Longitudinal cytokine expression during IMRT for prostate cancer and acute treatment toxicity.

Christensen, E., Pintilie, M., Evans, K.R., Lenarduzzi, M., Menard, C., Catton, C.N., Diamandis, E.P., Bristow, R.G.
Journal   Clin Cancer Res.
Species  
Analytes Measured   GM-CSF , IL-10 , IL-12 p70 , IL-2 , IL-6 , IL-8
Matrix Tested   Serum
Year   2009
Volume   15
Page Numbers   5576-83
Application   Cytokines and Chemokines
Abstract
PURPOSE: Proteomic profiling of patients undergoing intensity-modulated radiotherapy (IMRT) for prostate cancer can identify unique biomarkers that reflect acute toxicity in normal tissues. Our objectives were to measure inflammatory cytokine proteins during IMRT and assess the variability of individual proteomic signatures.

EXPERIMENTAL DESIGN: Forty-two patients with intermediate-risk prostate cancer were recruited as follows: group 1, definitive IMRT (78 Gy in 39 fractions, n = 22), and group 2, IMRT postprostatectomy (66 Gy in 33 fractions, n = 20). Blood/urine samples were collected at baseline and weekly during IMRT. Acute toxicity was graded weekly during radiotherapy using CTC-AE v3.0 criteria. Multiplexed immunoassays were used to quantify cytokines including granulocyte macrophage colony-stimulating factor, IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-1alpha, IL-2, IL6, IL-8, IL-10, and IL-12p70.

RESULTS: We observed positive correlations between cytokine expression between serum and plasma, but not between serum/plasma and urine. The Mann-Whitney test showed a significant increase in IFN-gamma and IL-6 during IMRT (P = 0.0077, 0.0035). Increasing IL-2 and IL-1 expression were associated with increased probability of acute gastrointestinal and genitourinary toxicity, respectively.

CONCLUSIONS: Determination of radiation-response signatures is feasible using multiplexed immunoassays and is a promising predictive early biomarker of toxicity outcomes.

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Multiplex
V-PLEX Viral Panel 2 Human Kit
IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α | Human
Multiplex
V-PLEX Viral Panel 1 NHP Kit
IL-1β, IL-6, IL-8 | Non-human primate
Multiplex
V-PLEX Viral Panel 1 Human Kit
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
V-PLEX Plus Viral Panel 2 NHP Kit
IFN-γ, IL-1β, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
U-PLEX NHP IL-2 Assay
IL-2 | Non-human primate
Singleplex
U-PLEX NHP IL-10 Assay
IL-10 | Non-human primate
Singleplex
U-PLEX NHP IL-8 Assay
IL-8 | Non-human primate
Singleplex
U-PLEX NHP IL-6 Assay
IL-6 | Non-human primate
Singleplex
U-PLEX NHP GM-CSF Assay
GM-CSF | Non-human primate
Singleplex
U-PLEX Mouse IL-12p70 Assay
IL-12p70 | Mouse
Singleplex
U-PLEX Mouse IL-10 Assay
IL-10 | Mouse
Singleplex
U-PLEX Mouse GM-CSF Assay
GM-CSF | Mouse
Singleplex
U-PLEX Mouse IL-6 Assay
IL-6 | Mouse
Singleplex
U-PLEX Mouse IL-2 Assay
IL-2 | Mouse
Singleplex
U-PLEX NHP IL-12p70 Assay
IL-12p70 | Non-human primate
Singleplex
U-PLEX Human GM-CSF Assay
GM-CSF | Human
Singleplex
U-PLEX Human IL-6 Assay
IL-6 | Human
Singleplex
U-PLEX Human IL-2 Assay
IL-2 | Human
Singleplex
U-PLEX Human IL-12p70 Assay
IL-12p70 | Human
Singleplex
U-PLEX Human IL-10 Assay
IL-10 | Human
Singleplex
U-PLEX Human IL-8 Assay
IL-8 | Human
Singleplex
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