Background: Recurrent melanoma of the extremity has been treated by local excision, systemic chemotherapy, amputation, or a combination of these approaches. Hyperthermic isolated limb perfusion (HILP) provides a method of limb preservation through isolation, allowing the administration of chemotherapy in higher doses than is possible through systemic treatment.
Methods: An experimental group of 59 HILP patients with melanoma recurrences of the extremity was studied prospectively. A control group of 248 melanoma patients with similar recurrences was excluded from HILP because their recurrences were in non-extremity locations. The experimental group underwent HILP and excision; the control group had excision only. The experimental procedure consisted of vascular isolation of the affected extremity and a 1-hour perfusion with melphalan. Temperatures were maintained at 40°C in the perfusion circuit.
Results: The HILP patients had a lower rate of locoregional recurrence (P=.028) and demonstrated increased survival (P=.026) compared to the control group. In multivariate regression analysis, which included age, ulceration and thickness of the primary, and the treatment variable of perfusion, age (P=.02) and perfusion for the treatment of recurrence (P=.006) were significant predictors of survival.
Conclusions: HILP improves prognosis by sterilizing the treated extremity, controlling locoregional disease, and perhaps preventing metastasis, thus having a positive impact on overall survival.
McBride CM, Sugarbaker EV, Hickey RC. Prophylactic isolation-perfusion as the primary therapy for invasive malignant melanoma of the limbs.Ann Surg 1975;182:316.PubMedGoogle Scholar
Reintgen DS, Cox C, Slingluff CL, et al. Recurrent malignant melanoma: the identification of prognostic factors to predict survival.Ann Plast Surg 1992;28:45.PubMedGoogle Scholar
Balch CM, Soong S-J, Bartolucci AA, et al. Efficacy of an elective lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger.Ann Surg 1996;224:255.CrossRefPubMedGoogle Scholar
McClay EF, Mastragelo MJ, Sprandio JD, et al. The importance of tamoxifen to a cisplatin-containing regimen in the treatment of metastatic melanoma.Cancer 1989;63:1292.PubMedGoogle Scholar
Creech OJ, Krementz ET, Ryan RF, Winblad JN. Chemotherapy of cancer. Regional perfusion using an extracorporeal circuit.Am Surg 1958;148:616.Google Scholar
Krementz ET, Ryan RF. Chemotherapy of melanoma of the extremity by perfusion. Fourteen year clinical experience.Ann Surg 1972;175:900.PubMedGoogle Scholar
Reintgen DS, Cruse CW, Wells KE, Saba HI, Slingluff CL Jr. Isolated limb perfusion for recurrent melanoma of the extremity.Ann Plast Surg 1992;28:50.PubMedGoogle Scholar
Stehlin JS. Hyperthermic perfusion with chemotherapy for cancer of the extremity.Surg Gynecol Obstet 1969;129:305.PubMedGoogle Scholar
Olszewski WL, Grzelak I, Ziolkowaska A, Engeset A. Effect of local hyperthermia on lymph immune cells and lymphokines of normal human skin.J Surg Oncol 1989;41:109.PubMedGoogle Scholar
Van Ginkel RJ, Hoekstra HJ, Eggermont AMM, et al. Isolated limb perfusion of an irradiated foot with tumor necrosis factor, interferon, and melphalan.Arch Surg 1996;131:672.PubMedGoogle Scholar
Edwards MS, Soong SJ, Boddie AN, et al. Isolated limb perfusion for localized melanoma of the extremity.Arch Surg 1990;128:317.Google Scholar
Fraker DL, Alexander HR, Andrich M, Rosenburg S. Treatment of patients with melanoma of the extremity using hyperthermic isolated limb perfusion with melphalan, tumor necrosis factor and interferon-gamma: Results of a tumor necrosis factor dose-escalation study.JCO 1996;14:479.Google Scholar
Cohen MH, Ketcham AS, Felix EL, et al. Prognostic factors in patients undergoing lymphadenectomy for malignant melanoma.Ann Surg 1977;186:635.PubMedGoogle Scholar
Wong JH, Wanek L, Chang LC, et al. The importance of anatomic site in prognosis with cutaneous melanoma.Arch Surg 1991;126:486.PubMedGoogle Scholar
Karakousis CP, Temple DF, Moore R, Ambrus L. Prognostic parameters in recurrent malignant melanoma.Cancer 1983;52:575.PubMedGoogle Scholar
Shaw HM, Beattie CW, McCarrthy WH, Milton GW. Late relapse from cutaneous stage I malignant melanoma.Surg 1985;120:1155.Google Scholar
Shaw HM, Balch CM, Soong SJ, Milton GW, McCarthy WH. Prognostic histopathological factors in malignant melanoma.Pathology 1986;17:271.Google Scholar
Markowitz JS, Cosini LA, Carey RW, et al. Prognosis after initial recurrence of cutaneous melanoma.Arch Surg 1991;126:703.PubMedGoogle Scholar
Klein ES, Den-Ari GY. Isolation perfusion with cisplatin for malignant melanoma of the limbs.Cancer 1987;59:1068.PubMedGoogle Scholar
Van der Hoop RG, Vecht CJ, van der Burg ME, et al. Prevention of cisplatin neurotoxicity with an ACTH (4–9) analogue in patients with ovarian cancer.N Engl J Med 1990;322:89.PubMedGoogle Scholar
Lienard D, Ewalenko P, Delmotte JJ, et al. High dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanomas and sarcomas.JCO 1992;1:5260.Google Scholar
Fenn NJ, Horgan K, Johnson RC, Hughes LE, Mansel RE. A randomized controlled trial of prophylactic isolated cytotoxic perfusion for poor-prognosis primary melanoma of the lower limb.Eur J Surg Oncol 1997;23(1):6.CrossRefPubMedGoogle Scholar
Ross M. Results of randomized surgical trials for melanoma. 6th World Congress on Cancers of the Skin. Buenos Aires, Argentina, 1995. Abstract.Google Scholar
Klop WMC, Vrouenraets BC, van Geel BN, et al. Repeat isolated limb perfusion with melphalan for recurrent melanoma of the limbs.J Am Coll Surg 1996;182:467.PubMedGoogle Scholar
Gutman M, Abu-Abid S, Inbar M, et al. Intra-arterial chemotherapy with concomitant hemofiltration (chemofiltration) for treatment of loco-regional or pelvic metastases from malignant melanoma.Melanoma Research 1996;6:167.PubMedGoogle Scholar
Thompson J.Vascular isolation techniques for regional chemotherapy. Sydney: University of Sydney; 1996. Thesis.Google Scholar