title: Long-term results of tumor necrosis factor alpha- and melphalan-based isolated limb perfusion in locally advanced extremity soft tissue sarcomas.
abstract: OBJECTIVE
  Because there is no survival benefit of amputation for extremity soft tissue sarcomas (STSs), limb-sparing surgery has become the gold standard. Tumor size reduction by induction therapy to render nonresectable tumors resectable or facilitate function-preserving surgery can be achieved by tumor necrosis factor α (TNF) -based and melphalan-based isolated limb perfusion (TM-ILP). This study reports the long-term results of 231 TM-ILPs for locally advanced extremity STS.
  
  
  METHODS
  We analyzed 231 TM-ILPs in 208 consecutive patients (1991 to 2005), who were all candidates for functional or anatomic amputation for locally advanced extremity STS. All patients had a potential follow-up of up to 5 years. TM-ILP was performed under mild hyperthermic conditions with 1 to 4 mg of TNF and 10 to 13 mg/L of limb-volume melphalan. Almost all patients (85%) had intermediate- or high-grade tumors.
  
  
  RESULTS
  The overall response rate (ORR) was 71% (complete response, 18%; partial response, 53%). Multifocal sarcomas had a significantly better ORR of 83% (P = .008). The local recurrence rate was 30% (n = 70); local recurrence rates were highest for multifocal tumors (54%; P = .001) and after previous radiotherapy (54%; P < .001). Five-year overall survival rate was 42%. Survival was poorest in patients with large tumors (P = .01) and with leiomyosarcomas (P < .001). Limb salvage rate was 81%.
  
  
  CONCLUSIONS
  We demonstrated that TM-ILP results in a limb salvage rate of 81% in patients with locally advanced extremity STS who would otherwise have undergone amputation. Whenever an amputation is deemed necessary to obtain local control of an extremity STS, TM-ILP should be considered.
authors.affiliation: Daniel den Hoed Cancer Center, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Deroose
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Albertus N
authors.initials: AN
authors.lastname: van Geel
authors.forename: Jacobus W A
authors.initials: JW
authors.lastname: Burger
authors.forename: Michael A
authors.initials: MA
authors.lastname: den Bakker
authors.forename: Johannes H W
authors.initials: JH
authors.lastname: de Wilt
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects / Q000379:methods*; D002648:Child; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005121:Extremities; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan