RADIATION-THERAPY IN EWINGS-SARCOMA - AN UPDATE OF THE CESS-86 TRIAL

Purpose: We present an update analysis of the multiinstitutional Ewing 's sarcoma study CESS 86. Methods and Materials: From January 1986 thr ough June 1991, 177 patients with localized Ewing's sarcoma of bone, a ged 25 years or less, were recruited. Chemotherapy consisted of four 9 -week courses of vincristine, actinomycin D, cyclophosphamide, and adr iamycin (VACA) in low-risk tumors (extremity tumors < 100 cm(3)), or v incristine, actinomycin D, ifosfamide, and adriamycin (VAIA) in high-r isk tumors (central tumors and extremity tumors greater than or equal to 100 cm(3)). Local therapy was an individual decision in each patien t and was either radical surgery (amputation, wide resection) or resec tion plus postoperative irradiation with 45 Gy or definitive radiother apy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractiona tion (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionat ed split-course irradiation simultaneously with the VACA/VAIA chemothe rapy (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 progra m was part of the protocol. Results: Forty-four patients (25%) receive d definitive radiotherapy; 39 (22%) had surgery, and 93 (53%) had rese ction plus postoperative irradiation. The overall 5-year survival was 69%. Thirty-one percent of the patients relapsed, 30% after radiothera py, 26% after radical surgery, and 34% after combined local treatment, The better local control after radical surgery (100%) and resection p lus radiotherapy (95%) as compared to definitive radiotherapy (86%) wa s not associated with an improvement in relapse-free or overall surviv al 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 res ults (5-year overall survival of definitively irradiated patients 63% after conventional fractionation and 65% after hyperfractionation; rel apse-free survival 53% vs. 58%; local control 76% vs. 86%, not signifi cant). The six local failures after radiotherapy did not correlate wit h tumor size or response to chemotherapy. Radiation treatment quality (target volume, technique, dosage) was evaluated retrospectively and w as scored as unacceptable in only 1 out of 44 patients (2%) with defin itive radiotherapy. Grade 3-4 complications developed in 4 out of 44 ( 9%) patients after definitive radiotherapy. Conclusions: Under the giv en selection criteria for local therapy, radiation therapy yielded rel apse-free and overall survival figures comparable to radical surgery. Hyperfractionated split-course irradiation simultaneously with multidr ug chemotherapy did not significantly improve local control or surviva l.