title: Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion.
abstract: BACKGROUND
  Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma.
  
  
  METHODS
  Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated.
  
  
  RESULTS
  Of 180 ILIs performed, 28 % (95 % confidence interval 22-35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients.
  
  
  CONCLUSIONS
  Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.
authors: Department of Immunology, Duke University, Durham, NC, USA.
authors: Gina
authors: G
authors: Shetty
authors: Georgia M
authors: GM
authors: Beasley
authors: Sara
authors: S
authors: Sparks
authors: Michael
authors: M
authors: Barfield
authors: Melanie
authors: M
authors: Masoud
authors: Paul J
authors: PJ
authors: Mosca
authors: Scott K
authors: SK
authors: Pruitt
authors: April K S
authors: AK
authors: Salama
authors: Cliburn
authors: C
authors: Chan
authors: Douglas S
authors: DS
authors: Tyler
authors: Kent J
authors: KJ
authors: Weinhold
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D010478:Chemotherapy, Cancer, Regional Perfusion; D016207:Cytokines / Q000097:blood*; D005121:Extremities; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012878:Skin Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D015996:Survival Rate
chemical_list: D016207:Cytokines; D008558:Melphalan