Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

BACKGROUND: Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated. METHODS: Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up. RESULTS: Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17–159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50–1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91–1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1–23.9 vs. median, 7.35; range, 4.8–21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0–21.4 vs. median, 10.95; range, 8.0–32.6; P < .0005). In patients with follow-up of >5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011). CONCLUSIONS: ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity.