title: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols.
abstract: OBJECTIVE
  To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas, extending well beyond those of the typical young patient with seemingly localized extremity disease.
  
  
  METHODS
  A total of 1,702 consecutive newly diagnosed patients with high-grade osteosarcoma of the trunk or limbs registered into the neoadjuvant studies of the Cooperative Osteosarcoma Study Group before July 1998 were entered into an analysis of demographic, tumor-related, and treatment-related variables, response, and survival. The intended therapeutic strategy included preoperative and postoperative chemotherapy with multiple agents as well as surgery of all operable lesions.
  
  
  RESULTS
  Axial tumor site, male sex, and a long history of symptoms were associated with poor response to chemotherapy in univariate and multivariate analysis. Actuarial 10-year overall and event-free survival rates were 59.8% and 48.9%. Among the variables assessable at diagnosis, patient age (actuarial 10-year survival > or = 40, 41.6%; < 40, 60.2%; P =.012), tumor site (axial, 29.2%; limb, 61.7%; P <.0001), and primary metastases (yes, 26.7%; no, 64.4%; P <.0001), and for extremity osteosarcomas, also size (> or = one third, 52.5%; < one third, 66.7%; P <.0001) and location within the limb (proximal, 49.3%; other, 63.9%; P <.0001), had significant influence on outcome. Two additional important prognostic factors were treatment related: response to chemotherapy (poor, 47.2%; good, 73.4%; P <.0001) and the extent of surgery (incomplete, 14.6%; macroscopically complete, 64.8%; P <.0001). All factors except age maintained their significance in multivariate testing, with surgical remission and histologic response emerging as the key prognostic factors.
  
  
  CONCLUSIONS
  Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.
authors.affiliation: Klinik und Poliklinik für Kinderheilkunde, Pädiatrische Hämatologie/Onkologie, Universitätsklinikum, Münster, Germany. coss@uni-muenster.de.
authors.forename: Stefan S
authors.initials: SS
authors.lastname: Bielack
authors.forename: Beate
authors.initials: B
authors.lastname: Kempf-Bielack
authors.forename: Günter
authors.initials: G
authors.lastname: Delling
authors.forename: G Ulrich
authors.initials: GU
authors.lastname: Exner
authors.forename: Silke
authors.initials: S
authors.lastname: Flege
authors.forename: Knut
authors.initials: K
authors.lastname: Helmke
authors.forename: Rainer
authors.initials: R
authors.lastname: Kotz
authors.forename: Mechthild
authors.initials: M
authors.lastname: Salzer-Kuntschik
authors.forename: Matthias
authors.initials: M
authors.lastname: Werner
authors.forename: Winfried
authors.initials: W
authors.lastname: Winkelmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Zoubek
authors.forename: Heribert
authors.initials: H
authors.lastname: Jürgens
authors.forename: Kurt
authors.initials: K
authors.lastname: Winkler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery / Q000628:therapy*; D011379:Prognosis; D015996:Survival Rate