title: Factors affecting survival after complete response to isolated limb perfusion in patients with in-transit melanoma.
abstract: BACKGROUND
  Isolated limb perfusion (ILP) results in complete response (CR) rates of 60% to 90% in patients with regionally advanced melanoma. Survival after a CR may be influenced by various factors, particularly out-of-field disease in iliac lymph nodes (ILN) identified during lower-extremity ILP. We examined clinical and pathological parameters, including ILN status and outcome, for patients with in-transit melanoma who had a CR to ILP.
  
  
  METHODS
  From May 1992 to July 1997, 50 patients (16 men and 34 women; median age, 57 years) with stage IIIA or IIIAB melanoma had a CR to a 90-minute hyperthermic iliac ILP with melphalan (10 mg/L limb volume, n = 20) or melphalan and tumor necrosis factor (4-6 mg+/-200 microg interferon; n = 30). Clinical and pathological parameters were analyzed by univariate and Cox proportional hazards models to determine which were associated with survival or in-field recurrence.
  
  
  RESULTS
  The median in-field recurrence-free survival in the cohort of 50 patients after a CR to ILP was 1.4 years, and the actuarial 5-year in-field recurrence-free survival was 30%. By univariate analysis, there was a trend for improved outcome with female sex and stage IIIA (vs. IIIAB) at initial diagnosis was associated with improved survival after a CR to ILP (P = .056 and .012, respectively). Eleven (22%) of 50 patients had positive ILNs identified and resected at ILP. The probability of overall in-field recurrence was 70% after 4 years, and there was no difference between those with or without positive ILNs; median time to in-field recurrence was 13 and 19 months, respectively (P = .62). Similarly, overall survival was not influenced by positive ILN status (median [months]: +ILN, 69 vs. -ILN, 58; P = .68). Of note, Cox models identified that the risk of death was significantly greater in those with a history of prior systemic therapy (hazard ratio: 2.67 [95% confidence interval, 1.17-6.11]; P = .02) and those with an in-transit lesion size > or =1.4 cm2 (hazard ratio, 3.12 [95% confidence interval, 1.30-7.5]; P = .011). When these two variables were combined, there was a highly significant association with shortened survival (P = .002 by log-rank test).
  
  
  CONCLUSIONS
  These data indicate that for patients undergoing ILP and in whom positive ILNs are found and resected, ILP is justified. In addition, patients who have a CR after ILP and have a history of prior treatment or larger lesions should be considered for adjuvant systemic therapy.
authors.affiliation: Surgery Branch and the Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Zogakis
authors.forename: D L
authors.initials: DL
authors.lastname: Bartlett
authors.forename: S K
authors.initials: SK
authors.lastname: Libutti
authors.forename: D J
authors.initials: DJ
authors.lastname: Liewehr
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: D L
authors.initials: DL
authors.lastname: Fraker
authors.forename: H R
authors.initials: HR
authors.lastname: Alexander
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods; D018572:Disease-Free Survival; D005121:Extremities / Q000098:blood supply; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D007372:Interferons / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007372:Interferons; D008558:Melphalan