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Erschienen 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

verfasst von: 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

Erschienen in: Annals of Surgical Oncology | Ausgabe 6/2005

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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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Metadaten
Titel
Isolated Limb Perfusion With Tumor Necrosis Factor and Melphalan Prevents Amputation in Patients With Multiple Sarcomas in Arm or Leg
verfasst von
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
Publikationsdatum
01.06.2005
Erschienen in
Annals of Surgical Oncology / Ausgabe 6/2005
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/ASO.2005.03.059

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