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Due to the better survival of patients with tumorous diseases, it is increasingly important to predict the side effects of radiotherapy, for which the Radiation-Induced Lymphocyte Apoptosis (RILA) method is proving to be effective in multicentric studies. Prostate cancer is the leading cause of cancer-related deaths among men worldwide, which is usually treated with radiotherapy. We recruited 49 patients with localized prostate cancer and performed RILA measurements before radiotherapy. Patients were treated with CyberKnife (35–40 Gy) or high-dose-rate brachytherapy (1 × 21 Gy). We performed chromosome aberration test for five years and graded side effects, IPSS and QoL questionnaire scores were recorded. We found that RILA% correlated with the IPSS increase (p = 0.0016, r=-0.44), which was confirmed with negative binomial regression (p = 0.0013). The negative predictive value for severe urinary side effects according to the IPSS questionnaire was 87.9% at the lower tertile of RILA values. Chromosome aberrations also correlated with side effects, but when we built models including variables of baseline and treatment characteristics of the patients, RILA, and chromosome aberrations, only RILA predicted a late increase in IPSS score (p < 0.0001, adjusted R2 = 68%). The RILA method was shown to be predictive of urinary side effects especially of patient-reported outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the radiobiological effects of flattening filter (FF) and flattening filter-free (FFF) modes of linear electron accelerators and to understand whether there is any difference between the effects of these modes. We evaluated the number of chromosome aberrations following irradiation of lymphocytes from healthy volunteers with X-ray photons at two energy levels, 6 and 10 MV; the dose rate ranged between 5.50 and 23.08 Gy/min and absorbed doses ranged between 0.5 and 8 Gy. A 60Co curve was employed for comparison. Metaphases from the lymphocyte cultures were prepared using standard cytogenetic techniques and chromosome analysis was performed. Our results allow the performance of biodosimetry at higher energies and doses than the currently used reference dosimetry. We observed significant differences in aberration frequencies when different irradiation techniques were used. FFF mode has a higher radiobiological effect than the FF mode. Linear-quadratic dose response calibration curves were constructed and relative biological effectiveness (RBE) values were calculated. Average RBE values using 6 MV (5.50 Gy/min) as a reference radiation were 1.28 for 60Co γ irradiation, 1.11 for 6 FFF and 0.79–0.92 for 10 FFF. Since there are compelling differences between radiation modalities in cases of hypofractionation, these results may be even more important in a therapeutic situation. In case of an accidental overdose of a patient, use of the appropriate calibration curves for biodosimetry are also essential for quantifying the overdose. [ABSTRACT FROM AUTHOR]

Numerical and structural chromosomal abnormalities are the hallmarks of cancer. Whereas the structural chromosome aberrations got more substantial attention for cancer risk assessment in a healthy population, the role of aneuploidy is much less understood in this respect. We analysed the frequency of numerical (and structural) aberrations in peripheral blood lymphocytes of 2145 healthy individuals between 1989 and 2010, taking into account different biological- and exposureconditions. We also studied to what extent chromosome gains or losses may predict the probability of cancer. The average frequency of all aneuploid cells was 1.78 ± 0.06% in the entire study population, which increased linearly with age. Gender and smoking did not influence the values, however, occupational exposures did. The highest frequency of aneuploidy was found in chemical industryworkers (1.89 ± 0.05%) compared with the lowest value of medical radiation workers (1.44 ± 0.10%), respectively. No correlation was found between numerical and structural chromosomal aberrations. Cancer incidence followed for 1-23 years after the chromosome analysis showed a 1.26-fold relative risk (confidence interval: 1.02-1.58; P = 0.04) for those with higher frequency of aneuploid cells (1.82% vs. 1.44% in controls). Hypodiploidy had higher impact on the cancer risk than hyperdiploidy (1.72% vs. 0.10%). Our findings on the frequency of numerical aberrations in a healthy cohort represent the largest cytogenetic database from one laboratory with an unchanged mechanistic scoring method during a 30-year period, and provide basic information not only for genotoxicological studies but also confirm the association between numerical aberrations and cancer risk. [ABSTRACT FROM AUTHOR]

Though radiotherapy is a local therapy, it has systemic effects mainly influencing immune and inflammation processes. This has important consequences in the long-term prognosis and therapy individualization. Our objective was to investigate immune and inflammation-related changes in the peripheral blood of head and neck cancer patients treated with radiotherapy. Peripheral blood cells, plasma and blood cell-derived RNA were isolated from 23 patients before and at two time points after radiotherapy and cellular immune parameters, plasma protein changes and gene expression alterations were studied. Increased regulatory T cells and increased CTLA4 and PD-1 expression on CD4 cells indicated an immune suppression induced by the malignant condition, which was accentuated by radiotherapy. Circulating dendritic cells were strongly elevated before treatment and were not affected by radiotherapy. Decreased endoglin levels in the plasma of patients before treatment were further decreased by radiotherapy. Expression of the FXDR, SESN1, GADD45, DDB2 and MDM2 radiation-response genes were altered in the peripheral blood cells of patients after radiotherapy. All changes were long-lasting, detectable one month after radiotherapy. In conclusion we demonstrated radiotherapy-induced changes in systemic immune parameters of head and neck cancer patients and proposed markers suitable for patient stratification worth investigating in larger patient cohorts. [ABSTRACT FROM AUTHOR]

Radical cystectomy is the gold standard treatment in localized muscle-invasive bladder cancer according to today's guidelines. However, in many cases, surgery is not possible due to the patient's general condition, or the patient refuses bladder removal. In such cases, as well as in some selected patients suitable for surgery, trimodal organ preservation therapy is an alternative, which provides the patient with similar survival, local tumor control, so that 80% of patients retain their bladder. In some cases, due to complications or a muscle-invasive local recurrence in the bladder, the bladder may not be retained. At this point, a salvage cystectomy can still save the patient's quality of life and life. Adequate patient selection is a prerequisite for effective trimodal therapy. We summarize the components of organ-preserving treatment, including radiation therapy, its state-of-the-art technology, results and side effects. The results and toxicity of trimodal treatment are compared with those of radical cystectomy.

Healthcare workers may be occupationally exposed to low dose rate radiation or different chemicals during their work. There are strong associations between the increased frequency of spontaneous chromosomal aberrations in blood lymphocytes and the risk of cancer. Cytogenetic tests were conducted on 1240 healthy medical workers and cancer incidence was followed up between 1997-2018. Both structural and numerical chromosome aberrations were evaluated and the results were compared taking into account gender, age, and smoking. The frequency of aberrant cells was significantly higher in smoker males than in non-smokers (p=0.009). Within the same study period, there was no significant difference in chromosome aberrations between the potentially exposed group of workers and the control group. Among 82 cancer cases (6.6%) the most common tumors were breast (16), colon (12), lung (7) and thyroid gland cancers (7). Our analysis showed 7.3% cancer occurrence among smokers compared to 6.2% among non-smokers. These results suggest that in our cases cytogenetic effects of smoking are more deleterious than occupational exposures.

Flattening filter free mode (FFF) has been introduced in radiotherapy during the past decades, however, not much has been reported on its radiobiological effect. The purpose of our study was to compare the radiobiological effects of flattening filter and flattening filter free photon beams on chromosomal aberrations in peripheral blood lymphocytes. In our study the blood of the same healthy donor was irradiated with linear accelerator using both conventional flattening filter (FF) and FFF photon beams at dose rate of 3.57-23.08 Gy/min, using 6 or 10 MV. The dose-response calibration curves for dicentric + ring chromosomes induced by irradiation were fitted with linear-quadratic model. CABAS (Chromosomal Aberration Calculation Software) was used to prepare the curves. The coefficients and equations of the curves were calculated and compared with the results of other authors. We found significant differences in the number of aberrations at different irradiation parameters. Based on our results, FFF mode has a 10-20% higher biological effect than FF mode. These results can be used during radiotherapy or to estimate the biological doses in case of an accidental exposure to radiation.

Head and neck cancer patients are at high risk for secondary primary cancer (SPC) development. Mutagen hypersensitivity may be associated with elevated risk of SPC. A survey was made of SPC among 124 young (≤50 years) patients with squamous cell carcinoma of the head and neck who were enrolled in a pretreatment mutagen sensitivity investigation during 1996-2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantitating the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (>1 b/c) or not hypersensitive (≤1 b/c). The mean follow-up time was 64 months (range: 5-244 months). Eighteen patients (15%) developed a SPC. The 10-year estimated rate of SPC for hypersensitive (n=65) or not hypersensitive (n=59) patients were 17% and 30%, respectively (p=0.4272). Thirty-nine percent of SPC was developed after 10-year follow-up. The 5-year cancer-specific survival was 17% following the development of SPC. According to our findings, mutagen hypersensitivity does not increase the risk of developing SPC.