Chromosome Damage and Cell Proliferation Rates in In Vitro Irradiated Whole Blood as Markers of Late Radiation Toxicity After Radiation Therapy to the Prostate

Purpose: In vitro irradiated blood samples from prostate cancer patients showing late normal tissue damage were examined for lymphocyte response by measuring chromosomal aberrations and proliferation rate. Methods and Materials: Patients were selected from a randomized trial evaluating the optimal timing of dose-escalated radiation and short-course androgen deprivation therapy. Of 438 patients, 3% experienced grade 3 late radiation proctitis and were considered to be radiosensitive. Blood samples were taken from 10 of these patients along with 20 matched samples from patients with grade 0 proctitis. The samples were irradiated at 6 Gy and, along with control samples, were analyzed for dicentric chromosomes and excess fragments per cell. Cells in first and second metaphase were also enumerated to determine the lymphocyte proliferation rate. Results: At 6 Gy, there were statistically significant differences between the radiosensitive and control cohorts for 3 endpoints: the mean number of dicentric chromosomes per cell (3.26 +/- 0.31, 2.91 +/- 0.32; P=.0258), the mean number of excess fragments per cell (2.27 +/- 0.23, 1.43 +/- 0.37; P<.0001), and the proportion of cells in second metaphase (0.27 +/- 0.10, 0.46 +/- 0.09; P=.0007). Conclusions: These results may be a valuable indicator for identifying radiosensitive patients and for tailoring radiation therapy. (C) 2013 Elsevier Inc.