BERKELEY, CA (UroToday.com) - An intriguing observation is that patients differ significantly in normal tissue response even after similar radiotherapy schemes, indicating individual variations of the intrinsic radiosensitivity. A high cellular radiosensitivity may be connected with a risk for development of severe side effects after radiotherapy and indicate cancer susceptibility. The discrimination between radiosensitive and radioresistant individuals before the onset of treatment would be of great importance for an optimized and individualized radiotherapy and consequently for a patient’s life expectancy and quality. Hence, a fast and robust in vitrotest is desirable to identify radiosensitive individuals.
A high frequency of chromosomal aberrations in peripheral blood lymphocytes has been suggested to be a marker for intrinsic radiosensitivity. The aim of this study was to compare the individual cellular radiosensitivity of prostate cancer patients with and without severe clinical side effects after radiotherapy and age-matched healthy donors using the following assays: G2-assay (chromatid aberrations due to irradiation in the G2-phase of the cell cycle), γ-H2AX-assay (measurement of histone H2A phosphorylation), and apoptosis assay. The study included 25 prostate cancer patients with and 25 patients without severe side effects after radiotherapy as well as 23 male healthy age-matched donors. In order to analyse equal sample sizes for all groups of donors the patients were selected retrospectively according to their clinical reactions after radiotherapy assessed with the validated EPIC questionnaire (Expanded Prostate Cancer Index Composite). Blood samples were exposed to 0.5 Gy or 1 Gy of γ–rays.
The mean γ-H2AX foci numbers were comparable in all groups of blood donors. No significant differences in early apoptosis level resulted between patients with and without clinical side effects or between any patients groups and healthy donors. This indicates that Annexin V/PI assay alone is not a good indicator for both, cancer susceptibility and normal tissue response to radiotherapy as well.
A significantly higher aberration yield was observed for both spontaneous (p<0.05) and radiation-induced (p<0.05) aberrations in patients with side effects (S) when compared to healthy donors. A significant difference was found in radiation-induced aberration yields in patients without side effects (0) in comparison with healthy donors (p<0.05). No significant difference was observed in the aberration yield between patients with and without side effects. A correlation between clinical and chromosomal (due to radiation-induced aberrations) radiosensitivity observed in this study was true for 50% of the analysed prostate cancer patients. However, only 25% of the analysed prostate cancer patients showed both clinical side effects and enhanced chromosomal radiosensitivity.
The obtained success rate is not sufficient to use the G2-assay as a good tool for the identification of prostate cancer patients with a high risk for development of severe clinical side effects. There is no obvious correlation between clinical and cellular radiosensitivity in lymphocytes of prostate cancer patients when all chosen in vitro assays are considered. Further investigations using other in vitro assays such as single nucleotide polymorphism analysis or a combination of assays might be more useful.
Written by:
Michael Pinkawa, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
