PROGNOSTIC FACTORS IN PATIENTS WITH LOCALIZED EWINGS-SARCOMA - THE EFFECT ON SURVIVAL OF ACTUAL RECEIVED DRUG DOSE INTENSITY AND OF HISTOLOGIC RESPONSE TO INDUCTION THERAPY

To bring to the fore the most important prognostic factors in Ewing's sarcoma (ES) with current protocols, we studied the classical prognost ic factors, dose intensity (DI) of actual received drugs, age and hist ological response to induction therapy and their correlation in 39 pat ients with localized ES treated from 11/85 to 06/95 to identify eventu al predictors of event-free survival (EFS). Inclusion criteria were ag e 35 yr or less, definitive local treatment by our team and chemothera py including at least 4 drugs: vincristine (VCR), dactinomycin (DACT), doxorubicin (DOXO) cyclophosphamide (CPX). The endpoint was the absen ce of relapse. Parameters related to the status of patients were teste d using the Chi square test or Fisher's exact test. The non parametric Kruskal-Wallis test was used for quantitative data. When necessary st ratified analysis was done using the Mantel Cox rest. With a median fo llowup of 7 yr, overall survival (OS) and EFS were both 67% at 7 yr. A ccording to univariate analysis, the significant predictors of surviva l were the DI of VCR and DACT, the histological response to preoperati ve chemotherapy (CT), the patient's age (< 18 yr DFS: 84%; > 18 yr DFS : 38%). The risk of metastases nas almost tenfold higher in patients w ith low received DI of VCR (DFS 40% versus 95%) and of DACT (DFS 48% v ersus 94%). The prognostic value of primary tumor characteristics (tum oral volume or location) was erased by the comprehensive treatment. Fo llowing multivariate analysis, the actual received DI of VCR (p < 0.02 ) and DACT (p < 0.03) and the histological response to preoperative CT (p < 0.05) were retained as the only significant independent predicto rs of EFS. Taking into account the actual received DI of VCR and DACT, the prognostic value of age disappears. In conclusion, this study poi nts out the main role of the drug DI in ES (particularly VCR and DACT) and of histological response to preoperative CT.