title: Prognostic significance of histopathologic response to chemotherapy in nonmetastatic Ewing's sarcoma of the extremities.
abstract: OBJECTIVE
  To evaluate more accurately the effectiveness of preoperative chemotherapy in the treatment of patients with Ewing's sarcoma, we studied histopathologically the chemotherapeutic response and correlated it to oncologic outcome.
  
  
  METHODS
  Between June 1983 and December 1989, 68 patients with nonmetastatic Ewing's sarcoma of the extremities were treated at our institute with preoperative chemotherapy (without radiation therapy) and surgery. The specimens were retrospectively evaluated for areas of viable tumor cells and graded from I to III (macroscopic, microscopic, or no residual disease, respectively) in a blinded fashion. Clinical follow-up data were available on all patients for a mean of 60 months (range, 32 to 111).
  
  
  RESULTS
  This histopathologic analysis was strongly correlated with oncologic outcome (P = .004). Patients who demonstrated grade III response (no identifiable viable tumor nodules present) had improved 5-year disease-free survival rates as compared with patients with grade II (microscopic nodes present; P = .023; 90% v 53%) and grade I responses (macroscopic nodules present; P = .0003; 90% v 32%). Patients with grade II necrosis had statistically improved survival rates over those with grade I necrosis (53% v 32%; P = .074).
  
  
  CONCLUSIONS
  This new histopathologic analysis technique for the evaluation of neoadjuvant chemotherapy effectiveness (which does not rely on tumor volume for its assessment) is a valuable prognostic indicator for patients with Ewing's sarcoma treated with surgery. Based on this preliminary report, cases of grade I or II chemotherapeutic tumor response should be considered clinical failures and a different, more aggressive postoperative chemotherapy regimen should be considered.
authors.affiliation: Laboratory for Oncologic Research, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Picci
authors.forename: B T
authors.initials: BT
authors.lastname: Rougraff
authors.forename: G
authors.initials: G
authors.lastname: Bacci
authors.forename: J R
authors.initials: JR
authors.lastname: Neff
authors.forename: L
authors.initials: L
authors.lastname: Sangiorgi
authors.forename: A
authors.initials: A
authors.lastname: Cazzola
authors.forename: N
authors.initials: N
authors.lastname: Baldini
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.forename: M
authors.initials: M
authors.lastname: Mercuri
authors.forename: P
authors.initials: P
authors.lastname: Ruggieri
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D005121:Extremities; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D016019:Survival Analysis; D016896:Treatment Outcome