Isolated limb perfusion in the management of patients with recurrent limb melanoma: an important but limited role.

Abstract

Isolated limb perfusion (ILP) was introduced into clinical practice in the mid-1950s, based on the same principles that had been applied to develop extracorporeal cardiopulmonary bypass a few years earlier. The concept was simple. By temporarily isolating the vasculature of a limb, high cytotoxic drug concentrations could be achieved without producing serious systemic side effects. Early studies using hyperthermic ILP with melphalan for limb melanoma produced impressive results, with overall response (OR) rates of around 80% and complete response (CR) rates for measurable limb disease of 30%– 50%.1 More recent reports indicate that CR rates exceeding 50% are now obtained in most melanoma treatment centers where ILP is undertaken.2 Even higher CR rates have been reported when tumor necrosis factor (TNF) has been used with melphalan.3 Apart from the generally unacceptable option of amputation, no other form of treatment (systemic, regional, or local) achieves response rates that are consistently as high as those able to be obtained by ILP. It provides results far superior to those able to be achieved by any form of systemic chemotherapy, for example, where OR rates exceeding 20% are uncommon and CR rates rarely exceed 1%–2%. However, despite the clearly demonstrated effectiveness of ILP for limb melanoma, it is a technique still used in only a small number of centers worldwide. The principal reason for this paradoxical situation is that, although the procedure is elegantly simple in concept, in practice it is a surgical tour-de-force – technically complex and demanding, labor intensive, time consuming, and costly. It has become clear that if ILP is to be effective and safe, meticulous attention to every aspect of the procedure is essential, with comprehensive monitoring of all parameters that might influence efficacy and outcome. These considerations have meant that the use of ILP, both for melanoma and soft tissue sarcoma, has been largely restricted to a few tertiary referral centers with appropriate academic staff and sufficient resources to undertake ILP as a clinical research endeavor. The control and monitoring of systemic drug leakage, as described in the paper by Daryanani et al.4 in this issue of Annals of Surgical Oncology, represents just one of the many technical challenges which must be overcome if ILP is to be performed with safety. Because of its complexity, cost, and potential morbidity, the objectives of ILP and the indications for its use must be very clearly understood. It was shown to have no effect whatsoever on survival in the large prospective EORTC-WHO-NAPG trial5 comparing standard surgery plus adjuvant ILP with surgery alone for patients with melanomas $1.5 mm thickness. Nor has it ever been demonstrated to influence survival when used as a therapeutic procedure in the presence of macroscopic limb disease. ILP can nevertheless generate considerable morbidity, depending upon such factors as the type and dose of chemotherapeutic agents used, adequacy of oxygenation, level of hyperthermia, perfusate flow rate, and duration of perfusion. Potential complications, including damage to blood vessels, nerves, and muscles,6 need to be considered before ILP is recommended. Recurrence or in-transit metastasis confined to a limb is reported to occur in 5%–8% of melanoma patients. Satisfactory but much simpler treatment options than ILP are often available for this small group of patients. In some cases, simple surgical excision of one or two small in-transit metastases will be all that is required. If disease is more extensive but superficial, techniques such as cryotherapy, diathermy curettage, laser treatment, radiofrequency ablation, or direct cytotoxic drug injection into tumor nodules can be effective. For larger and more deeply placed lesions, local radiotherapy can be used. Recent studies have demonstrated that electroporation therapy, in which an electric field is applied across a tumor nodule via a circular array of needle electrodes Received February 2, 2001; accepted March 21, 2001. From the Sydney Melanoma Unit, Sydney Cancer Centre, Royal Prince Alfred Hospital; and Department of Surgery, University of Sydney; Sydney, NSW, Australia. Address correspondence and reprint requests to: Professor John F. Thompson, The Sydney Melanoma Unit, Royal Prince Alfred Hospital, Missenden Road, Camperdown NSW 2050, Australia; Fax: 61-2-95506316; E-mail: john@mel.rpa.cs.nsw.gov.au. Annals of Surgical Oncology, 8(7):564–565 Published by Lippincott Williams & Wilkins © 2001 The Society of Surgical Oncology, Inc.