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

Abstract

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 yearsÕ 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 yearsÕ 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.

TNF dose reduction and shortening of duration of isolated limb perfusion for locally advanced soft tissue sarcoma of the extremities is safe and effective in terms of long‐term patient outcome

“…The long-term limb salvage rate in group C (median followup 32 months) is 85.2% which is similar to other series with a com- parable or shorter median follow-up [36][37][38]. We know, however, from our own experience that ILP followed by resection and external beam radiotherapy can lead to major late vascular morbidity requiring amputation, even after more than 10 years [39,40]. It is thus to be expected that this limb salvage rate will further drop in the future, but until now no other series with such a long follow-up time have been published.…”

Dermatofibrosarcoma protuberans: Recurrence is related to the adequacy of surgical margins

“…[12] After six weeks the tumor had successfully reduced in volume and a radical resection was performed. The wound was closed with a split skin graft.…”

“…The patient who underwent a radical resection after a HILP treatment was treated with adjuvant radiotherapy as well, according to the institutional perfusion protocol. [12] Patient 6 in Tabel 2 was referred after repeated recurrences that were treated surgically elsewhere. We were able to resect the recurrence marginally and adjuvant radiotherapy was administered.…”

Isolierte Extremitätenperfusion mit TNFα und Zytostatika: eine Revolution in der Behandlung lokal fortgeschrittener Weichgewebssarkome der Extremitäten

“…Overall response rates ranging from 53% to 94% and limb salvage rates from 58% to 90% were reported, although it should be noted that a variety of definitions for the terms locally advanced, complete, partial, and overall response was used by the different authors [50,109,116,118,119,[129][130][131][132][133][134]. Gradually, TNF-based ILP was activated and performed in 36 centers throughout Europe; however, fewer than 10 centers have long-lasting experience with the technique [51].…”