Limb Preservation With Isolated Limb Infusion for Locally Advanced Nonmelanoma Cutaneous and Soft-Tissue Malignant Neoplasms | Clinical Pharmacy and Pharmacology | JAMA Surgery | JAMA Network
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1.
Schraffordt Koops H, Eggermont AM, Liénard D,  et al.  Hyperthermic isolated limb perfusion for the treatment of soft tissue sarcomas.  Semin Surg Oncol. 1998;14(3):210-2149548603PubMedGoogle ScholarCrossref
2.
Rööser B, Gustafson P, Rydholm A. Is there no influence of local control on the rate of metastases in high-grade soft tissue sarcoma?  Cancer. 1990;65(8):1727-17292317756PubMedGoogle ScholarCrossref
3.
Williard WC, Hajdu SI, Casper ES, Brennan MF. Comparison of amputation with limb-sparing operations for adult soft tissue sarcoma of the extremity.  Ann Surg. 1992;215(3):269-2751543400PubMedGoogle ScholarCrossref
4.
Stotter A. Comparison of amputation with limb-sparing operations for adult soft tissue sarcoma of the extremity.  Ann Surg. 1992;216(5):615-6161444656PubMedGoogle Scholar
5.
Gustafson P, Rööser B, Rydholm A. Is local recurrence of minor importance for metastases in soft tissue sarcoma?  Cancer. 1991;67(8):2083-20862004326PubMedGoogle ScholarCrossref
6.
Rosenberg SA, Tepper J, Glatstein E,  et al.  The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy.  Ann Surg. 1982;196(3):305-3157114936PubMedGoogle ScholarCrossref
7.
Yang JC, Chang AE, Baker AR,  et al.  Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity.  J Clin Oncol. 1998;16(1):197-2039440743PubMedGoogle Scholar
8.
O’Sullivan B, Davis AM, Turcotte R,  et al.  Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial.  Lancet. 2002;359(9325):2235-224112103287PubMedGoogle ScholarCrossref
9.
Verhoef C, de Wilt JH, Grünhagen DJ, van Geel AN, ten Hagen TL, Eggermont AM. Isolated limb perfusion with melphalan and TNF-α in the treatment of extremity sarcoma.  Curr Treat Options Oncol. 2007;8(6):417-42718066703PubMedGoogle ScholarCrossref
10.
Grunhagen DJ, de Wilt JH, Graveland WJ, van Geel AN, Eggermont AM. The palliative value of tumor necrosis factor α-based isolated limb perfusion in patients with metastatic sarcoma and melanoma.  Cancer. 2006;106(1):156-16216323177PubMedGoogle ScholarCrossref
11.
Thompson JF, Kam PC, Waugh RC, Harman CR. Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion.  Semin Surg Oncol. 1998;14(3):238-2479548607PubMedGoogle ScholarCrossref
12.
Moncrieff MD, Kroon HM, Kam PC, Stalley PD, Scolyer RA, Thompson JF. Isolated limb infusion for advanced soft tissue sarcoma of the extremity.  Ann Surg Oncol. 2008;15(10):2749-275618648882PubMedGoogle ScholarCrossref
13.
Hegazy MA, Kotb SZ, Sakr H,  et al.  Preoperative isolated limb infusion of doxorubicin and external irradiation for limb-threatening soft tissue sarcomas.  Ann Surg Oncol. 2007;14(2):568-57617094027PubMedGoogle ScholarCrossref
14.
Möller MG, Lewis JM, Dessureault S, Zager JS. Toxicities associated with hyperthermic isolated limb perfusion and isolated limb infusion in the treatment of melanoma and sarcoma.  Int J Hyperthermia. 2008;24(3):275-28918393005PubMedGoogle ScholarCrossref
15.
Beasley GM, Petersen RP, Yoo J,  et al.  Isolated limb infusion for in-transit malignant melanoma of the extremity: a well-tolerated but less effective alternative to hyperthermic isolated limb perfusion.  Ann Surg Oncol. 2008;15(8):2195-220518528730PubMedGoogle ScholarCrossref
16.
Lindnér P, Doubrovsky A, Kam PC, Thompson JF. Prognostic factors after isolated limb infusion with cytotoxic agents for melanoma.  Ann Surg Oncol. 2002;9(2):127-13611888868PubMedGoogle Scholar
17.
Beasley GM, Caudle A, Petersen RP,  et al.  A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US.  J Am Coll Surg. 2009;208(5):706-71719476821PubMedGoogle ScholarCrossref
18.
Wieberdink J, Benckhuysen C, Braat RP, van Slooten EA, Olthuis GA. Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions.  Eur J Cancer Clin Oncol. 1982;18(10):905-9106891640PubMedGoogle ScholarCrossref
19.
Gehan EA, Tefft MC. Will there be resistance to the RECIST (Response Evaluation Criteria in Solid Tumors)?  J Natl Cancer Inst. 2000;92(3):179-18110655425PubMedGoogle ScholarCrossref
20.
Hoekstra HJ. Extremity perfusion for sarcoma.  Surg Oncol Clin N Am. 2008;17(4):805-824, ix18722920PubMedGoogle ScholarCrossref
21.
Lejeune FJ, Pujol N, Liénard D,  et al.  Limb salvage by neoadjuvant isolated perfusion with TNF-α and melphalan for non-resectable soft tissue sarcoma of the extremities.  Eur J Surg Oncol. 2000;26(7):669-67811078614PubMedGoogle ScholarCrossref
22.
Rossi CR, Vecchiato A, Foletto M,  et al.  Phase II study on neoadjuvant hyperthermic-antiblastic perfusion with doxorubicin in patients with intermediate or high grade limb sarcomas.  Cancer. 1994;73(8):2140-21468156518PubMedGoogle ScholarCrossref
23.
Thompson JF, Kam PC. Current status of isolated limb infusion with mild hyperthermia for melanoma.  Int J Hyperthermia. 2008;24(3):219-22518393000PubMedGoogle ScholarCrossref
24.
Santillan AA, Delman KA, Beasley GM,  et al.  Predictive factors of regional toxicity and serum creatine phosphokinase levels after isolated limb infusion for melanoma: a multi-institutional analysis.  Ann Surg Oncol. 2009;16(9):2570-257819543771PubMedGoogle ScholarCrossref
25.
Klaase JM, Kroon BB, Benckhuijsen C, van Geel AN, Albus-Lutter CE, Wieberdink J. Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities.  Cancer. 1989;64(3):616-6212743257PubMedGoogle ScholarCrossref
26.
Feig BW, Ross MI, Hunt KK,  et al.  A prospective evaluation of isolated limb perfusion with doxorubicin in patients with unresectable extremity sarcomas.  Ann Surg Oncol. 2004;11(2):S80-S80Google ScholarCrossref
27.
Olieman AF, Liénard D, Eggermont AM,  et al.  Hyperthermic isolated limb perfusion with tumor necrosis factor α, interferon gamma, and melphalan for locally advanced nonmelanoma skin tumors of the extremities: a multicenter study.  Arch Surg. 1999;134(3):303-30710088573PubMedGoogle ScholarCrossref
28.
Eggermont AM, Schraffordt Koops H, Klausner JM,  et al.  Isolated 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 experience.  Ann Surg. 1996;224(6):756-7658968230PubMedGoogle ScholarCrossref
29.
Eggermont AM, Schraffordt Koops H, Liénard D,  et al.  Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial.  J Clin Oncol. 1996;14(10):2653-26658874324PubMedGoogle Scholar
30.
Cornett WR, McCall LM, Petersen RP,  et al; American College of Surgeons Oncology Group Trial Z0020.  Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.  J Clin Oncol. 2006;24(25):4196-420116943537PubMedGoogle ScholarCrossref
Original Article
July 2011

Limb Preservation With Isolated Limb Infusion for Locally Advanced Nonmelanoma Cutaneous and Soft-Tissue Malignant Neoplasms

Author Affiliations

Author Affiliations: Division of Surgical Oncology, Medical College of Wisconsin Clinical Cancer Center, Milwaukee (Dr Turaga); Duke University, Durham, North Carolina (Drs Beasley and Tyler); Roswell Park Cancer Institute, Buffalo, New York (Dr Kane); Emory University, Atlanta, Georgia (Dr Delman); Department of Surgery, University of Florida, Gainesville (Dr Grobmyer); Departments of Cutaneous Oncology (Drs Gonzalez and Zager) and Sarcoma Oncology (Drs Gonzalez, Letson, Cheong, and Zager), Moffitt Cancer Center, Tampa, Florida; and Department of Surgery, University of South Florida, Tampa (Drs Gonzalez, Letson, Cheong, and Zager).

Arch Surg. 2011;146(7):870-875. doi:10.1001/archsurg.2011.139
Abstract

Objective To demonstrate the efficacy of isolated limb infusion (ILI) in limb preservation for patients with locally advanced soft-tissue sarcomas and nonmelanoma cutaneous malignant neoplasms.

Background Locally advanced nonmelanoma cutaneous and soft-tissue malignant neoplasms, including soft-tissue sarcomas of the extremities, can pose significant treatment challenges. We report our experience, including responses and limb preservation rates, using ILI in cutaneous and soft-tissue malignant neoplasms.

Methods We identified 22 patients with cutaneous and soft-tissue malignant neoplasms who underwent 26 ILIs with melphalan and dactinomycin from January 1, 2004, through December 31, 2009, from 5 institutions. Outcome measures included limb preservation and in-field response rates. Regional toxic effects were measured using the Wieberdink scale and serum creatinine phosphokinase levels.

Results The median age was 70 years (range, 19-92 years), and 12 patients (55%) were women. Fourteen patients (64%) had sarcomas, 7 (32%) had Merkel cell carcinoma, and 1 (5%) had squamous cell carcinoma. The median length of stay was 5.5 days (interquartile range, 4-8 days). Twenty-five of the 26 ILIs (96%) resulted in Wieberdink grade III or less toxicity, and 1 patient (4%) developed grade IV toxicity. The median serum creatinine phosphokinase level was 127 U/L for upper extremity ILIs and 93 U/L for lower extremity ILIs. Nineteen of 22 patients (86%) underwent successful limb preservation. The 3-month in-field response rate was 79% (21% complete and 58% partial), and the median follow-up was 8.6 months (range, 1-63 months). Five patients underwent resection of disease after an ILI, of whom 80% are disease free at a median of 8.6 months.

Conclusions Isolated limb infusion provides an attractive alternative therapy for regional disease control and limb preservation in patients with limb-threatening cutaneous and soft-tissue malignant neoplasms. Short-term response rates appear encouraging, yet durability of response is unknown.

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