Session Item

To perform a detailed analysis of the systemic immune status and change in cytogenetic parameters of prostate cancer patients treated with various radiotherapy protocols in order to mark potential biomarkers for patient follow-up.

Blood samples were collected before and after radiotherapy, PBM cells were investigated by flow cytometry, chromosome aberration technique was applied, protein profile of plasma samples of LDR patients were analysed by LEGENDplex assays

Chromosome aberrations increased after radiotherapy (HDR: 3.4±0,5 to 5.5±0.8; LDR: 2.9±0.4 to 6.4±0.5; EBRT: 4.2±0.4 to 17.2±1.9; Cyberknife: 4.5±0,5 to 11.3±1.5 total aberrations/100 cells). 1.8% Gr 3 acute genitourinal (GU) side effects were observed. ≤ Gr 2 late GU toxicities were found after LDR therapy (49.0%), the less after HDR treatment (18.5%). There were 3.4% late GI side effects. IPSS questionnaire indicated the highest distress after the last fraction of teletherapies (EBRT: 16.8±1.4, Cyberknife: 16.9±1.2). Chromosome fragments frequency predicted cumulative GU toxicities 3 months after HDR therapy (Pearson corr. coeff. 0.49). Radiation induced lymphocyte apoptosis (RILA) was also measured to identify radiosensitive patients. Correlation and regression analysis showed that RILA values and chromosome aberration results are consistent. An increased level of total circulating NK cells was detected 3 months after in LDR BT patients and remains elevated up to 36 months compared to control group (CG) and pre-treatment values as well. In HDR patients mature NK cell level decreased, while degranulating and anergic NK cell levels significantly increased compared to CG. The level of lymphoid DCs showed the same pattern in both patients groups; it was increased in patients before therapy and remained unchanged up to 6 months after therapy initiation. Changes of myeloid DCs was different; in LDR patients elevated up to 12 months after the implantation, however in HDR group their level was near to average of healthy controls. Cancer significantly reduced naïve and activated CD8 cells and increased senescent CD8 and CD4 cells in HDR patients compared to CG. Effector memory T cells increased in HDR-treated patients 3 month after treatment compared to pre-treatment values, T stem cell memory, central memory and terminal memory T cell levels remained below control values up to 36 months.

Radiotherapy can influence the changes of cellular and soluble markers in LDR and HDR patient groups as well. The increases of lymphoid DCs, of the immature and degranulating NK cells are acute effects of BT, while the increase of total circulating and anergic NK cells, the activated and early-senescence CD8 and CD4 T cells and the decrease of central and terminal memory T cells are late persistent chronic effects of radiotherapy. Immunological values changed in parallel with cytogenetic parameters, suggesting their use as predictive indicator of toxicity.