title: Survival after recurrent osteosarcoma: data from 3 European Osteosarcoma Intergroup (EOI) randomized controlled trials.
abstract: BACKGROUND
  Recurrence after osteosarcoma usually leads to death; thus prognostic factors for survival are of great importance.
  
  
  METHODS
  Between 1983 and 2002, the European Osteosarcoma Intergroup accrued 1067 patients to 3 randomized controlled trials of pre- and post-operative chemotherapy for patients with resectable non-metastatic high-grade osteosarcoma of the extremity. Control treatment in all trials was doxorubicin 75 mg/m² and cisplatin 100mg/m². The comparators were additional high-dose methotrexate (BO02), T10-based multi-drug regimen (BO03) and G-CSF intensified-DC (BO06). Post-recurrence survival (PRS) was investigated on combined data with standard survival analysis methods.
  
  
  RESULTS
  Median recurrence-free survival was 31 months; 8 recurrences were reported more than 5 years after the diagnosis. In 564 patients with a recurrence (median 13 months post-randomisation), there was no difference in post-relapse survival between treatment arms. Patients whose disease recurred within 2 years after randomization had a worse prognosis than those recurring after 2 years. Patients with good initial histological response to pre-operative chemotherapy had a better overall survival after recurrence than poor responders. Local relapse was more often reported after limb-saving procedures (2 versus 8%; amputation versus limb-saving), independent of the primary tumour site. Site of first recurrence (local 20%, lung 62%, "other" 19%) affected survival, as patients recurring with non-lung distant metastases only or any combination of local relapse, lung metastases and non-lung metastases (=group "other") had significantly worse overall survival (local 39%, lung 19%, "other" 9% at 5 years).
  
  
  CONCLUSIONS
  These data describing a large series of patients with recurrent extremity osteosarcoma confirm the relationship between early recurrence and poor survival. There was better PRS in patients after good histological response to pre-operative chemotherapy, or with local-only recurrence.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Jinks
authors.forename: Matthew
authors.initials: M
authors.lastname: Sydes
authors.forename: Vivien H C
authors.initials: VH
authors.lastname: Bramwell
authors.forename: Martine
authors.initials: M
authors.lastname: van Glabbeke
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Grimer
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Lewis
authors.forename: Marianne A
authors.initials: MA
authors.lastname: Nooij
authors.forename: Antonie H M
authors.initials: AH
authors.lastname: Taminiau
authors.forename: Jeremy
authors.initials: J
authors.lastname: Whelan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D012516:Osteosarcoma / Q000188:drug therapy / Q000401:mortality*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents