title: Isolated limb perfusion for in-transit melanoma metastases: melphalan or TNF-melphalan perfusion?
abstract: Indications for treatment of melanoma in-transit metastases (ITMs) confined to the limb with isolated limb perfusion (ILP) are not well defined. This study reports the Groningen regional therapeutic perfusion experience with melphalan (M-ILP) and TNF-melphalan (TM-ILP) for ITMs, and reviews of the melanoma TNF-melphalan ILP literature. Between 1991 and 2012, 60 patients were treated with ILP. Patients with "small" ITMs received M-ILP (10-13 mg melphalan/L limb volume) and patients with "bulky" disease TM-ILP (1-4 mg TNF); 19 M-ILPs and 41 TM-ILPs were performed, 26 Stage IIIB, 31 Stage IIIB and 1 stage IV disease. Overall response after 57 ILPs was 90%; CR 27 (45%), PR 27 (45%), no response 3 (5%); after 9 M-ILPs CR 6 (32%) and 41 TM-ILPs CR 21 (51%, P = 0.124). For younger patients (<65 years) CR was 69% and for elderly patients 29% (P = 0.003). For low volume disease (<5 ITMs) CR was 75% and for high volume disease (≥5 ITMs) 41% (P = 0.038). After median follow-up of 15 months (range, 1-144) there was local recurrence or disease progression in 36 patients (60%). Positive lymph node status was associated with local progression, absence of CR and Stage IIIC disease; these were independent prognostic factors for progression to systemic disease. M-ILP is an effective regional treatment for melanoma ITMs, whereas for bulky disease TM-ILP should be the first choice. In-field progression-free survival after ILP is determined by the biological behavior of the ITMs and the patient's immune system.
authors.affiliation: Department of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Harald J
authors.initials: HJ
authors.lastname: Hoekstra
authors.forename: Kelly
authors.initials: K
authors.lastname: Veerman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van Ginkel
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D006801:Humans; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008558:Melphalan / Q000008:administration & dosage*; D009362:Neoplasm Metastasis; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan
keywords: TNFα; in-transit metastases; melanoma; melphalan; perfusion; regional chemotherapy