Multivariate analysis based risk grouping of ewing tumours (ET) with extra-pulmonary metastatic disease (EPMD): Final results from the Euro Ewing 99 study

9562 Background: To identify an effective treatment for patients with EPMD. Methods: 192 patients (pts) were registered. Median age is 15.8 years (yrs) (0.4–49.29). Primary site was extremity in 57 pts and axial/other in 135 pts (40.6% in the pelvis). Tumour volume was ≥ 200 ml in 114pts. Metastatic spread was bone marrow (BM) only in 19 pts, bone only in 93 pts and bone and BM in 79 pts. Six VIDE induction cycles were completed by 168 pts (85%). Local treatment included surgery when possible and/or radiotherapy (Rx) as indicated. Recommended HDT was busulphan (BU) 600 mg/m2 and melphalan (MEL) 140 mg/m2 with PSCR. Median follow up is 4.2 years (range: 1.9–6.6). Results: Partial remission or better was achieved after cycle 6 in 75/116 pts subjected to HDT/SCR (65%). The overall survival at 3 years for all 192 pts is 29% (95% CI=0.04). Significantly favourable univariate factors in the unselected cohort at diagnosis (Dx) were age < 14 yrs (event free survival at 3 yrs (EFS) 37%, p=0.006), BM involvement only (EFS 47%, p=0.024), single bone lesions only (EFS 35%, p=0.009), extremities (EFS 34%, p=0.007) and tumour volume of <200 ml (EFS 47%, p<0.001). For pts receiving BuMel it is noteworthy that 37 pts of <14a and EPMD achieved an EFS of 47% in comparison to older counterparts >14a (EFS 22% (p=0.026). Multivariate analysis identified two major risk factors at Dx: primary tumour volume >200 ml p<0.001 (RR 2.25) and > 5 bone metastases p=0.064 (RR 2.11). In these risk groups the 3 yr EFS was 56% for 35 pts with <200 ml and <5 bone lesions, for 17pts with <200 ml > 5 bone lesions 29%, for 67 pts >200 ml or < 5 bone lesions 19% and extremely dismal for 47 pts with >200 ml and > 5 bone lesions with 7% (p<0.001). Conclusions: Groups with differing prognoses from EPMD have been identified from this prospectively followed cohort. Aggressive treatment with HDT appears effective only for sub groups of patients with EPMD and ET. No significant financial relationships to disclose.