gms | German Medical Science

The use of combination chemotherapy along with local control by surgery and/or radiotherapy has had a major impact on improving long-term disease-free survival and cure in patients (pts) with localized Ewing tumors. The results of three consecutive Ewing tumor trials of the German Society of Pediatric Oncology and Hematology (GPOH) (CESS 81, CESS 86, EICESS 92) were analyzed for long-term results and prognostic factors.

The event-free survival (EFS) of 659 protocol pts (39.6% female, age <25 years (y) (mean 13.58 y; SD=5.48)) with primary localized non-metastatic Ewing tumor from CESS 81 (94 pts), CESS 86 (210 pts), EICESS 92 (355 pts) was analyzed. The median volume of the primary tumor was 140 ml (mean 265 ml, SD=440 ml). 49% of pts presented with central primary tumor sites. All pts had received systemic combination chemotherapy. For local control, 74.4% had surgery, 75.7%, radiotherapy, of those1/3 definitive radiotherapy and2/3 in combination with surgery. Half of the patients with no relapse had been under observation for at least 10 y post-diagnosis at the time of analysis.

3-y EFS was 0.655 (CI95% +/- .036), 5-y EFS, 0.62 (+/- .037), 10-y EFS, 0.59 (+/- .038). Univariate analysis identified the following negative prognostic factors: tumor volume >100ml (p<.0001), central tumor site (p=.003), age >15 y (p=.0142), and poor histological response to chemotherapy, i.e. >10% viable tumour cells (p=.0001). Patients with surgery achieved a better outcome (p<.0001) whereas radiotherapy was no prognostic factor (p=.7291). On multivariate analysis, histological response (HR=1.96, CI95%1.42-2.69, p<.0001) and tumor volume (HR=1.56, CI95%1.11-2.19, p=.0107) remained determinants. Looking at study affiliation and outcome, EICESS was found to be superior to CESS 81 and 86 in terms of mortality rate (OAS, p=.0253), with a similar trend for EFS (p=.0903). The median period of observation was 6.1 y (range: 1 month-23 y). 85.4% of first relapse(246 pts)occurred within 3 y, 94.3%, within 5 y after diagnosis. 67.1%were metastases, 17.1%, local relapse, and 15.8%, combined local and systemic relapse. 2/3 of second malignancies (9 pts) occurred later than 5 y from diagnosis.

Patients with localized Ewing tumor, with good histological response, small tumor volume, and surgery for local therapy have a very favorable prognosis with up-to-date treatment approach.