Extraskeletal Ewing sarcoma in children, adolescents, and young adults. An analysis of three prospective studies of the Cooperative Weichteilsarkomstudiengruppe (CWS)

Pediatr Blood Cancer. 2021 Oct;68(10):e29145. doi: 10.1002/pbc.29145. Epub 2021 Jun 5.


Background: We have analyzed the outcome of patients with localized extraskeletal Ewing sarcoma (EES) treated in three consecutive Cooperative Weichteilsarkomstudiengruppe (CWS) soft tissue sarcoma (STS) studies: CWS-91, CWS-96, and CWS-2002P.

Methods: Patients were treated in CWS-91 with four- (vincristine, dactinomycin, doxorubicin, and ifosfamide [VAIA] or cyclophosphamide [VACA II]) or five-drug (+etoposide [EVAIA]) cycles, in CWS-96 they were randomly assigned to receive VAIA or CEVAIE (+carboplatin and etoposide), and in CWS-2002P with VAIA III plus optional maintenance therapy (MT) with cyclophosphamide and vinblastine. Local therapy consisted of resection and/or radiotherapy (RT).

Results: Two hundred forty-three patients fulfilled the eligibility criteria. The 5-year event-free survival (EFS) and overall survival (OS) were 63% (95% confidence interval [CI] 57-69) and 73% (95% CI 67-79), respectively. The 5-year EFS by study was 64% (95% CI 54-74) in CWS-91, 57% (95% CI 48-66) in CWS-96, and 79% (95% CI 67-91) in CWS-2002P (n.s.). The 5-year OS was 72% (95% CI 62-82) in CWS-91, 70% (95% CI 61-79) in CWS-96, and 86% (95% CI 76-96) in CWS-2002P (n.s.). In CWS-96, 5-year EFS and OS in the VAIA arm versus the CEVAIE were 65% (95% CI 52-81) versus 55% (95% CI 39-76) log-rank p = .13, and 85% (95% CI 75-96) versus 61% (95% CI 45-82), log-rank p = .09.

Conclusion: Our analysis provides interesting information on the treatment and specificities of EES, which can be useful for a better understanding of this rare entity and should be considered in the development of future clinical trials for Ewing sarcoma defined as FET-ETS fusion positive tumors.

Keywords: Ewing sarcoma; extraskeletal; pediatric solid tumors; soft tissue sarcoma.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols
  • Bone Neoplasms* / drug therapy
  • Child
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Etoposide / therapeutic use
  • Humans
  • Ifosfamide / therapeutic use
  • Prospective Studies
  • Sarcoma, Ewing* / drug therapy
  • Vincristine / therapeutic use
  • Young Adult


  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Ifosfamide