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Plasma Cytokine Analysis in Patients with Advanced Extremity Melanoma Undergoing Isolated Limb Infusion

  • Regional Cancer Therapies
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

Supported in part by T32 Grant CA093245-10 from NIH (G.M.B.) and Duke Translational Research Institute CTSA Grant (UL1RR024128). The ADH-1 trial was supported by a grant from Adherex Technologies, Inc. Bayer Healthcare Pharmaceuticals provided study drug (sorafenib, Nexavar) for the phase I trial of systemic sorafenib and regional melphalan. D.S.T. is on the speaker’s bureau of Novartis, has been a Scientific Advisory Board Member for Roche/Genetech, and has received clinical trial support from Merck/ScheringPlough Corporation.

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Authors and Affiliations

  1. Department of Immunology, Duke University, Durham, NC, USA

    Gina Shetty BS, Melanie Masoud BS & Kent J. Weinhold PhD

  2. Department of Surgery, Duke University, Durham, NC, USA

    Georgia M. Beasley MD, Sara Sparks BS, MT, ASCP, Michael Barfield MD, Paul J. Mosca MD, PhD, Scott K. Pruitt MD, PhD, Douglas S. Tyler MD & Kent J. Weinhold PhD

  3. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA

    Cliburn Chan MD, PhD

  4. Department of Medicine, Duke University, Durham, NC, USA

    April K. S. Salama MD

Authors
  1. Gina Shetty BS
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  2. Georgia M. Beasley MD
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  3. Sara Sparks BS, MT, ASCP
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  4. Michael Barfield MD
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  5. Melanie Masoud BS
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  6. Paul J. Mosca MD, PhD
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  7. Scott K. Pruitt MD, PhD
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  9. Cliburn Chan MD, PhD
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Corresponding author

Correspondence to Georgia M. Beasley MD.

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The first two authors contributed equally to this work, and both should be considered first author.

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Shetty, G., Beasley, G.M., Sparks, S. et al. Plasma Cytokine Analysis in Patients with Advanced Extremity Melanoma Undergoing Isolated Limb Infusion. Ann Surg Oncol 20, 1128–1135 (2013). https://doi.org/10.1245/s10434-012-2785-5

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  • DOI: https://doi.org/10.1245/s10434-012-2785-5

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