title: Lymphocyte radiosensitivity correlated with pelvic radiotherapy morbidity.
abstract: OBJECTIVE
  To test the hypothesis that, before treatment, prostate cancer patients who demonstrate a high yield of ex vivo radiation-induced micronucleus (MN) in G(0) lymphocytes represent a patient population with a greater-than-average risk of developing radiotherapy (RT)-related morbidity.
  
  
  METHODS
  We prospectively conducted the cytokinesis-block MN assay of peripheral blood lymphocytes (PBLs) in 38 prostate cancer patients. Before the initiation of RT, PBLs from each patient were irradiated (1-4 Gy). The mean patient age +/- SEM was 68.7 +/- 1.0 years. The clinical stage was T1 in 17, T2 in 15, and T3 in 6. The preoperative prostate-specific antigen level was < or =4 ng/mL in 5, 4-10 ng/mL in 18, and >10 ng/mL in 15. All patients underwent standardized pelvic external beam radiotherapy (range 41.4-50.4 Gy) and boost (range 16-26 Gy). The mean follow-up +/- SEM was 32.8 +/- 4.6 months. At the end of follow-up, a radiation oncologist scored the GI or GU morbidity according to the Radiation Therapy Oncology Group criteria without knowledge of the MN data.
  
  
  RESULTS
  We found that between the average reactors (n = 25; i.e., patients who had Grade 1 or less RT-related morbidity) and over reactors (n = 13; i.e., patients who developed Grade 2 or greater RT-related morbidity), the differences in the ex vivo radiation dose-response relationship of MN yield in PBLs were highly significant, especially at doses of > or =2 Gy. Also, the development of RT-related morbidity correlated with the radiation dose-response relationship of MN yield in PBLs before treatment, but did not correlate with any of the patients' clinical variables.
  
  
  CONCLUSIONS
  Our findings suggest that the pre-RT ex vivo radiation dose-response relationship of MN yield in PBLs may be a significant predictive factor for the development of GI or GU morbidity in prostate cancer patients after pelvic RT.
authors.affiliation: Department of Radiation Oncology, Leo W. Jenkins Cancer Center, East Carolina University Brody School of Medicine, Greenville, NC 27858, USA. leet@mail.ecu.edu
authors.forename: Tung-Kwang
authors.initials: TK
authors.lastname: Lee
authors.forename: Ron R
authors.initials: RR
authors.lastname: Allison
authors.forename: Kevin F
authors.initials: KF
authors.lastname: O'Brien
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Johnke
authors.forename: Karen I
authors.initials: KI
authors.lastname: Christie
authors.forename: James L
authors.initials: JL
authors.lastname: Naves
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Kovacs
authors.forename: Hyder
authors.initials: H
authors.lastname: Arastu
authors.forename: Ulf L
authors.initials: UL
authors.lastname: Karlsson
mesh_terms: D000368:Aged; D004307:Dose-Response Relationship, Radiation; D005767:Gastrointestinal Diseases / Q000209:etiology*; D006801:Humans; D008214:Lymphocytes / Q000097:blood / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D052801:Male Urogenital Diseases / Q000209:etiology*; D009017:Morbidity; D010388:Pelvis / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011836:Radiation Tolerance; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D014481:United States