[Hyperthermic isolated limb perfusion with TNF-alpha and melphalan for the treatment of locally advanced soft-tissue...

Regional neoadjuvant isolated limb perfusion (ILP) with TNF-alpha and melphalan (TM-ILP) for the treatment of primarily unresectable highly malignant soft tissue sarcomas. The goal is to reduce the size and devitalize the tumor in order to convert a primarily unresectable tumor into a resectable state.

Primarily nonresectable (indication for amputation or higher-grade mutilating resection), highly malignant soft tissue sarcomas of the extremities.

Vascular occlusions, thromboses, acute infections, especially of the affected extremity.

Vascular access to the artery and vein proximal to the affected limb. Arterial and venous cannulation of the vessels supplying the limb and tumor. Connection to a heart-lung machine. Application of a tourniquet or elastic bandage proximal to the catheter tips. Nuclear medicine leak rate measurement (technetium 99m) to rule out a systemic leak. Perfusion of the limb with 1-2 mg recombinant TNF-alpha (Tasonermin/Beromun, Belpharma SA, Luxembourg) for 15 min, followed by the addition of 11-13 mg melphalan per liter of limb volume and subsequent perfusion for an additional 60 min. Washing out with 2-5 l of crystalloid solution while wrapping the limb several times with elastic Esmarch bandages. Removal of the tourniquet and catheters, reconstruction of the vessels, wound closure.

Elevate and cool the limb (especially the forearm and lower leg). Close cardiovascular and clinical monitoring for existing risk of TNF-alpha-induced Septic Inflammatory Response Syndrome (SIRS) and compartment syndrome (occurring within the first 24 h after ILP). Full weight-bearing on the limb is possible. Continue elevated positioning therapy depending on the degree of swelling. The hospital stay is approximately 1 week.

Overall treatment response to TM-ILP: 60-70%. Complete remissions observed in just under 20% of cases. Limb preservation is possible in over 80% of cases.