title: Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children's Cancer Group.
abstract: OBJECTIVE
  The specific aims of this study were to improve event-free survival (EFS) in patients with newly diagnosed nonmetastatic osteosarcoma of an extremity using the histologic response to neoadjuvant chemotherapy to determine postoperative chemotherapy; to evaluate a uniform histologic grading system that measures tumor response; and to identify patient characteristics that might influence EFS and survival.
  
  
  METHODS
  Two hundred sixty-eight patients with nonmetastatic osteosarcoma of the extremity were entered between August 1983 and October 1986. Preoperative chemotherapy consisted of four courses of high-dose methotrexate (MTX) and one course of bleomycin, cyclophosphamide, and dactinomycin (BCD). Histologic response to preoperative chemotherapy was determined by morphometric analysis. Good histologic responders (< 5% residual viable tumor) were treated postoperatively with MTX, BCD, and doxorubicin (DOX); poor histologic responders were treated with BCD, DOX, and cisplatin (CDDP).
  
  
  RESULTS
  The 8-year EFS and survival rates were 53% and 60%, respectively. Two hundred six patients had their tumors assessed for histologic response: 28% displayed a good histologic response to preoperative chemotherapy. Good histologic responders had an 8-year postoperative EFS rate of 81% and survival rate of 87%; those with a poor histologic response had an 8-year postoperative EFS rate of 46% and survival rate of 52%. A primary tumor site in the proximal humerus or proximal femur and an elevated serum alkaline phosphatase level were associated with an increased risk of an adverse event, whereas the type of surgical procedure was not.
  
  
  CONCLUSIONS
  EFS and survival appear to be directly related to histologic response to neoadjuvant chemotherapy.
authors.affiliation: Methodist Hospital of Indiana, Indianapolis, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Provisor
authors.forename: L J
authors.initials: LJ
authors.lastname: Ettinger
authors.forename: J B
authors.initials: JB
authors.lastname: Nachman
authors.forename: M D
authors.initials: MD
authors.lastname: Krailo
authors.forename: J T
authors.initials: JT
authors.lastname: Makley
authors.forename: E J
authors.initials: EJ
authors.lastname: Yunis
authors.forename: A G
authors.initials: AG
authors.lastname: Huvos
authors.forename: D L
authors.initials: DL
authors.lastname: Betcher
authors.forename: E S
authors.initials: ES
authors.lastname: Baum
authors.forename: C T
authors.initials: CT
authors.lastname: Kisker
authors.forename: J S
authors.initials: JS
authors.lastname: Miser
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005121:Extremities; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D001761:Bleomycin; D003609:Dactinomycin; D014750:Vincristine; D003520:Cyclophosphamide; D008727:Methotrexate