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

Background: Ewing tumor treatment involves high cumulative doses of alkylat ing agents and topoisomerase inhibitors, drugs capable of inducing second c ancers. We analyzed the second cancer risk in a large cohort of consistentl y treated patients. Patients and methods: Six hundred ninety Ewing tumor patients were treated between 1992 and 1999 with local therapy and vincristine, doxorubicin, ifos famide and/or cyclophosphamide, and antinomycin D, with or without etoposid e as a randomized question. Second cancer incidences were estimated by comp eting risk analyses; standardized incidence ratios (SIR) in comparison to r egistry data were compiled. Results:After a median observation time of 56 months (32 months for survivo rs), 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 can cer risk five years after diagnosis of the Ewing tumor was 0.0093 for the t otal group, zero for patients without etoposide, and 0.0118 with etoposide. Additional phase II high-dose therapy increased the risk to 0.0398 after f ive years. Conclusions: The second cancder risk observed was in the range to be expect ed in cancer survivors. High-dose therapy, and less markedly, etoposide, ma y contribute to the overall second cancer risk.