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Kaposi sarcoma (KS) is a rare soft tissue sarcoma. In case of locally advanced disease, mutilating surgery such as amputations or major reconstructive procedures are sometimes inevitable. The aim of this study was to evaluate the effectiveness of isolated limb perfusion (ILP) in patients with locally advanced KS of the extremities. All patients who underwent ILP for KS between 1996 and 2018 at Erasmus MC, Rotterdam were identified. Clinical data was obtained from either a prospectively maintained database or retrospective assessment of patient files. A total of 14 primary ILP's were performed in 11 patients. Median follow-up from primary ILP was 30 months (range, 5–98). The overall response rate of primary ILP was 100%, with a complete response (CR) rate of 50%. Only minimal local toxicity (Wieberdink I-III) was observed. Local progressive disease occurred after eight primary ILP's (57%) with a median local progression free survival (PFS) of 18 months (95% confidence interval [CI]: 7.0–28.9). Subsequently, four (46%) patients received a total of 5 recurrent ILP's. After the recurrent ILP on the same leg, the overall response rate was 75% and a CR-rate of 50%. One patient needed amputation post-operatively resulting in a limb salvage rate of 91%. One (9%) patient developed metastases four months after ILP. ILP is a highly effective treatment modality with very limited morbidity rates for patients with locally advanced KS of the extremity. ILP should be considered as a treatment modality for locally advanced KS of the extremities. [ABSTRACT FROM AUTHOR]