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Isolated Limb Perfusion with Tumor Necrosis Factor Alpha and Melphalan for Locally Advanced Soft Tissue Sarcoma: Three Time Periods at Risk for Amputation

¹ Division of Surgical Oncology, Department of Surgery, University Medical Center Groningen and University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
² Department of Radiotherapy, University Medical Center Groningen and University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
³ Department of Medical Oncology, University Medical Center Groningen and University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
⁴ Department Pathology, University Medical Center Groningen and University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands

Correspondence: Address correspondence and reprint requests to: Harald J. Hoekstra, MD, PhD; E-mail: h.j.hoekstra{at}chir.umcg.nl

Background: The aim of this study was to investigate the long-term limb salvage rate and overall survival after isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma (STS).

Methods: From 1991 to 2003, 73 patients (36 men, 37 women, median age 54 [range 14–80] years) with biopsy-proven STS underwent 77 perfusions followed by delayed surgical resection, with or without adjuvant radiation. Limb salvage and overall survival curves were calculated by the Kaplan-Meier method.

Results: A total of 21 amputations (28%) were performed. Overall 1, 5, and 10 years’ limb salvage was 80.1% ± 4.8%, 68.2% ± 6.5%, and 60.6% ± 9.2%, respectively. We found that the risk of amputation was linked to three time periods. The first was within a year after perfusion, mainly as a result of massive necrosis of the tumor and overlying skin, resulting in soft tissue deficit or recurrent disease (n = 17). The second was within 5 years, with two amputations performed for late local recurrence. The third occurred 10 years after perfusion, with two amputations performed for critical leg ischemia. Another two patients developed a pathological fracture of the femur due to radiation osteonecrosis. These four patients received adjuvant radiotherapy. Overall, 1, 5, and 10 years’ survival was 82.9% ± 9.2%, 58.7% ± 13.1%, and 42.5% ± 18.2%, respectively.

Conclusions: ILP treatment with tumor necrosis factor alpha and melphalan followed by delayed surgical resection and adjuvant radiation treatment is an effective limb salvage treatment regimen for locally advanced STS. However, we observed late morbidity, with two amputations performed for critical leg ischemia and two pathological fractures of the femur in patients receiving adjuvant radiotherapy.

Key Words: Isolated limb perfusion • Sarcoma • Tumor necrosis factor alpha • Melphalan • Radiotherapy • Amputation • Late morbidity

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