title: Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial.
abstract: OBJECTIVE
  To improve the poor prognosis of patients with primary disseminated multifocal Ewing sarcomas (PDMES) with a dose-intense treatment concept.
  
  
  METHODS
  From 1999 to 2005, 281 patients with PDMES were enrolled onto the Euro-EWING 99 R3 study. Median age was 16.2 years (range, 0.4 to 49 years). Recommended treatment consisted of six cycles of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE), one cycle of vincristine, dactinomycin, and ifosfamide (VAI), local treatment (surgery and/or radiotherapy), and high-dose busulfan-melphalan followed by autologous stem-cell transplantation (HDT/SCT).
  
  
  RESULTS
  After a median follow-up of 3.8 years, event-free survival (EFS) and overall survival (OS) at 3 years for all 281 patients were 27% +/- 3% and 34% +/- 4% respectively. Six VIDE cycles were completed by 250 patients (89%); 169 patients (60%) received HDT/SCT. The estimated 3-year EFS from the start of HDT/SCT was 45% for 46 children younger than 14 years. Cox regression analyses demonstrated increased risk at diagnosis for patients older than 14 years (hazard ratio [HR] = 1.6), a primary tumor volume more than 200 mL (HR = 1.8), more than one bone metastatic site (HR = 2.0), bone marrow metastases (HR = 1.6), and additional lung metastases (HR = 1.5). An up-front risk score based on these HR factors identified three groups with EFS rates of 50% for score <or= 3 (82 patients), 25% for score more than 3 to less than 5 (102 patients), and 10% for score >or= 5 (70 patients; P < .0001).
  
  
  CONCLUSIONS
  PDMES patients may survive with intensive multimodal therapy. Age, tumor volume, and extent of metastatic spread are relevant risk factors. A score based on these factors may facilitate risk-adapted treatment approaches.
authors.affiliation: St Anna Children's Hospital, SIRP-CCRI Studies and Statistics on Integrated Research and Projects, Children's Cancer Research Institute, Vienna, Austria. ruth.ladenstein@ccri.at
authors.forename: Ruth
authors.initials: R
authors.lastname: Ladenstein
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pötschger
authors.forename: Marie Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.forename: Jeremy
authors.initials: J
authors.lastname: Whelan
authors.forename: Michael
authors.initials: M
authors.lastname: Paulussen
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.forename: Henk
authors.initials: H
authors.lastname: van den Berg
authors.forename: Uta
authors.initials: U
authors.lastname: Dirksen
authors.forename: Lars
authors.initials: L
authors.lastname: Hjorth
authors.forename: Jean
authors.initials: J
authors.lastname: Michon
authors.forename: Ian
authors.initials: I
authors.lastname: Lewis
authors.forename: Alan
authors.initials: A
authors.lastname: Craft
authors.forename: Heribert
authors.initials: H
authors.lastname: Jürgens
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003609:Dactinomycin / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage*; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D007223:Infant; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D007069:Ifosfamide