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


METHODS
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.
Christensen
Eva
E
Radiation Medicine Program, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
Pintilie
Melania
M
Evans
Kenneth R
KR
Lenarduzzi
Michelle
M
Ménard
Cynthia
C
Catton
Charles N
CN
Diamandis
Eleftherios P
EP
Bristow
Robert G
RG
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000652:urine; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D040901:Proteomics; D011829:Radiation Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*
D015415:Biomarkers; D016207:Cytokines