title: Neoadjuvant treatment improves capsular integrity and the width of the fibrous capsule of high-grade soft-tissue sarcomas.
abstract: BACKGROUND
  Neoadjuvant treatment is thought to improve resection with margin-negative surgery in locally advanced soft-tissue sarcomas (STS). Treatment-induced alterations of the tumor peripheryhave not yet been microscopically evaluated.
  
  
  OBJECTIVE
  This histopathological study compared limb STS with primary resection and those that had undergone neoadjuvant treatment, emphasizing microscopic changes of the fibrous capsule (FC) and reactive zone (RZ) after neoadjuvant treatment.
  
  
  METHODS
  Patients with primary high-grade limb sarcomas (N = 76) which have not previously been treated were included. Of those, 37 were primarily resected and 39 were treated with one of the following neoadjuvant treatment modalities: 7x chemotherapy (CTX), 3x radiotherapy (RT), 15x isolated limb perfusion (ILP), 8x CTX + RT, and 6x CTX + ILP. Sizes of the FC and RZ were microscopically measured, and FC-integrity was documented. Histopathologic regression was expressed as a percent.
  
  
  RESULTS
  Only 35.1% of untreated sarcomas showed an intact FC. We observed significantly higher capsular integrity after treatment (76.9%). Additionally, the average width of the FC (0.21 mm vs. 0.61 mm) and RZ (0.67 mm vs. 1.48 mm) increased significantly. The extent of histopathologic regression showed a correlation with capsular integrity and width. The combination of two treatment modalities (CTX + RT or ILP) showed strongest effects at the tumor periphery.
  
  
  CONCLUSIONS
  Neoadjuvant treatment stabilizes the tumor periphery in STS (e.g., the capsule). Concerning local treatment strategies, these novel histopathologic insights might significantly influence the decision as to whether primary resection is advisable in advanced local soft-tissue sarcoma.
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital of Essen and Sarcoma Center at West German Cancer Center (WTZ), University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany. florian.grabellus@uk-essen.de
authors.forename: F
authors.initials: F
authors.lastname: Grabellus
authors.forename: L E
authors.initials: LE
authors.lastname: Podleska
authors.forename: S-Y
authors.initials: SY
authors.lastname: Sheu
authors.forename: S
authors.initials: S
authors.lastname: Bauer
authors.forename: C
authors.initials: C
authors.lastname: Pöttgen
authors.forename: C
authors.initials: C
authors.lastname: Kloeters
authors.forename: M
authors.initials: M
authors.lastname: Hoiczyk
authors.forename: T C
authors.initials: TC
authors.lastname: Lauenstein
authors.forename: K W
authors.initials: KW
authors.lastname: Schmid
authors.forename: G
authors.initials: G
authors.lastname: Taeger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D010478:Chemotherapy, Cancer, Regional Perfusion; D005121:Extremities; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D060787:Neoplasm Grading; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D060726:Torso; D016896:Treatment Outcome