Between 1983 and 1988, 184 children with
Ewing's sarcoma were enrolled onto Pediatric Oncology Group 8346 (POG 8346). A total of 178 (97%) met eligibility criteria; 6 had pathology other than
Ewing's sarcoma.
Induction chemotherapy of
cyclophosphamide/
doxorubicin (
adriamycin )(C/A) x 12 weeks was followed by local treatment either surgery or
radiation therapy and C/A,
dactinomycin, and
vincristine for 50 weeks. Resection was advised for patients with small primary
tumors if accomplished without functional loss. Forty patients were randomized to receive SF, whole bone radiation to 39.6 Gy plus a 16.2 Gy boost (total 55.8 Gy) or IF 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%) had
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 rate 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 104 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 SF vs. IF. Site of primary
tumor correlated with 5-year EFS: distal extremity 65% (SE 8%), central 63% (SE 10%), proximal extremity 46% (SE 8%), and pelvic-sacral 24% (SE 10%) (p=0.004). Initial
tumor size did not correlate significantly with EFS. Patterns of failure among the 141 localized patients revealed 23% of patients experienced a local failure, while 40% had a systemic failure. The 5-year local control rate 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 randomized 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 local control rates for those with central
tumors 82% (SE 8%), distal extremity 80% (SE 8%), or proximal extremity 69% (SE 9%) (p=0.023). However, 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% (SE 14%), and those with major deviations had a local control of only 16% (SE 15%) (p=0.005). The local failure was within an irradiated volume in 62% of patients, outside the irradiated volume in 24% of cases, while the precise location could not be determined in the remaining 14%.
CONCLUSIONS: As most failures in
Ewing's sarcoma are systemic, improved EFS requires more effective systemic
chemotherapy. Adequate IF
radiotherapy requires treatment to appropriate volumes as defined by MRI imaging and full radiation doses. Pretreatment review of radiologic images with a musculoskeletal radiologist to determine appropriate
tumor volumes, as well as use of
conformal radiotherapy techniques are important for improved outcome.