Radiation therapy in Ewing's sarcoma: an update of the CESS 86 trial.

We present an update analysis of the multiinstitutional Ewing's sarcoma study CESS 86. From January 1986 through June 1991, 177 patients with localized Ewing's sarcoma of bone, aged 25 years or less, were recruited. Chemotherapy consisted of four 9-week courses of vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) in low-risk (extremity tumors < 100 cm3), or vincristine, actinomycin D, ifosfamide, and adriamycin (VAIA) in high-risk tumors (central tumors and extremity tumors > or = 100 cm3). Local therapy was an individual decision in each patient and was either radical surgery (amputation, wide resection) or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractionation (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionated split-course irradiation simultaneously with the VACA/VAIA chemotherapy (twice daily 1.6 Gy, break of 12 days after 22.4 Gy and 44.8 Gy, total dose and treatment time as for conventional fractionation). For quality assurance in radiotherapy, a central treatment planning program was part of the protocol. Forty-four patients (25%) received definitive radiotherapy; 39 (22%) had surgery, and 93 (53%) had resection plus postoperative irradiation. The overall 5-year survival was 69%. Thirty-one percent of the patients relapsed, 30% after radiotherapy, 26% after radical surgery, and 34% after combined local treatment. The better local control after radical surgery (100%) and resection plus radiotherapy (95%) as compared to definitive radiotherapy (86%) was not associated with an improvement in relapse-free or overall survival because of a higher frequency of distant metastases after surgery (26% vs. 29% vs. 16%). In irradiated patients, hyperfractionated split-course irradiation and conventional fractionation yielded the same results (5-year overall survival of definitively irradiated patients 63% after conventional fractionation and 65% after hyperfractionation; relapse-free survival 53% vs. 58%; local control 76% vs. 86%, not significant). The six local failures after radiotherapy did not correlate with tumor size or response to chemotherapy. Radiation treatment quality (target volume, technique, dosage) was evaluated retrospectively and was scored as unacceptable in only 1 out of 44 patients (2%) with definitive radiotherapy. Grade 3-4 complications developed in 4 out of 44 (9%) patients after definitive radiotherapy. Under the given selection criteria for local therapy, radiation therapy yielded relapse-free and overall survival figures comparable to radical surgery. Hyperfractionated split-course irradiation simultaneously with multidrug chemotherapy did not significantly improve local control or survival.