title: Risk factors for local recurrence and metastasis in soft tissue sarcomas of the extremity.
abstract: OBJECTIVE
  We reviewed our institution's experience in treating soft tissue sarcomas of the extremity to identify factors associated with local recurrence, metastasis, and overall survival, to identify patients who may benefit from intensification of therapy.
  
  
  METHODS
  A retrospective analysis was performed for patients who underwent both limb-sparing surgery and external beam radiotherapy for extremity sarcoma. Those who had gross residual disease or who presented with recurrent or metastatic disease were excluded. The Kaplan-Meier product limit and multivariate Cox regression were used to estimate local failure-free probability, distant failure-free probability, and overall survival along with associations with patient, tumor, and treatment characteristics.
  
  
  RESULTS
  One hundred eighty-eight patients were included in the analysis. Twenty-five (13%) and 46 (24%) experienced local and distant recurrence, respectively. Patients with high/intermediate-grade tumors [hazard ratio (HR)=5.63, 95% confidence interval (CI): 1.27-24.89, P=0.023] or with multifocally positive margins (HR=4.27, 95% CI: 1.20-15.24, P=0.026) were more likely to fail locally. Those with a preceding local recurrence (HR=8.58, 95% CI: 3.87-19.04, P<0.0001), high/intermediate-grade tumors (HR=5.68, 95% CI: 1.28-25.25, P=0.023), or no secondary reexcision (HR=2.5, 95% CI: 1.09-5.74, P=0.031) were more likely to develop metastasis. Patients with local recurrence (HR=3.6, 95% CI: 1.77-7.29, P<0.001), metastasis (HR=16.0, 95% CI: 7.93-32.31, P<0.0001), or without secondary reexcision (HR=3.2, 95% CI: 1.27-8.09, P=0.014) had decreased overall survival.
  
  
  CONCLUSIONS
  Patients whose tumor grade or margin status put them at high risk for local failure should be considered for intensification of therapy. Those with a local recurrence should be considered for increased surveillance or systemic therapy, as local failure is associated with subsequent metastasis and decreased survival.
authors.affiliation: University of Michigan Medical School, Ann Arbor, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Sabolch
authors.forename: Mary
authors.initials: M
authors.lastname: Feng
authors.forename: Kent
authors.initials: K
authors.lastname: Griffith
authors.forename: Callie
authors.initials: C
authors.lastname: Rzasa
authors.forename: Laura
authors.initials: L
authors.lastname: Gadzala
authors.forename: Felix
authors.initials: F
authors.lastname: Feng
authors.forename: Janet Sybil
authors.initials: JS
authors.lastname: Biermann
authors.forename: Rashmi
authors.initials: R
authors.lastname: Chugh
authors.forename: Michael
authors.initials: M
authors.lastname: Ray
authors.forename: Edgar
authors.initials: E
authors.lastname: Ben-Josef
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005121:Extremities; D005260:Female; D006801:Humans; D033183:Interdisciplinary Communication; D053208:Kaplan-Meier Estimate; D023821:Limb Salvage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000532:radiotherapy; D016017:Odds Ratio; D010348:Patient Care Team; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012307:Risk Factors; D012509:Sarcoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy*