title: Efficacy of high vs low dose TNF-isolated limb perfusion for locally advanced soft tissue sarcoma.
abstract: OBJECTIVE
  The administration of a high dose of rTNF-alpha (3-4 mg) and Melphalan via isolated limb perfusion (ILP) for patients with locally advanced limb STS was shown to be effective. Reports that a low dose of TNF (1mg) is as effective, led to the adoption of the low dose regimen as the treatment of choice. The purpose of this study was to compare two groups of patients with locally advanced limb STS, that was treated with high and low dose TNF-ILP, in terms of limb preservation.
  
  
  METHODS
  Retrospective study of 41 patients who underwent ILP, with "high dose" (HD) and "low dose" (LD) TNF. ILP/TNF was performed on candidates to either amputation or significantly mutilating surgery without this treatment. In both groups, all patients, with the exception of three in each group, underwent resection of the residual tumor or tumor bed or limb 8-12 weeks after the procedure.
  
  
  RESULTS
  In the HD group, marked tumor softening occurred within 48 h, and in tumors protruding through the skin, hemorrhagic necrosis was evident within 24h. The overall response rate was 65.2%. Five patients achieved a CR and 10 had a PR; in five of these patients >90% necrosis of the tumor occurred. In eight patients, only minimal regression was observed (stabilization of disease). The rate of limb sparing was 69.5%. In the LD group, the overall response rate was 30.7%. CR was achieved in one patient. PR was observed in two. Two patients were lost to follow up. Of the remaining 15 patients, limb preservation was achieved in 53.3%.
  
  
  CONCLUSIONS
  Despite the retrospective comparison and possible selection bias, it is possible to raise the concern that at least some patients may benefit from a higher TNF dose perfusion in ILP for advanced limb STS.
authors.affiliation: Department of Surgery B, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. ido.nachmany@gmail.com
authors.forename: I
authors.initials: I
authors.lastname: Nachmany
authors.forename: A
authors.initials: A
authors.lastname: Subhi
authors.forename: I
authors.initials: I
authors.lastname: Meller
authors.forename: M
authors.initials: M
authors.lastname: Gutman
authors.forename: G
authors.initials: G
authors.lastname: Lahat
authors.forename: O
authors.initials: O
authors.lastname: Merimsky
authors.forename: J M
authors.initials: JM
authors.lastname: Klausner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001132:Arm; D010478:Chemotherapy, Cancer, Regional Perfusion; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007866:Leg; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha