Ewing Sarcoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Ewing Sarcoma: Localized Tumors
Standard Treatment Options
Because most patients with apparently localized disease at diagnosis have occult metastatic disease, multidrug chemotherapy as well as local disease control with surgery and/or radiation is indicated in the treatment of all patients.[1,2,3,4,5,6,7,8] Current regimens for the treatment of localized Ewing sarcoma achieve event-free survival (EFS) and overall survival (OS) of approximately 70% at 5 years after diagnosis.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about treatment of plasma cell neoplasms (including multiple myeloma). It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
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Current standard chemotherapy in the United States includes vincristine, doxorubicin, and cyclophosphamide, also known as VAdriaC or VDC, alternating with ifosfamide and etoposide (IE). The combination of IE has shown activity in Ewing sarcoma, and a large randomized clinical trial and a nonrandomized trial demonstrated that outcome was improved when IE was alternated with VAdriaC.[2,9,10] Dactinomycin is no longer used in the United States but continues to be used in the Euro-Ewing studies. Increased dose intensity of doxorubicin during the initial months of therapy was associated with an improved outcome in a meta-analysis done prior to the standard use of ifosfamide and etoposide. The use of high-dose VAdriaC has shown promising results in small numbers of patients. A single institution study of 44 patients treated with high-dose VAdriaC and IE had an 82% 4-year EFS. However, in an intergroup trial of the Pediatric Oncology Group and the Children's Cancer Group, which compared a dose-intensified chemotherapy regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC/IE) with standard doses of the same regimen, no differences in outcome were observed. Unlike the single institution trial, this trial did not maintain the dose intensity of alkylating agents for the duration of treatment.
In a completed Children's Oncology Group (COG) trial (COG-AEWS0031), 568 patients with newly diagnosed localized extradural Ewing sarcoma were randomly assigned to receive chemotherapy (VAdriaC alternating with IE) given every 2 weeks (interval compression) versus every 3 weeks (standard). Patients randomly assigned to the every 2-week interval of treatment had an improved 5-year EFS (73% vs. 65%, P = .048). There was no increase in toxicity observed with the every 2-week schedule.
Local control can be achieved by surgery and/or radiation. Surgery is generally the preferred approach if the lesion is resectable.[15,16] The superiority of resection for local control has never been tested in a prospective randomized trial. The apparent superiority may represent selection bias. In past studies, smaller more peripheral tumors were more likely to be treated by surgery, and larger, more central tumors were more likely to be treated by radiation therapy. An Italian retrospective study showed that surgery improved outcome only in extremity tumors, although the number of patients with central axis Ewing sarcoma who achieve adequate margins is small. In a series of 39 patients treated at St. Jude Children's Research Hospital, who received both surgery and radiation, the 8-year local failure rate was 5% for patients with negative surgical margins and 17% for those with positive margins. Data for patients with pelvic primary Ewing sarcoma from a North American intergroup trial showed no difference in local control or survival based on local-control modality—surgery alone, radiation therapy alone, or radiation plus surgery.