title: Treatment modifications in tumour necrosis factor-α (TNF)-based isolated limb perfusion in patients with advanced extremity soft tissue sarcomas.
abstract: BACKGROUND
  Tumour necrosis factor-α (TNF) and melphalan based isolated limb perfusion (TM-ILP) is an attractive treatment option for advanced extremity soft tissue sarcomas (STS). This study reports on a 20-year single centre experience and discusses the evolution and changes in methodology since the introduction of TNF in ILP.
  
  
  METHODS
  We performed 306 TM-ILPs in 275 patients with extremity STS. All patients were candidates for amputation or mutilating surgery in order to achieve local control. Clinical response evaluation consisted of clinical examination and magnetic resonance imaging. To evaluate the importance of TNF-dose, treatment results of two periods (1991-2003 high dose (3-4 mg) TNF; 2003-2012 reduced dose (1-2mg) TNF) were compared.
  
  
  RESULTS
  During the study period, more femoral perfusions were done instead of iliac perfusions. Reduction of TNF dose and reduction of total ILP time did not lead to different clinical response rates (70% and 69% for periods 1 and 2 respectively) or different local recurrence rates, but was associated with less local toxicity (23% and 14% for periods 1 and 2 respectively). Hospital stay was significantly reduced during the study period. There was an improved pathological response in the high dose TNF group without consequences for clinical outcome.
  
  
  CONCLUSIONS
  TM-ILP remains a very effective treatment modality for limb threatening extremity STS. Moreover, reduction of dose and the growing experience in ILP led to less local toxicity and shorter hospital stay.
authors.affiliation: Dept. Surgical Oncology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Deroose
authors.affiliation: Dept. Surgical Oncology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Grünhagen
authors.affiliation: Dept. Surgical Oncology, Radboud University Nijmegen Medical Center, The Netherlands.
authors.forename: Johannes H W
authors.initials: JH
authors.lastname: de Wilt
authors.affiliation: Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.affiliation: Dept. Surgical Oncology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands. Electronic address: c.verhoef@erasmusmc.nl.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005121:Extremities; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality; D010477:Perfusion; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan
keywords: Isolated limb perfusion; Limb salvage; Sarcoma; Tumour necrosis factor α