title: Metachronous skeletal osteosarcoma in patients treated with adjuvant and neoadjuvant chemotherapy for nonmetastatic osteosarcoma.
abstract: OBJECTIVE
  The prognosis for patients who develop metachronous skeletal osteosarcoma (OS) has been considered grave compared with that for patients with relapse limited to the lungs. We investigated the incidence and outcome of metachronous skeletal OS after initial treatment of the primary tumor.
  
  
  METHODS
  Twenty-three (median age 18.7 years) of 426 patients with nonmetastatic, high-grade primary OS treated at Memorial Sloan-Kettering Cancer Center (New York, NY) between February 1973 and May 2000 developed metachronous skeletal OS. Initial therapy included combination chemotherapy and surgery. Treatment of subsequent relapses consisted of chemotherapy or radiation alone or surgery with or without additional individualized chemotherapy.
  
  
  RESULTS
  The median time from the diagnosis of primary OS to the development of metachronous OS was 1.4 years (range, 0.2 to 11.3 years). Median survival was 1.5 years (95% confidence interval [CI], 0.8 to 6.9 years). Two- and 5-year postmetachronous overall survival was 43.5% (95% CI, 23.2% to 63.7%) and 33% (95% CI, 13% to 53%), respectively. At last follow-up (range, 0.1 to 12.8 years), five (30.4%) patients were alive with no evidence of disease (range, 1.7 to 12.8 years; median, 4.4 years). For 11 patients who developed metachronous OS 24 months or more from initial diagnosis, 5-year postmetachronous survival rate for patients receiving combined modality versus monotherapy was 83% (95% CI, 54% to 100%) and 40% (95% CI, 0% to 83%), respectively.
  
  
  CONCLUSIONS
  In a small subset of patients who developed late metachronous OS, combined-modality therapy with surgery and aggressive chemotherapy may result in long-term postmetachronous survival. This implies that principles used in treatment of primary OS may be applied to patients with late metachronous skeletal OS.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: LeLe
authors.initials: L
authors.lastname: Aung
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.forename: John H
authors.initials: JH
authors.lastname: Healey
authors.forename: Weiji
authors.initials: W
authors.lastname: Shi
authors.forename: Howard T
authors.initials: HT
authors.lastname: Thaler
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Shorter
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Huvos
authors.forename: Paul A
authors.initials: PA
authors.lastname: Meyers
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D020360:Neoadjuvant Therapy; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy*; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome