Annals of Surgical Oncology

, Volume 12, Issue 6, pp 473–479 | Cite as

Isolated Limb Perfusion With Tumor Necrosis Factor and Melphalan Prevents Amputation in Patients With Multiple Sarcomas in Arm or Leg

  • Dirk J. Grünhagen
  • Flavia Brunstein
  • Wilfried J. Graveland
  • Albertus N. van Geel
  • Johannes H. W. de Wilt
  • Alexander M. M. Eggermont



Treatment for extremity soft tissue sarcoma (STS) has shifted in recent years from amputation to local wide excision combined with irradiation. For multiple sarcomas, this limb-sparing approach is often not possible. To avoid amputations, isolated limb perfusion (ILP) with tumor necrosis factor and melphalan is an attractive treatment option for patients with multiple extremity sarcomas.


We investigated a prospective database at a tertiary referral institute. From July 1991 to July 2003, out of 217 ILPs, 64 ILPs were performed for either multifocal primary sarcomas or multiple sarcoma recurrences in 53 patients. All ILPs were performed under mild hyperthermic conditions by using 1 to 4 mg of tumor necrosis factor and 10 to 13 mg/L of limb volume for leg and arm perfusions, respectively.


The overall response was 88%, with 42% complete response, 45% partial response, 11% no change, and 2% progressive disease. This response rate is significantly better than our experience in 153 locally advanced single-STS cases (88% vs. 69%). The toxicity of the procedure was mild to moderate in almost all cases; no treatment-related amputation had to be performed. The time to local recurrence was 29 months and differed significantly between multiple primary and multiple recurrent STS. The 5-year survival rate was 39%. Limb salvage was achieved in 45 (82%) of 55 treated limbs.


In a group of patients who are uniformly candidates for amputation, ILP can achieve limb salvage in approximately four out of five patients. Because this treatment option provides excellent local control, it should be considered before an amputation is planned.


Isolated limb perfusion Soft tissue sarcoma Extremity TNF 


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Copyright information

© The Society of Surgical Oncology, Inc. 2005

Authors and Affiliations

  • Dirk J. Grünhagen
    • 1
  • Flavia Brunstein
    • 1
  • Wilfried J. Graveland
    • 2
  • Albertus N. van Geel
    • 1
  • Johannes H. W. de Wilt
    • 1
  • Alexander M. M. Eggermont
    • 1
  1. 1.Department of Surgical OncologyErasmus MC-Daniel den Hoed Cancer CenterRotterdamThe Netherlands
  2. 2.Department of StatisticsErasmus MC-Daniel den Hoed Cancer CenterThe Netherlands

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