Long-Term Results of Tumor Necrosis Factor α– and Melphalan-Based Isolated Limb Perfusion in Locally Advanced Extremity Soft Tissue Sarcomas

2011 ◽  
Vol 29 (30) ◽  
pp. 4036-4044 ◽  
Author(s):  
Jan P. Deroose ◽  
Alexander M.M. Eggermont ◽  
Albertus N. van Geel ◽  
Jacobus W.A. Burger ◽  
Michael A. den Bakker ◽  
...  

PurposeBecause 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 MethodsWe 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.ResultsThe 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%.ConclusionWe 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.

2006 ◽  
Vol 24 (25) ◽  
pp. 4196-4201 ◽  
Author(s):  
Wendy R. Cornett ◽  
Linda M. McCall ◽  
Rebecca P. Petersen ◽  
Merrick I. Ross ◽  
Henry A. Briele ◽  
...  

Purpose To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-α) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma. Patients and Methods Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-α during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status. Results The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-α arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-α arm, and one disease progression–related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-α arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-α arm (P = .435 and P = .890, respectively). Conclusion In locally advanced extremity melanoma treated with HILP, the addition of TNF-α to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-α plus melphalan was associated with a higher complication rate.


2019 ◽  
Vol 17 (1) ◽  
pp. 94-106 ◽  
Author(s):  
Rintaro Moroi ◽  
Katsuya Endo ◽  
Katsutoshi Yamamoto ◽  
Takeo Naito ◽  
Motoyuki Onodera ◽  
...  

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