognostic factor. Patients who recurred more than 2 years from initial diagnosis had a 5-year survival of 30% versus 7% for patients who recurred within 2 years.[1,2] Patients with both local recurrence and distant metastases have a worse outcome than patients with either isolated local recurrence or metastatic recurrence alone.[1,2] Isolated pulmonary recurrence was not an important prognostic factor.
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The selection of treatment for patients with recurrent disease depends on many factors, including the site of recurrence and prior treatment, as well as individual patient considerations. Combinations of chemotherapy, such as cyclophosphamide and topotecan or irinotecan and temozolomide with or without vincristine, are active in recurrent Ewing sarcoma and can be considered for these patients.[6,7,8,9,10,11] There is no standardized second-line treatment for relapsed or refractory Ewing sarcoma. One phase II study of topotecan and cyclophosphamide showed a response in 6 of 17 patients with Ewing sarcoma; 16 of 49 patients had a clinical response in a similar trial from Germany.[6,8] In one retrospective series, 20 patients received temozolomide and irinotecan after recurrence. Five patients achieved a complete response and seven patients achieved a partial response. The combination of gemcitabine and docetaxel has achieved objective responses in relapsed Ewing sarcoma.[Level of evidence: 3iiA]; [Level of evidence: 3iiiDiv] High-dose ifosfamide (3 g/m2 /day for 5 days = 15 g/m2) has shown activity in patients who recurred after therapy which included standard ifosfamide (1.8 g/m2 /day for 5 days = 9 g/m2).[Level of evidence: 3iiiDiv]