2ND MALIGNANCIES AFTER TREATMENT FOR EWINGS-SARCOMA - A REPORT OF THECESS-STUDIES

Purpose: During recent years, more intensified systemic and local trea tment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about th e risk of second malignancies (SM) in long-term survivors. We have ana lyzed the second malignancies in patients treated in the German Ewing' s Sarcoma Studies CESS 81 and CESS 86. Materials and Methods: From Jan uary 1981 through June 1991, 674 patients were registered in the two s equential multicentric Ewing's sarcoma trials CESS 81(recruitment peri od 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomy cin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actino mycin D, ifosfamide, and adriamycin) and a total number of four course s, each lasting nine weeks, was recommended by the protocol. Local the rapy in curative patients was either complete surgery (n = 162), surge ry plus postoperative radiotherapy with 36-46Gy (n = 274), or definiti ve radiotherapy with 46-60Gy (n = 212). The median follow-up at the ti me of this analysis was 5.1 years, the maximum follow-up 16.5 years. R esults: The overall survival of all patients including metastatic pati ents was 55% after 5 years, 48% after 10 years, and 37% after 15 years . Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (a = 1), and three were sarc omas. The interval between diagnosis of Ewing's sarcoma and the diagno sis of the SM was 17-78 months for the four AMLs, 96 months for the RI DS and 82-136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 yea rs. Out of five patients with AML/MDS, three died of rapid AML-progres sion, and two are living with disease. Local therapy (surgery vs. surg ery plus postoperative irradiation vs, definitive radiotherapy) had no impact on the frequency of AML/MDS, but local therapy did influence t he risk of secondary sarcomas. All three patients with secondary sarco mas had received radiotherapy; however, all three sarcomas were salvag ed by subsequent treatment and are in clincal remission with a follow- up of 1 month, 4.3 years, and 7.5 years after the diagnosis of the sec ondary sarcoma. Thus far, SM contributed to less than 1% (3/328) of al l deaths in the CESS-studies. Conclusions: The risk of leukemia after treatment for Ewing's sarcoma is probably in the range of 2%. The risk of solid tumors also seems to be low within the first 10 years after treatment and remains in;the range of 5% after 15 years. In the CESS-s tudies, less than 1% of all deaths within the first 10 years after dia gnosis were caused by SM. Effective salvage therapy for secondary sarc omas is feasible. (C) 1998 Elsevier Science Inc.