A MULTIDISCIPLINARY STUDY INVESTIGATING RADIOTHERAPY IN EWINGS-SARCOMA - END RESULTS OF POG NUMBER-8346

Purpose: To determine if involved field radiation (IF) is equivalent t o standard whole bone radiation (SF) in local tumor control; to establ ish patterns of failure following treatment; and to determine response , event-free survival (EFS), and overall survival rates from multidisc iplinary therapy in Ewing's sarcoma. Methods and Materials: Between 19 83 and 1988, 184 children with Ewing's sarcoma were enrolled onto Pedi atric Oncology Group 8346 (POG 8346). A total of 178 (97%) met eligibi lity criteria; 6 had pathology other than Ewing's sarcoma. Induction c hemotherapy of cyclophosphamide/doxorubicin (adriamycin)(C/A) x 12 wee ks was followed by local treatment either surgery or radiation therapy and C/A, dactinomycin, and vincristine for 50 weeks. Resection was ad vised for patients with small primary tumors if accomplished without f unctional loss. Forty patients were randomized to receive SF, whole bo ne radiation to 39.6 Gy plus a 16.2 Gy boost (total 55.8 Gy) or LF to 55.8 Gy, and the remainder were assigned to IF radiation. Results: Of 178 eligible patients; 141 (79%) had localized disease and 37 (21%) ha d metastases at presentation. Their 5-year EFS was 51% (SE 5%)and 23% (SE 7%) respectively. The response rate to induction chemotherapy was 88% (28% complete, 60% partial), but after radiotherapy the response r ate increased to 98%. Thirty-seven of the localized patients underwent resection, of whom 16 (43%) required postoperative radiotherapy; the 5-year EFS of these surgical patients was 80% (SE 7%). The remaining 1 04 localized patients were eligible for randomization or assignment to receive radiotherapy; the 5-year EFS of these patients was 41% (SE 5% ), with no significant difference in EFS between those randomized to S F vs. IF. Site of primary tumor correlated with 5-year EFS:;distal ext remity 65% (SE 8%), central 63 % (SE 10 %), proximal extremity 46% (SE 8%), and pelvic-sacral 24% (SE 10%) (p = 0.004). Initial tumor size d id not correlate significantly with EFS. Patterns of failure among the 141 localized patients revealed 23% of patients experienced a local f ailure, while 40% had a systemic failure. The 5-year local control rat e for the surgical patients +/- postoperative radiotherapy was 88% (SE 6%), while for the patients undergoing radiotherapy alone it was 65% (SE 7%). There was no difference in local control between those random ized to SF vs. IF. The 5-year local control rate for the patients with pelvic-sacral tumors was 44% (SE 15%), significantly worse than the l ocal control rates for those with central tumors 82% (SE 8%), distal e xtremity 80% (SE 8%), or proximal extremity 69% (SE 9%) (p = 0.023). H owever, quality of radiotherapy correlated with outcome; Patients who had appropriate radiotherapy had a 5-year local control of 80% (SE 7%) , while those with minor deviations had 5-year local control of 48% (S E 14%), and those,vith major deviations had a local control of only 16 % (SE 15%) (p = 0.005). The local failure was within an irradiated vol ume in 62% of patients, outside the irradiated volume in 24% of cases, while the precise location could not be determined in the remaining 1 4%. Conclusions: As most failures in Ewing's sarcoma are systemic, imp roved EFS requires more effective systemic chemotherapy. Adequate IP r adiotherapy requires treatment to appropriate volumes as defined by MR I imaging and full radiation doses. Pretreatment review of radiologic images with a musculoskeletal radiologist to determine appropriate tum or volumes, as well as use of conformal radiotherapy techniques are im portant for improved outcome. (C) 1998 Elsevier Science Inc.