Radiotherapy Technique Determines the Magnitude and Persistence of T-Lymphocyte DNA Damage

Background: There are limited data comparing the effect of different radiotherapy techniques on healthy cells in the same patient group. Furthermore, assessing radiotherapy-induced T-lymphocyte damage may be important given the increasing use of immunotherapy. We aimed to measure and compare DNA damage in T-lymphocytes after four types of radiotherapy for low- and intermediate-risk prostate cancer and monitor their persistence for five years. Methods: A prospective comparison of patients receiving conventional LINAC (linear accelerator) (70–78 Gy), CyberKnife teletherapy (37.5–40 Gy), low-dose-rate brachytherapy (LDR; 145 Gy) and high-dose-rate brachytherapy (HDR; 19–21 Gy was performed using the chromosome aberration technique (at 3, 6, 9, 12, 24, 36, 48, and 60 months, 192 patients). Multivariate regression analyses were conducted to assess the predictive potential of chromosome aberrations for toxicities. Results: We found that teletherapy techniques (conventional LINAC and CyberKnife therapy) caused 1.6–3.6-fold more chromosomal aberrations than brachytherapy. At three months, 4.4–13.1% of T-lymphocytes were damaged. Five years after treatment, the total aberration values of conventional LINAC and LDR brachytherapy patients were still significantly higher than those before treatment (p < 0.001 for LINAC and p = 0.011 for LDR). Significant regression models suggested that total aberrations or aberrant cell frequency might predict toxicities in addition to the biologically effective dose (BED) and the irradiated volume (V100%) (p = 0.020 for the model including total aberrations, p = 0.010 for the model including aberrant cell frequency). Conclusions: We observed a lower chromosome aberration frequency and fewer toxicities in brachytherapy patients. We also demonstrated that long-term T-lymphocyte damage depends on the type of radiotherapy.