title: Longitudinal cytokine expression during IMRT for prostate cancer and acute treatment toxicity.
abstract: 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.
authors.affiliation: Radiation Medicine Program, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Eva
authors.initials: E
authors.lastname: Christensen
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Evans
authors.forename: Michelle
authors.initials: M
authors.lastname: Lenarduzzi
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ménard
authors.forename: Charles N
authors.initials: CN
authors.lastname: Catton
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
mesh_terms: 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*
chemical_list: D015415:Biomarkers; D016207:Cytokines