Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion

Gina Shetty, Georgia M. Beasley, Sara Sparks, Michael Barfield, Melanie Masoud, Paul J. Mosca, Scott K. Pruitt, April K S Salama, Cliburn Chan, Douglas Tyler, Kent J. Weinhold

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1128-1135
Number of pages8
JournalAnnals of Surgical Oncology
Volume20
Issue number4
DOIs
StatePublished - Apr 2013
Externally publishedYes

Fingerprint

Melanoma
Extremities
Cytokines
Interleukin-1
Interleukin-12 Subunit p40
Macrophage Colony-Stimulating Factor
Interleukin-17
Granulocyte-Macrophage Colony-Stimulating Factor
Epidermal Growth Factor
Vascular Endothelial Growth Factor A
Immunologic Monitoring
Melphalan
Chemokines
Interleukin-6
Pharmacokinetics
Tissue Donors
Confidence Intervals
Technology
Neoplasms

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Shetty, G., Beasley, G. M., Sparks, S., Barfield, M., Masoud, M., Mosca, P. J., ... Weinhold, K. J. (2013). Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion. Annals of Surgical Oncology, 20(4), 1128-1135. https://doi.org/10.1245/s10434-012-2785-5

Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion. / Shetty, Gina; Beasley, Georgia M.; Sparks, Sara; Barfield, Michael; Masoud, Melanie; Mosca, Paul J.; Pruitt, Scott K.; Salama, April K S; Chan, Cliburn; Tyler, Douglas; Weinhold, Kent J.

In: Annals of Surgical Oncology, Vol. 20, No. 4, 04.2013, p. 1128-1135.

Research output: Contribution to journalArticle

Shetty, G, Beasley, GM, Sparks, S, Barfield, M, Masoud, M, Mosca, PJ, Pruitt, SK, Salama, AKS, Chan, C, Tyler, D & Weinhold, KJ 2013, 'Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion', Annals of Surgical Oncology, vol. 20, no. 4, pp. 1128-1135. https://doi.org/10.1245/s10434-012-2785-5
Shetty, Gina ; Beasley, Georgia M. ; Sparks, Sara ; Barfield, Michael ; Masoud, Melanie ; Mosca, Paul J. ; Pruitt, Scott K. ; Salama, April K S ; Chan, Cliburn ; Tyler, Douglas ; Weinhold, Kent J. / Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion. In: Annals of Surgical Oncology. 2013 ; Vol. 20, No. 4. pp. 1128-1135.
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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.",
author = "Gina Shetty and Beasley, {Georgia M.} and Sara Sparks and Michael Barfield and Melanie Masoud and Mosca, {Paul J.} and Pruitt, {Scott K.} and Salama, {April K S} and Cliburn Chan and Douglas Tyler and Weinhold, {Kent J.}",
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T1 - Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion

AU - Shetty, Gina

AU - Beasley, Georgia M.

AU - Sparks, Sara

AU - Barfield, Michael

AU - Masoud, Melanie

AU - Mosca, Paul J.

AU - Pruitt, Scott K.

AU - Salama, April K S

AU - Chan, Cliburn

AU - Tyler, Douglas

AU - Weinhold, Kent J.

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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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