title: Early hematologic changes during prostate cancer radiotherapy predictive for late urinary and bowel toxicity.
abstract: BACKGROUND
  The primary objective of the study was to identify early hematologic changes predictive for radiotherapy (RT)-associated genitourinary and gastrointestinal toxicity.
  
  
  METHODS
  In a group of 91 prostate cancer patients presenting for primary (n = 51) or postoperative (n = 40) curative RT, blood samples (blood count, acute phase proteins, and cytokines) were analyzed before (T1), three times during (T2-T4), and 6-8 weeks after (T5) radiotherapy. Before RT (baseline), on the last day (acute toxicity), a median of 2 months and 16 months (late toxicity) after RT, patients responded to a validated questionnaire (Expanded Prostate Cancer Index Composite). Acute score changes > 20 points and late changes > 10 points were considered clinically relevant.
  
  
  RESULTS
  Radiotherapy resulted in significant changes of hematologic parameters, with the largest effect on lymphocytes (mean decrease of 31-45 %) and significant dependence on target volume. C-reactive protein (CRP) elevation > 5 mg/l and hemoglobin level decrease ≥ 5 G/1 at T2 were found to be independently predictive for acute urinary toxicity (p < 0.01, respectively). CRP elevation was predominantly detected in primary prostate RT (p = 0.02). Early lymphocyte level elevation ≥ 0.3G/l at T2 was protective against late urinary and bowel toxicity (p = 0.02, respectively). Other significant predictive factors for late bowel toxicity were decreasing hemoglobin levels (cut-off ≥ 5 G/l) at T2 (p = 0.04); changes of TNF-α (tumor necrosis factor; p = 0.03) and ferritin levels (p = 0.02) at T5. All patients with late bowel toxicity had interleukin (IL)-6 levels < 1.5 ng/l at T2 (63 % without; p = 0.01).
  
  
  CONCLUSIONS
  Early hematologic changes during prostate cancer radiotherapy are predictive for late urinary and bowel toxicity.
authors.affiliation: Department of Radiation Oncology, RWTH Aachen University, Pauwelsstrasse 30, 52057, Aachen, Germany. MPinkawa@ukaachen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Pinkawa
authors.affiliation: Department of Diagnostic and Interventional Radiology, RWTH Aachen University, Pauwelsstrasse 30, 52057, Aachen, Germany.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ribbing
authors.affiliation: Department of Radiation Oncology, RWTH Aachen University, Pauwelsstrasse 30, 52057, Aachen, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Djukic
authors.affiliation: Department of Radiation Oncology, RWTH Aachen University, Pauwelsstrasse 30, 52057, Aachen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Klotz
authors.affiliation: Department of Radiation Oncology, RWTH Aachen University, Pauwelsstrasse 30, 52057, Aachen, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Holy
authors.affiliation: Department of Radiation Oncology, RWTH Aachen University, Pauwelsstrasse 30, 52057, Aachen, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Eble
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D001772:Blood Cell Count; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D041981:Gastrointestinal Tract / Q000528:radiation effects*; D006452:Hemoglobinometry; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D011788:Quality of Life; D011832:Radiation Injuries / Q000097:blood* / Q000175:diagnosis*; D018714:Radiotherapy, Adjuvant; D014566:Urogenital System / Q000528:radiation effects*
chemical_list: D000209:Acute-Phase Proteins; D016207:Cytokines; D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: C-reactive protein; Hemoglobin; Intensity-modulated radiotherapy; Predictive assays; Quality of life