title: Tumor vascularization and histopathologic regression of soft tissue sarcomas treated with isolated limb perfusion with TNF-α and melphalan.
abstract: BACKGROUND
  Isolated limb perfusion (TM-ILP) achieves high response rates in soft tissue sarcomas (STS). Some tumors show an insufficient association between radiological and pathological response. We investigated STS after TM-ILP with a primary emphasis on histologic regression patterns.
  
  
  METHODS
  In 53 patients with STS, TM-ILP with subsequent tumor resection was performed. Regression was assessed by the Salzer-Kuntschik regression scale. Microvessel density (MVD) of primary biopsies of 37 patients was determined by immunohistochemistry. Tumor regression was correlated with MVD of primary biopsies and other clinico-pathological parameters.
  
  
  RESULTS
  Regression presented mainly as necrosis or fibrosis/sclerosis upon histopathology. MFH, leiomyosarcoma, or clear cell sarcoma (CCS) responded well; whereas liposarcomas, synovial sarcomas, or MPNST were poor responders. MFH often had abundant necrosis; while other STS mainly presented with fibrosis/sclerosis. MVD had no influence on regression grade but modulated histologic regression patterns. Excellent regression demonstrated a trend toward an association with improved survival and local control.
  
  
  CONCLUSIONS
  TM-ILP yielded high response rates in STS. Regression after TM-ILP exhibits MVD-dependent histopathologic patterns and variable efficacy in different sarcoma types. Complete regression seems to be a favorable prognostic factor. A concerted consideration of histopathology and clinical findings may contribute to a better clinical assessment of regression after TM-ILP.
authors.affiliation: Institute of Pathology and Neuropathology, Sarcoma Center, West German Cancer Center, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany. florian.grabellus@uk-essen.de
authors.forename: Florian
authors.initials: F
authors.lastname: Grabellus
authors.forename: Corinna
authors.initials: C
authors.lastname: Kraft
authors.forename: Sien-Yi
authors.initials: SY
authors.lastname: Sheu-Grabellus
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.forename: Lars E
authors.initials: LE
authors.lastname: Podleska
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Lauenstein
authors.forename: Christoph
authors.initials: C
authors.lastname: Pöttgen
authors.forename: Margarethe J
authors.initials: MJ
authors.lastname: Konik
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Schmid
authors.forename: Georg
authors.initials: G
authors.lastname: Taeger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion; D005121:Extremities; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012509:Sarcoma / Q000098:blood supply* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan