title: Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).
abstract: OBJECTIVE
  To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma.
  
  
  METHODS
  Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients).
  
  
  RESULTS
  After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy.
  
  
  CONCLUSIONS
  Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.
authors.affiliation: Cooperative Osteosarkomstudiengruppe (COSS), Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Albert-Schweitzer-Strasse 33, D-48149 Münster, Germany. coss@uni-muenster.de
authors.forename: Beate
authors.initials: B
authors.lastname: Kempf-Bielack
authors.forename: Stefan S
authors.initials: SS
authors.lastname: Bielack
authors.forename: Heribert
authors.initials: H
authors.lastname: Jürgens
authors.forename: Detlev
authors.initials: D
authors.lastname: Branscheid
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: G Ulrich
authors.initials: GU
authors.lastname: Exner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Göbel
authors.forename: Knut
authors.initials: K
authors.lastname: Helmke
authors.forename: Gernot
authors.initials: G
authors.lastname: Jundt
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kabisch
authors.forename: Mathias
authors.initials: M
authors.lastname: Kevric
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Rainer
authors.initials: R
authors.lastname: Kotz
authors.forename: Rainer
authors.initials: R
authors.lastname: Maas
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schwarz
authors.forename: Michael
authors.initials: M
authors.lastname: Semik
authors.forename: Jörn
authors.initials: J
authors.lastname: Treuner
authors.forename: Andreas
authors.initials: A
authors.lastname: Zoubek
authors.forename: Kurt
authors.initials: K
authors.lastname: Winkler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery*; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors