title: The role of preoperative radiotherapy in nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery.
abstract: OBJECTIVE
  To assess the role of preoperative radiotherapy in patients with nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery and to compare the response of neoadjuvant therapies, local control, and survival with the literature results.
  
  
  METHODS
  Forty-six patients with osteosarcoma of the limbs who were treated within a limb salvage protocol including preoperative radiotherapy and chemotherapy between 1987 and 2002, were retrospectively analyzed. Median age was 17 years (range, 14-66 years). Treatment was started with neoadjuvant chemotherapy. Cisplatin, epidoxorubicin, ifosfamide, and methotrexate were used in different combinations. Preoperative radiotherapy was applied, usually between the second and third cycle of chemotherapy. Radiotherapy was given (35 Gy in 10 fractions) to 44 patients. Two patients were treated with 46 Gy at 2 Gy/day. Definitive surgery was administered after the third course of chemotherapy. Chemotherapy was complete 6 courses postsurgery.
  
  
  RESULTS
  Median follow-up time was 44 months (range, 2-154 months). Forty-four patients had limb-sparing surgery, whereas 2 had amputation. Tumor necrosis rate was >/=90% in 87% of the patients (Huvos Grade 3-4). Two patients had local failures, and 26 patients (56.5%) had distant metastases. The 5-year local control and overall survival rates were 97.5% and 48.4%, respectively. On univariate analysis, age </=18 years, Huvos Grade 4, lower-extremity localization, and surgery within 1 month significantly survived better than the others. On multivariate analysis, Huvos grade (p = 0.01), age (p = 0.01), interval between neoadjuvant chemotherapy and surgery (p = 0.02), and extremity localization (p = 0.02) were significant prognostic factors for actuarial survival. Severe complication developed in 20% of the patients.
  
  
  CONCLUSIONS
  Preoperative radiotherapy helps to increase the chance of extremity-sparing surgery with good local control and necrosis rate when combined with chemotherapy.
authors.affiliation: Department of Radiation Oncology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. faziletonerdincbas@hotmail.com
authors.forename: Fazilet Oner
authors.initials: FO
authors.lastname: Dinçbaş
authors.forename: Sedat
authors.initials: S
authors.lastname: Koca
authors.forename: Nil Molinas
authors.initials: NM
authors.lastname: Mandel
authors.forename: Murat
authors.initials: M
authors.lastname: Hiz
authors.forename: Sergülen
authors.initials: S
authors.lastname: Dervişoğlu
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Seçmezacar
authors.forename: Didem Colpan
authors.initials: DC
authors.lastname: Oksüz
authors.forename: Beyhan
authors.initials: B
authors.lastname: Ceylaner
authors.forename: Burak
authors.initials: B
authors.lastname: Uzel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000671:Amputation, Surgical; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005121:Extremities; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D023821:Limb Salvage; D008297:Male; D015080:Mesna / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D012516:Osteosarcoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D011379:Prognosis; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D015251:Epirubicin; D015080:Mesna; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate