title: Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies.
abstract: BACKGROUND
  This critical review aims to summarize published data on limb sparing surgery for extremity soft tissue sarcoma in combination with pre-operative radiotherapy (RT).
  
  
  METHODS
  This review is based on peer-reviewed publications using a PubMed search on the MeSH headings "soft tissue sarcoma" AND "preoperative radiotherapy". Titles and abstracts screened for data including "fraction size AND/OR total dose AND/OR overall treatment time", "chemotherapy", "targeted agents AND/OR tyrosine kinase inhibitors", are collated. Reference lists from some articles have been studied to obtain other pertinent articles. Additional abstracts presented at international sarcoma meetings have been included as well as information on relevant clinical trials available at the ClinicalTrials.gov website.
  
  
  RESULTS
  Data are presented for the conventional regimen of 50-50.4Gy in 25-28 fractions in 5-6 of weeks preoperative external beam RT with respect to the regimen's local control probability compared to surgery alone, as well as acute and late toxicities. The rationale and outcome data for hypofractionated and/or reduced dose regimens are discussed. Finally, combination schedules with conventional chemotherapy and/or targeted agents are summarized.
  
  
  CONCLUSIONS
  Outside the setting of well-designed prospective clinical trials, the conventional 50Gy in 5-6week schedule should be considered as standard. However, current and future studies addressing alternative fraction size, total dose, overall treatment time and/or combination with chemotherapy or targeted agents may reveal regimens of equal or increased efficacy with reduced late morbidities.
authors.affiliation: Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: r.haas@nki.nl.
authors.forename: Rick L M
authors.initials: RL
authors.lastname: Haas
authors.affiliation: Department of Radiotherapy and Physics, Sarcoma Unit, The Royal Marsden Hospital, London, UK.
authors.forename: Aisha B
authors.initials: AB
authors.lastname: Miah
authors.affiliation: Department of Radiation Oncology, Gustave Roussy, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: LePechoux
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: DeLaney
authors.affiliation: Department of Radiation Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital, Boston, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Baldini
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, USA.
authors.forename: Kaled
authors.initials: K
authors.lastname: Alektiar
authors.affiliation: Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
mesh_terms: D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005121:Extremities / Q000528:radiation effects / Q000601:surgery; D005260:Female; D006801:Humans; D023821:Limb Salvage; D008297:Male; D011300:Preoperative Care / Q000379:methods*; D011446:Prospective Studies; D012509:Sarcoma / Q000532:radiotherapy* / Q000601:surgery
keywords: Chemotherapy; Combined modality treatment; Limb Soft Tissue Sarcoma; Preoperative radiotherapy; Surgery; Targeted agents