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Cancer Health Center

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Ewing Sarcoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Ewing Sarcoma: Metastatic Tumors

Metastases at diagnosis are detected in approximately 25% of patients.[1] The prognosis of patients with metastatic disease is poor. Current therapies for patients who present with metastatic disease achieve 6-year event-free survival (EFS) of approximately 28% and overall survival (OS) of approximately 30%.[2,3] For patients with lung/pleural metastases only, 6-year EFS is approximately 40% when utilizing bilateral lung irradiation.[2,4] In contrast, patients with bone/bone marrow metastases have a 4-year EFS of approximately 28% and patients with combined lung and bone/bone marrow metastases have a 4-year EFS of approximately 14%.[4,5] Factors such as age older than 14 years, a primary tumor volume of more than 200 mL, more than one bone metastatic site, bone marrow metastases, and additional lung metastases independently predict a poor outcome in patients presenting with metastatic disease.[3]

Standard Treatment Options

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Note: Separate PDQ summaries on Testicular Cancer Treatment and Levels of Evidence for Cancer Screening and Prevention Studies are also available. Benefits Based on fair evidence, screening for testicular cancer would not result in an appreciable decrease in mortality, in part because therapy at each stage is so effective. Magnitude of Effect: Fair evidence of no reduction in mortality. Study Design: Opinions of respected authorities based on clinical experience, descriptive...

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Standard treatment for patients with metastatic Ewing sarcoma utilizing alternating vincristine, doxorubicin, cyclophosphamide, and ifosfamide/etoposide combined with adequate local control measures applied to both primary and metastatic sites often results in complete or partial responses; however, the overall cure rate is 20%.[5,6,7] In the Intergroup Ewing Sarcoma Study, patients with metastatic disease showed no benefit from the addition of ifosfamide and etoposide to a standard regimen of vincristine, doxorubicin, cyclophosphamide, and actinomycin-D.[7] In another Intergroup study, increasing dose intensity of cyclophosphamide, ifosfamide, and doxorubicin did not improve outcome compared with regimens utilizing standard-dose intensity. This regimen increased toxicity and risk of second malignancy without improving EFS or OS.[2]

Systematic use of radiation therapy and surgery for metastatic sites may improve overall outcome in patients with extrapulmonary metastases. In a retrospective data analysis of 120 patients with multifocal metastatic Ewing sarcoma, patients receiving local treatment of both primary tumor and metastases had a better outcome than patients receiving local treatment of primary tumor only or with no local treatment (3-year EFS, 39% vs. 17% and 14%, P < .001).[8] A similar trend for better outcome with irradiation of all sites of metastatic disease was seen in two retrospective analyses of smaller groups of patients receiving radiation therapy to all tumor sites.[9,10] These results must be interpreted with caution. The patients who received local control therapy to all known sites of metastatic disease were selected by the treating investigator, not randomly assigned. Patients with so many metastases that radiation to all sites would result in bone marrow failure were not selected to receive radiation to all sites of metastatic disease. Patients who did not achieve control of the primary tumor did not go on to have local control of all sites of metastatic disease. There was a selection bias such that while all patients in these reports had multiple sites of metastatic disease, the patients who had surgery and/or radiation therapy of all sites of clinically detectable metastatic disease had better responses to systemic therapy and fewer sites of metastasis than patients who did not undergo similar therapy of metastatic sites.

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