title: Pulmonary metastases of stage IIB extremity osteosarcoma and subsequent pulmonary metastases.
abstract: OBJECTIVE
  This study investigated prognostic factors in nonmetastatic high-grade extremity osteosarcoma and the prognosis following resection of subsequent pulmonary metastases, with emphasis on the effect of chemotherapy-induced tumor necrosis.
  
  
  METHODS
  We reviewed 111 consecutive patients with high-grade nonmetastatic extremity osteosarcoma treated with preoperative chemotherapy and surgical resection, with additional review of 36 patients who had subsequent pulmonary metastases resected.
  
  
  RESULTS
  The overall 5-year survival rate was 53%. In resected primary tumors, tumor-free resection margin (P < .001) and increasing chemotherapy-induced tumor necrosis (> 90% threshold, P < .003) correlated with increased metastasis-free survival. Relative risk factors for metastases were as follows: tumor-containing resection margin (most likely to metastasize); poor response to preoperative chemotherapy and/or lack of postoperative chemotherapy (next worse prognosis); and excellent response to preoperative chemotherapy (> or = 90% necrosis) combined with postoperative chemotherapy (best prognosis). The 5-year survival rate following pulmonary metastasis resection was 23%, whereas a 0% 4-year survival rate followed development of bony metastases (P < .001). The extent of tumor necrosis in resected pulmonary metastases did not affect prognosis. Survival was best in patients with three or fewer pulmonary nodules (P < .048), four or fewer recurrent pulmonary nodules (P < .047), unilateral pulmonary metastases (P < .037), or longer intervals between primary tumor resection and metastases (P < .082).
  
  
  CONCLUSIONS
  Intensive preoperative and postoperative chemotherapy combined with complete resection of both primary and metastatic pulmonary osteosarcomas is justified, with a goal of 100% tumor necrosis and excision. Although current treatment regimens allow effective salvage therapy for a few patients with pulmonary metastases, more effective systemic treatment is needed.
authors.affiliation: Department of Orthopaedic Surgery, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1070.
authors.forename: W G
authors.initials: WG
authors.lastname: Ward
authors.forename: K
authors.initials: K
authors.lastname: Mikaelian
authors.forename: F
authors.initials: F
authors.lastname: Dorey
authors.forename: J M
authors.initials: JM
authors.lastname: Mirra
authors.forename: A
authors.initials: A
authors.lastname: Sassoon
authors.forename: E C
authors.initials: EC
authors.lastname: Holmes
authors.forename: F R
authors.initials: FR
authors.lastname: Eilber
authors.forename: J J
authors.initials: JJ
authors.lastname: Eckardt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D002648:Child; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D011013:Pneumonectomy; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate