Long-term outcome of hyperthermic isolated limb perfusion (HILP) in the treatment of locoregionally metastasised malignant melanoma of the extremities

Objective: The aim is to analyse a modified standardised HILP procedure regarding the response rates, local recurrences and complication rates. Patients and methods: 152 patients (101 females, 51 males) with an average age of 62 years and locoregionally metastasised malignant melanoma underwent HILP using melphalan and dactinomycin between 1992 and 2007. Using M.D. Anderson's classification at the time of the perfusion 51 patients presented in stage IIIA, 43 patients in stage IIIAB and 58 patients in stage IV. If indicated, lymph node dissection was performed simultaneously just before perfusion of the extremity. Results: Complete remission was observed in 91 (62.7%) of 145 patients, partial remission in 26 (17.9%) patients. 28 (19.3%) patients showed no response. The overall response rate was 80.7% (117 of 145 patients). Severe complications (Wieberdink IV/V) were seen in eight cases. The average recurrence-free survival was 17 months. The median survival was 39 months; the five-year overall survival rate was 38%. The overall survival rate was significantly influenced by the stage of the disease. Conclusion: HILP is an efficient therapy for multiple or recurrent in-transit metastases of malignant melanoma of the lower extremities. The efficiency increased by improving the technique of the perfusion. Long-term survival can be observed in patients without regional lymph node metastases or distant metastases.

[1]  P. Bechi,et al.  Toxicity and morbility after isolated lower limb perfusion in 242 chemo-hyperthermal treatments for cutaneous melanoma: The experience of the Tuscan Reference Centre , 2008, Journal of experimental & clinical cancer research : CR.

[2]  R. Petersen,et al.  Isolated Limb Infusion for In-Transit Malignant Melanoma of the Extremity: A Well-Tolerated but Less Effective Alternative to Hyperthermic Isolated Limb Perfusion , 2008, Annals of Surgical Oncology.

[3]  W. Hohenberger,et al.  Long-term functional outcome after hyperthermic isolated limb perfusion (HILP) , 2008, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[4]  Jeffrey E. Lee,et al.  Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  W. Hohenberger,et al.  Hyperthermic isolated limb perfusion (HILP) in malignant melanoma. Experience with 101 patients. , 2006, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[6]  F. Lejeune,et al.  In transit metastases of malignant melanoma treated by high dose rTNFα in combination with interferon-γ and melphalan in isolation perfusion , 1992, World Journal of Surgery.

[7]  F. Cavaliere,et al.  TNFα-Based Isolated Hyperthermic Limb Perfusion (HILP) in the Treatment of Limb Recurrent Melanoma: Update 16 Years after Its First Clinical Application , 2004, Journal of chemotherapy.

[8]  H. Teppler,et al.  Management of Complicated Appendicitis and Comparison of Outcome with Other Primary Sites of Intra-abdominal Infection: Results of a Trial Comparing Ertapenem and Piperacillin-Tazobactam , 2004, Journal of chemotherapy.

[9]  S. Mocellin,et al.  Isolated limb perfusion in locally advanced cutaneous melanoma. , 2002, Seminars in oncology.

[10]  W. Hohenberger,et al.  Surgical therapy for distant metastases of malignant melanoma , 2000, Cancer.

[11]  A. Eggermont,et al.  Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, a , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  W. Hohenberger,et al.  Hyperthermic Isolated Limb Perfusion – 23 Years’ Experience and Improvement of Results by Modification of Technique , 1998, Oncology Research and Treatment.

[13]  A. Eggermont,et al.  Isolated limb perfusion in primary and recurrent melanoma: indications and results. , 1998, Seminars in surgical oncology.

[14]  P. Kam,et al.  Frequency and duration of remission after isolated limb perfusion for melanoma. , 1997, Archives of surgery.

[15]  E. Krementz,et al.  Isolated hyperthermia chemotherapy perfusion for limb melanoma. , 1996, The Surgical clinics of North America.

[16]  N. Cascinelli,et al.  Treatment of primary or relapsing limb cancer by isolation perfusion with high‐dose alpha‐tumor necrosis factor, gamma‐interferon, and melphalan , 1994, Cancer.

[17]  W. Hohenberger Isolation Perfusion for Malignant Melanomas: Established Facts and Parameters to Be Clarified , 1990 .

[18]  S. Carlini,et al.  Prognostic variables in recurrent limb melanoma treated with hyperthermic antiblastic perfusion , 1989, Cancer.

[19]  E. V. van Slooten,et al.  Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions. , 1982, European journal of cancer & clinical oncology.

[20]  R. F. Ryan,et al.  Chemotherapy of Cancer: Regional Perfusion Utilizing an Extracorporeal Circuit , 1958, Annals of surgery.