Isolated Limb Perfusion and Infusion for Extremity Soft Tissue Sarcoma: A Contemporary Systematic Review and Meta-Analysis

Isolated limb perfusion (ILP) and isolated limb infusion (ILI) have been variably used in recent years for the treatment of locally advanced or marginally resectable extremity soft tissue sarcomas (STSs). We performed a systematic review and meta-analysis of contemporary studies to further characterize treatment patterns and outcomes. PubMed was queried for articles published in or after the year 2000, in the English language, with > 10 patients, and with adequate outcome data following ILP/ILI. Descriptive aggregate statistics were performed. Nineteen studies that met the inclusion criteria were identified, with a total of 1288 patients. Weighted mean patient age was 55.9 years and 52% were male. The majority underwent ILP (88%) versus 12% for ILI, and chemotherapeutic regimens used were as follows: (1) melphalan with tumor necrosis factor (TNF)-alpha (78%), (2) melphalan +/- actinomycin (10%), and (3) other regimens (12%). Most common histologies treated were malignant fibrous histiocytoma (21%), liposarcoma (16%), synovial (11%) and leiomyosarcoma (7%). Aggregate overall response rate (ORR) post-procedure was 73.3%, with 25.8% demonstrating a complete response (CR). Similar unadjusted ORRs were noted in the melphalan treatment groups with and without TNF alpha (72.0 and 67.0%, respectively; p = 0.27). Grade III toxicity was observed in 15.4% of patients, and grade IV/V toxicity was observed in 6.0% of patients. Overall limb salvage rate was 73.8% and median time to local (in-field) progression ranged from 4 to 28 months (weighted median 22.1 months). ILP and ILI for extremity STS can be safely performed with appreciable response rates and significant limb salvage rates. Further study is needed to identify optimal treatment regimens by histology.