title: Determinants of toxicity, patterns of failure, and outcome among adult patients with soft tissue sarcomas of the extremity and superficial trunk treated with greater than conventional doses of perioperative high-dose-rate brachytherapy and external beam radiotherapy.
abstract: OBJECTIVE
  The present study was undertaken to determine factors predictive of toxicity, patterns of failure, and survival in 60 adult patients with soft tissue sarcomas of the extremity and superficial trunk treated with combined perioperative high-dose-rate brachytherapy and external beam radiotherapy.
  
  
  METHODS
  The patients were treated with surgical resection and perioperative high-dose-rate brachytherapy (16 or 24 Gy) for negative and close/microscopically positive resection margins, respectively. External beam radiotherapy (45 Gy) was added postoperatively to reach a 2-Gy equivalent dose of 62.9 and 72.3 Gy, respectively. Adjuvant chemotherapy with ifosfamide and doxorubicin was given to patients with advanced high-grade tumors.
  
  
  RESULTS
  Grade 3 toxic events were observed in 18 patients (30%) and Grade 4 events in 6 patients (10%). No Grade 5 events were observed. A location in the lower limb was significant for Grade 3 or greater toxic events on multivariate analysis (p = .013), and the tissue volume encompassed by the 150% isodose line showed a trend toward statistical significance (p = .086). The local control, locoregional control, and distant control rate at 9 years was 77.4%, 69.5%, and 63.8%, respectively. On multivariate analysis, microscopically involved margins correlated with local control (p = .036) and locoregional control (p = .007) and tumor size correlated with distant metastases (p = .004). The 9-year disease-free survival and overall survival rate was 47.0% and 61.5%, respectively. Multivariate analysis showed poorer disease-free survival rates for patients with tumors >6 cm (p = .005) and microscopically involved margins (p = .043), and overall survival rates decreased with increasing tumor size (p = .011).
  
  
  CONCLUSIONS
  Grade 3 or greater wound complications can probably be decreased using meticulous treatment planning to decrease the tissue volume encompassed by the 150% isodose line, especially in lower limb locations. Microscopically involved margins remain a predictor of local and locoregional failure, despite radiation doses >70 Gy. Patients with tumors ≥6 cm and microscopically involved margins are at high risk of treatment failure and death from the development of distant metastases.
authors.affiliation: Department of Radiation Oncology, Clínica Universidad de Navarra, University of Navarra, Navarre, Spain.
authors.forename: Iñigo
authors.initials: I
authors.lastname: San Miguel
authors.forename: Mikel
authors.initials: M
authors.lastname: San Julián
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cambeiro
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández Sanmamed
authors.forename: Blanca
authors.initials: B
authors.lastname: Vázquez-García
authors.forename: Maria
authors.initials: M
authors.lastname: Pagola
authors.forename: Miren
authors.initials: M
authors.lastname: Gaztañaga
authors.forename: Salvador
authors.initials: S
authors.lastname: Martín-Algarra
authors.forename: Rafael
authors.initials: R
authors.lastname: Martinez-Monge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001918:Brachytherapy / Q000379:methods; D017024:Chemotherapy, Adjuvant / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage; D005121:Extremities; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018365:Neoplasm, Residual; D011832:Radiation Injuries / Q000473:pathology*; D011879:Radiotherapy Dosage; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D060726:Torso; D017211:Treatment Failure; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D004317:Doxorubicin; D007069:Ifosfamide