Second malignancies after ewing tumor treatment in 690 patients from a cooperative German/Austrian/Dutch study

Ann Oncol. 2001 Nov;12(11):1619-30. doi: 10.1023/a:1013148730966.


Background: Ewing tumor treatment involves high cumulative doses of alkylating agents and topoisomerase inhibitors, drugs capable of inducing second cancers. We analyzed the second cancer risk in a large cohort of consistently treated patients.

Patients and methods: Six hundred ninety Ewing tumor patients were treated between 1992 and 1999 with local therapy and vincristine. doxorubicin, ifosfamide and/or cyclophosphamide, and antinomycin D, with or without etoposide as a randomized question. Second cancer incidences were estimated by competing risk analyses; standardized incidence ratios (SIR) in comparison to registry data were compiled.

Results: After a median observation time of 56 months (32 months for survivors), 6 of 690 patients had developed second cancers: MDS/AML, two, ALL/NHL, two, squamous cell carcinoma, one, liposarcoma, one. SIR were increased 20-30 fold in comparison to the general population. The cumulative second cancer risk five years after diagnosis of the Ewing tumor was 0.0093 for the total group, zero for patients without etoposide, and 0.0118 with etoposide. Additional phase II high-dose therapy increased the risk to 0.0398 after five years.

Conclusions: The second cancder risk observed was in the range to be expected in cancer survivors. High-dose therapy, and less markedly, etoposide, may contribute to the overall second cancer risk.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Neoplasms / drug therapy*
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dactinomycin / administration & dosage
  • Dactinomycin / adverse effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Europe
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / adverse effects
  • Incidence
  • Infant
  • Middle Aged
  • Neoplasms, Second Primary / chemically induced*
  • Prospective Studies
  • Radiotherapy Dosage
  • Sarcoma, Ewing / drug therapy*
  • Vincristine / administration & dosage
  • Vincristine / adverse effects


  • Dactinomycin
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Ifosfamide

Supplementary concepts

  • VACA protocol
  • VAIA protocol