Skip to main content
Top
Published in: Annals of Surgical Oncology 6/2005

01-06-2005

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

Authors: Dirk J. Grünhagen, MD, Flavia Brunstein, MD, Wilfried J. Graveland, MSc, Albertus N. van Geel, MD, PhD, Johannes H. W. de Wilt, MD, PhD, Alexander M. M. Eggermont, MD, PhD

Published in: Annals of Surgical Oncology | Issue 6/2005

Login to get access

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
Literature
1.
go back to reference Landis, SH, Murray, T, Bolden, S, Wingo, PA 1999Cancer statistics, 1999CA Cancer J Clin49831PubMed Landis, SH, Murray, T, Bolden, S, Wingo, PA 1999Cancer statistics, 1999CA Cancer J Clin49831PubMed
2.
go back to reference Eggermont, AM, Schraffordt Koops, H, Lienard, D, et al. 1996Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trialJ Clin Oncol14265365PubMed Eggermont, AM, Schraffordt Koops, H, Lienard, D,  et al. 1996Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trialJ Clin Oncol14265365PubMed
3.
go back to reference Eggermont, AM, Schraffordt Koops, H, Klausner, JM, et al. 1996Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experienceAnn Surg22475664; discussion 764–5CrossRefPubMed Eggermont, AM, Schraffordt Koops, H, Klausner, JM,  et al. 1996Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experienceAnn Surg22475664; discussion 764–5CrossRefPubMed
4.
go back to reference Gutman, M, Inbar, M, Lev-Shlush, D, et al. 1997High dose tumor necrosis factor-alpha and melphalan administered via isolated limb perfusion for advanced limb soft tissue sarcoma results in a >90% response rate and limb preservationCancer79112937PubMed Gutman, M, Inbar, M, Lev-Shlush, D,  et al. 1997High dose tumor necrosis factor-alpha and melphalan administered via isolated limb perfusion for advanced limb soft tissue sarcoma results in a >90% response rate and limb preservationCancer79112937PubMed
5.
go back to reference Rossi, CR, Foletto, M, Di Filippo, F, et al. 1999Soft tissue limb sarcomas: Italian clinical trials with hyperthermic antiblastic perfusionCancer8617429CrossRefPubMed Rossi, CR, Foletto, M, Di Filippo, F,  et al. 1999Soft tissue limb sarcomas: Italian clinical trials with hyperthermic antiblastic perfusionCancer8617429CrossRefPubMed
6.
go back to reference Lejeune, FJ, Pujol, N, Lienard, D, et al. 2000Limb salvage by neoadjuvant isolated perfusion with TNF alpha and melphalan for non-resectable soft tissue sarcoma of the extremitiesEur J Surg Oncol2666978PubMed Lejeune, FJ, Pujol, N, Lienard, D,  et al. 2000Limb salvage by neoadjuvant isolated perfusion with TNF alpha and melphalan for non-resectable soft tissue sarcoma of the extremitiesEur J Surg Oncol2666978PubMed
7.
go back to reference Hohenberger, P, Kettelhack, C, Hermann, A, Schlag, PM 2001Functional outcome after preoperative isolated limb perfusion with rhTNF alpha/melphalan for high-grade extremity sarcomaEur J Cancer37S345CrossRef Hohenberger, P, Kettelhack, C, Hermann, A, Schlag, PM 2001Functional outcome after preoperative isolated limb perfusion with rhTNF alpha/melphalan for high-grade extremity sarcomaEur J Cancer37S345CrossRef
8.
go back to reference Noorda, EM, Vrouenraets, BC, Nieweg, OE, et al. 2003Isolated limb perfusion with tumor necrosis factor-alpha and melphalan for patients with unresectable soft tissue sarcoma of the extremitiesCancer98148390CrossRefPubMed Noorda, EM, Vrouenraets, BC, Nieweg, OE,  et al. 2003Isolated limb perfusion with tumor necrosis factor-alpha and melphalan for patients with unresectable soft tissue sarcoma of the extremitiesCancer98148390CrossRefPubMed
9.
go back to reference Eggermont, AM, de Wilt, JH, ten Hagen, TL 2003Current uses of isolated limb perfusion in the clinic and a model system for new strategiesLancet Oncol442937CrossRefPubMed Eggermont, AM, de Wilt, JH, ten Hagen, TL 2003Current uses of isolated limb perfusion in the clinic and a model system for new strategiesLancet Oncol442937CrossRefPubMed
10.
go back to reference Ruka, W, Emrich, LJ, Driscoll, DL, Karakousis, CP 1989Clinical factors and treatment parameters affecting prognosis in adult high-grade soft tissue sarcomas: a retrospective review of 267 casesEur J Surg Oncol1541123PubMed Ruka, W, Emrich, LJ, Driscoll, DL, Karakousis, CP 1989Clinical factors and treatment parameters affecting prognosis in adult high-grade soft tissue sarcomas: a retrospective review of 267 casesEur J Surg Oncol1541123PubMed
11.
go back to reference Blair, SL, Lewis, JJ, Leung, D, et al. 1998Multifocal extremity sarcoma: an uncommon and controversial entityAnn Surg Oncol53740PubMed Blair, SL, Lewis, JJ, Leung, D,  et al. 1998Multifocal extremity sarcoma: an uncommon and controversial entityAnn Surg Oncol53740PubMed
12.
go back to reference Potter, DA, Kinsella, T, Glatstein, E, et al. 1986High-grade soft tissue sarcomas of the extremitiesCancer58190205PubMed Potter, DA, Kinsella, T, Glatstein, E,  et al. 1986High-grade soft tissue sarcomas of the extremitiesCancer58190205PubMed
13.
go back to reference Williard, WC, Hajdu, SI, Casper, ES, Brennan, MF 1992Comparison of amputation with limb-sparing operations for adult soft tissue sarcoma of the extremityAnn Surg21526975PubMedCrossRef Williard, WC, Hajdu, SI, Casper, ES, Brennan, MF 1992Comparison of amputation with limb-sparing operations for adult soft tissue sarcoma of the extremityAnn Surg21526975PubMedCrossRef
14.
go back to reference Pisters, PW, Leung, DH, Woodruff, J, et al. 1996Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremitiesJ Clin Oncol14167989PubMed Pisters, PW, Leung, DH, Woodruff, J,  et al. 1996Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremitiesJ Clin Oncol14167989PubMed
15.
go back to reference Trojani, M, Contesso, G, Coindre, JM, et al. 1984Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading systemInt J Cancer333742PubMed Trojani, M, Contesso, G, Coindre, JM,  et al. 1984Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading systemInt J Cancer333742PubMed
16.
go back to reference Rijswijk, CS, Geirnaerdt, MJ, Hogendoorn, PC, et al. 2003Dynamic contrast-enhanced MR imaging in monitoring response to isolated limb perfusion in high-grade soft tissue sarcoma: initial resultsEur Radiol13184958CrossRefPubMed Rijswijk, CS, Geirnaerdt, MJ, Hogendoorn, PC,  et al. 2003Dynamic contrast-enhanced MR imaging in monitoring response to isolated limb perfusion in high-grade soft tissue sarcoma: initial resultsEur Radiol13184958CrossRefPubMed
17.
go back to reference Vanel, D, Bonvalot, S, Guinebretiere, JM, et al. 2004MR imaging in the evaluation of isolated limb perfusion: a prospective study of 18 casesSkeletal Radiol331506CrossRefPubMed Vanel, D, Bonvalot, S, Guinebretiere, JM,  et al. 2004MR imaging in the evaluation of isolated limb perfusion: a prospective study of 18 casesSkeletal Radiol331506CrossRefPubMed
18.
go back to reference Wieberdink, J, Benckhuysen, C, Braat, RP, et al. 1982Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactionsEur J Cancer Clin Oncol1890510PubMed Wieberdink, J, Benckhuysen, C, Braat, RP,  et al. 1982Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactionsEur J Cancer Clin Oncol1890510PubMed
19.
go back to reference Krementz, ET, Carter, RD, Sutherland, CM, Hutton, I 1977Chemotherapy of sarcomas of the limbs by regional perfusionAnn Surg18555564PubMed Krementz, ET, Carter, RD, Sutherland, CM, Hutton, I 1977Chemotherapy of sarcomas of the limbs by regional perfusionAnn Surg18555564PubMed
20.
go back to reference Hoekstra, HJ, Schraffordt Koops, H, Molenaar, WM, Oldhoff, J 1987Results of isolated regional perfusion in the treatment of malignant soft tissue tumors of the extremitiesCancer6017037PubMed Hoekstra, HJ, Schraffordt Koops, H, Molenaar, WM, Oldhoff, J 1987Results of isolated regional perfusion in the treatment of malignant soft tissue tumors of the extremitiesCancer6017037PubMed
21.
go back to reference Klaase, JM, Kroon, BB, Benckhuijsen, C, et al. 1989Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremitiesCancer6461621PubMed Klaase, JM, Kroon, BB, Benckhuijsen, C,  et al. 1989Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremitiesCancer6461621PubMed
22.
go back to reference Feig, BW, Ross, MI, Hunt, KK 2004A prospective evaluation of isolated limb perfusion with doxorubicin in patients with unresectable extremity sarcomas (abstract 98)Ann Surg Oncol11S80 Feig, BW, Ross, MI, Hunt, KK 2004A prospective evaluation of isolated limb perfusion with doxorubicin in patients with unresectable extremity sarcomas (abstract 98)Ann Surg Oncol11S80
23.
go back to reference Lev-Chelouche, D, Abu-Abeid, S, Kollander, Y, et al. 1999Multifocal soft tissue sarcoma: limb salvage following hyperthermic isolated limb perfusion with high-dose tumor necrosis factor and melphalanJ Surg Oncol701859CrossRefPubMed Lev-Chelouche, D, Abu-Abeid, S, Kollander, Y,  et al. 1999Multifocal soft tissue sarcoma: limb salvage following hyperthermic isolated limb perfusion with high-dose tumor necrosis factor and melphalanJ Surg Oncol701859CrossRefPubMed
24.
go back to reference Grünhagen, DJ, Brunstein, F, Graveland, WJ, et al. 2004One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastasesAnn Surg24093947discussion 947–8CrossRefPubMed Grünhagen, DJ, Brunstein, F, Graveland, WJ,  et al. 2004One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastasesAnn Surg24093947discussion 947–8CrossRefPubMed
25.
go back to reference Lev-Chelouche, D, Abu-Abeid, S, Merimsky, O, et al. 1999Isolated limb perfusion with high-dose tumor necrosis factor alpha and melphalan for Kaposi sarcomaArch Surg13417780CrossRefPubMed Lev-Chelouche, D, Abu-Abeid, S, Merimsky, O,  et al. 1999Isolated limb perfusion with high-dose tumor necrosis factor alpha and melphalan for Kaposi sarcomaArch Surg13417780CrossRefPubMed
26.
go back to reference Lans, TE, de Wilt, JH, van Geel, AN, Eggermont, AM 2002Isolated limb perfusion with tumor necrosis factor and melphalan for nonresectable Stewart-Treves lymphangiosarcomaAnn Surg Oncol910049CrossRefPubMed Lans, TE, de Wilt, JH, van Geel, AN, Eggermont, AM 2002Isolated limb perfusion with tumor necrosis factor and melphalan for nonresectable Stewart-Treves lymphangiosarcomaAnn Surg Oncol910049CrossRefPubMed
27.
go back to reference Lewis, JJ, Boland, PJ, Leung, DH, et al. 1999The enigma of desmoid tumorsAnn Surg22986672discussion 872–3CrossRefPubMed Lewis, JJ, Boland, PJ, Leung, DH,  et al. 1999The enigma of desmoid tumorsAnn Surg22986672discussion 872–3CrossRefPubMed
28.
go back to reference Weitz, J, Antonescu, CR, Brennan, MF 2003Localized extremity soft tissue sarcoma: improved knowledge with unchanged survival over timeJ Clin Oncol21271925CrossRefPubMed Weitz, J, Antonescu, CR, Brennan, MF 2003Localized extremity soft tissue sarcoma: improved knowledge with unchanged survival over timeJ Clin Oncol21271925CrossRefPubMed
29.
go back to reference Lans TA, Grünhagen DJ, de Wilt JHW, et al. Isolated limb perfusions with TNF and melphalan for locally recurrent soft tissue sarcoma in previously irradiated limbs. Ann Surg Oncol 2005;12: in press. Lans TA, Grünhagen DJ, de Wilt JHW, et al. Isolated limb perfusions with TNF and melphalan for locally recurrent soft tissue sarcoma in previously irradiated limbs. Ann Surg Oncol 2005;12: in press.
Metadata
Title
Isolated Limb Perfusion With Tumor Necrosis Factor and Melphalan Prevents Amputation in Patients With Multiple Sarcomas in Arm or Leg
Authors
Dirk J. Grünhagen, MD
Flavia Brunstein, MD
Wilfried J. Graveland, MSc
Albertus N. van Geel, MD, PhD
Johannes H. W. de Wilt, MD, PhD
Alexander M. M. Eggermont, MD, PhD
Publication date
01-06-2005
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 6/2005
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/ASO.2005.03.059

Other articles of this Issue 6/2005

Annals of Surgical Oncology 6/2005 Go to the issue