One of the challenges of radiation oncology in the era of personalized medicine is identification of biomarkers associated with individual radiosensitivity. The aim of research was to evaluate the possible clinical value of the associations between clinical, physical, and biological factors, and risk for development of acute radiotoxicity in patients with prostate cancer. The study involved forty four patients treated with three-dimensional conformal radiotherapy. The concentrations of IL-1β, IL-2, IL-6, IFN-γ and TGF-β1 were assessed before radiotherapy, after 5th, 15th and 25th radiotherapy fractions, at the end, and 1 month after the end of radiotherapy. Cytokine gene expression was determined in peripheral blood mononuclear cells. The univariate analysis of circulating cytokine levels during radiotherapy showed that increased serum concentrations of IL-6 were significantly associated with higher grade of acute genitourinary toxicity. The multivariate analysis demonstrated that increased level of IL-6 during the radiotherapy was significantly associated with higher grade of acute genitourinary toxicity across treatment. TGF-β expression levels significantly decreased during course of radiotherapy. Research indicates that changes in circulating cytokine levels might be important parameter of radiotoxicity in patients with prostate cancer. These findings suggest that future studies based on multi-parameter examination are necessary for prediction of individual radiosensitivity.

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The genetic background of each person might affect the severity of radiotherapy (RT)-induced normal tissue toxicity. The aim of study was to evaluate the influence of TGFB1 C-509T and Leu10Pro, XRCC1 Arg280His and XRCC3 Thr241Met polymorphisms as well as the level of radiation-induced CD8 T-lymphocyte apoptosis (RILA) on adverse effects of RT for prostate cancer (PCa). The study included 88 patients with localized or locally advanced PCa who were treated with RT. The polymorphisms were determined by PCR–RFLP analysis on DNA from peripheral blood mononuclear cells. RILA values were measured by flow cytometry. We found that CT genotype of TGFB1 C-509T could be protective biomarker for acute genitourinary (GU) and gastrointestinal (GI) radiotoxicity, while Thr variant of XRCC3 Thr241Met could predict the risk for acute GU radiotoxicity. Correlation between RILA values and toxicity was not detected. Univariate logistic regression analysis showed that Gleason score and risk group were risk factors for late GU, while for late GI radiotoxicity it was diabetes mellitus type 2. However, in multivariate model those were not proven to be significant and independent risk factors. Identification of assays combination predicting individual radiosensitivity is a crucial step towards personalized RT approach.

Background The goal of research was to investigate the possible relations between serum concentrations of IL-6 and TGF-β1, individual and clinical characteristics, and adverse effects of radiotherapy in patients with prostate cancer: acute and late genitourinary and gastrointestinal toxicity, and fatigue. Methods Thirty-nine patients with localized or locally advanced prostate cancer who were treated with radiotherapy were enrolled in this study. The acute radiotoxicity grades and fatigue levels were assessed during the radiotherapy and 1 month after the radiotherapy. Estimation of the late radiotoxicity was performed every three months in the first year, every four months in the second year, and then every six months. Serum levels of IL-6 and TGF-β1 were determined before radiotherapy and after the 25th radiotherapy fraction by ELISA. Results The significant positive association between diabetes mellitus and changes in acute genitourinary toxicity grades during the radiotherapy was observed in prostate cancer patients. In addition, patients who were smokers had significantly higher maximum fatigue levels in comparison with patients who were non-smokers. The circulating IL-6 levels were significantly higher after the 25th radiotherapy fraction in comparison with levels determined before radiotherapy. The significant positive correlations between pretreatment TGF-β1 levels and maximum genitourinary toxicity grades and between TGF-β1 levels after the 25th fraction and genitourinary toxicity grades after the 25th fraction, were found. The pretreatment IL-6 concentrations and TGF-β1 concentrations after the 25th fraction were positively correlated with maximum genitourinary toxicity grades. The IL-6 levels after the 25th fraction were positively associated with genitourinary toxicity grades after this fraction. The pretreatment IL-6 concentrations were significantly positively correlated with maximum fatigue scores. The significant positive correlation between IL-6 concentrations and fatigue scores after the 25th fraction was determined. The positive correlations between IL-6 and TGF-β1 concentrations measured after the 25th fraction and maximum fatigue scores were observed. Conclusions Our results suggest that serum levels of IL-6 and TGF-β1 might influence the severity of acute genitourinary radiotoxicity and fatigue in patients with prostate cancer. Combining clinical parameters and circulating cytokine levels might be useful for the prediction of adverse reactions to radiotherapy.

Our aim is to estimate incidence and prevalence rates as well as overall changes in the degree of late urogenital toxicity (UGT) over time in patients treated with 3D conformal radiotherapy (3DCRT) for localized prostate cancer (PC) and to explored possible predictive factors for late UGT.Ninety-four patients with localized PC, treated with 3DCRT with a total dose of 72Gy/2Gy/daily, were examined in this study. The median follow-up was 66 months. Many individual and clinical characteristics were explored as possible predictive factors for late UGT.Incidences of late UGT grade ≥1, ≥2 and grade 3 were 64.89% (61/94), 22.34% (21/94) and 7.4% (7/94), respectively. The prevalence rates of late UGT grade ≥1, grade ≥2 and grade 3 were 26.6%-36.3%, 3.2-13.3% and 1.06%-7.89%, respectively. Statistically significant positive trend was found favoring an increase in the degree of late UGT over time (b=0.028; p<0.001). In the MVA, previous abdominal and pelvic surgery (PAPS) and acute UGT were significantly associated with late UGT grade≥1 (p=0.007) and (p=0.013), respectively.We can conclude that the degree of late UGT increases over time. PAPS and the occurrence of any grade of acute UGT have a significant influence on the development of any grade of late UGT.