Long-term results of tumor necrosis factor alpha- and melphalan-based isolated limb perfusion in locally advanced extremity soft tissue sarcomas

J Clin Oncol. 2011 Oct 20;29(30):4036-44. doi: 10.1200/JCO.2011.35.6618. Epub 2011 Sep 19.

Abstract

Purpose: 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.

Patients and 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%.

Conclusion: 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Chemotherapy, Cancer, Regional Perfusion / adverse effects
  • Chemotherapy, Cancer, Regional Perfusion / methods*
  • Child
  • Combined Modality Therapy
  • Disease-Free Survival
  • Extremities
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperthermia, Induced
  • Male
  • Melphalan / administration & dosage
  • Melphalan / adverse effects
  • Middle Aged
  • Recombinant Proteins / administration & dosage
  • Sarcoma / drug therapy*
  • Soft Tissue Neoplasms / drug therapy*
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / adverse effects
  • Young Adult

Substances

  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Melphalan