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

Objective The objective of the study was to achieve limb salvage in pa tients with locally advanced soft tissue sarcomas that can only be tre ated by amputation or functionally mutilating surgery by performing an isolated limb perfusion (ILP) with tumor necrosis factor (TNF) + melp halan (M) as induction biochemotherapy to obtain local control and mak e limb-sparing surgery possible. Summary Background Data To increase t he number of limb-sparing resections in the treatment of locally advan ced extremity soft tissue sarcoma, preoperative radiation therapy or c hemotherapy or a combination of the two often are applied. The ILP wit h cytostatic agents alone is another option but rarely is used because of rather poor results. The efficacy of the application of TNF in ILP markedly has changed this situation. Methods In 8 cancer centers, 186 patients were treated over a period oi almost 4.5 years. There were 1 07 (57%) primary and 79 (43%) recurrent sarcomas, mostly high grade (1 10 grade III; 51 grade II; and 25 very large, recurrent, or multiple g rade I sarcomas). The composition of this series of patients is unusua l: 42 patients (23%) had multifocal primary or multiple recurrent tumo rs; median tumor size was very large (16 cm); 25 patients (13%) had kn own systemic metastases at the time of the ILP. Patients underwent a 9 0-minute ILP at 39 to 40 C with TNF + melphalan. The first 55 patients also received interieron-tau. A delayed marginal resection of the tum or remnant was done 2 to 4 months after ILP. Results A major tumor res ponse was seen in 82% of the patients rendering these large sarcomas r esectable in most cases. Clinical response rates were: 33 complete res ponse (CR) (18%), 106 partial response (PR) (57%), 42 no change (NC) ( 22%), and 5 progressive disease (PD) (3%). Final outcome was defined b y clinical and pathologic response: 54 CR (29%), 99 PR (53%), 29 NC (1 6%), and 4 PD (2%). At a median follow-up of almost 2 years (22 months ; range, 6-58 months), limb salvage was achieved in 82%. Regional toxi city was limited and systemic toxicity minimal to moderate, easily man aged, with no toxic deaths. Conclusions In the setting of isolated lim b perfusion, TNF is an active anticancer drug in patients. The ILP wit h TNF + melphalan can be performed safely in many centers and is an ef fective induction treatment with a high response rate that can achieve limb salvage in patients with locally advanced extremity soft tissue sarcoma.