title: Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas.
abstract: BACKGROUND
  The authors studied a dose-intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high-risk soft tissue sarcomas. The primary objective was estimation of the rate of >or=95% pathologic necrosis.
  
  
  METHODS
  Twenty-five patients with intermediate-grade or high-grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m(2)/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m(2)/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted).
  
  
  RESULTS
  Sixteen patients (64%) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69%. Twenty-one patients (84%) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40%), ifosfamide-induced encephalopathy (24%), and grade 3/4 anemia (64%). Postoperative wound complications requiring a surgical procedure occurred in 20% of patients. The rate of >or=95% pathologic necrosis was 40% (95% confidence interval [95% CI], 21-59%). Estimates of 2-year overall and disease-free survival were 84% (95% CI, 66-100%) and 62% (95% CI, 37-86%), respectively.
  
  
  CONCLUSIONS
  A high rate of >or=95% pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity.
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239, USA. ryanc@ohsu.edu
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ryan
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Montag
authors.forename: Janet R
authors.initials: JR
authors.lastname: Hosenpud
authors.forename: Brian
authors.initials: B
authors.lastname: Samuels
authors.forename: James B
authors.initials: JB
authors.lastname: Hayden
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Hung
authors.forename: Atiya
authors.initials: A
authors.lastname: Mansoor
authors.forename: Terrance D
authors.initials: TD
authors.lastname: Peabody
authors.forename: Arno J
authors.initials: AJ
authors.lastname: Mundt
authors.forename: Samir
authors.initials: S
authors.lastname: Undevia
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D012307:Risk Factors; D012509:Sarcoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D015251:Epirubicin; D007069:Ifosfamide