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

• Published in: Journal of clinical oncology Vol. 29; no. 30; pp. 4036 - 4044
• Main Authors: DEROOSE, Jan P, EGGERMONT, Alexander M. M, VAN GEEL, Albertus N, BURGER, Jacobus W. A, DEN BAKKER, Michael A, DE WILT, Johannes H. W, VERHOEF, Cornelis
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.10.2011
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Chemotherapy, Cancer, Regional Perfusion - adverse effects; Chemotherapy, Cancer, Regional Perfusion - methods; Child; Combined Modality Therapy; Dermatology; Disease-Free Survival; Extremities; Female; Follow-Up Studies; Humans; Hyperthermia, Induced; Male; Medical sciences; Melphalan - administration & dosage; Melphalan - adverse effects; Middle Aged; Recombinant Proteins - administration & dosage; Sarcoma - drug therapy; Soft Tissue Neoplasms - drug therapy; Tumor Necrosis Factor-alpha - administration & dosage; Tumor Necrosis Factor-alpha - adverse effects; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Young Adult; Antineoplastic agent; Cytokine; Soft tissue sarcoma; Malignant tumor; Long term; Isolated limb perfusion; Alkylating agent; Cancerology; Nitrogen mustard; Limb; Melphalan; Locally advanced stage; Tumor necrosis factor α; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2011.35.6618

Because 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. We 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. The 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%. We 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.