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.

Background As the assessment of lymphocyte damage caused by radiotherapy gains importance as immunotherapies are used more frequently. Furthermore, there is scarce data to compare the biological dose of radiotherapy techniques in the same patient group. Methods Applying chromosome aberration technique, a five-year long (at 3, 6, 9, 12, 24, 36, 48, 60 months) prospective comparison of the biological impact of four different types of treatments for low- and intermediate-risk prostate cancer was performed (195 patients): conventional LINAC (linear accelerator) (70-78 Gy) and Cyberknife (40-37.5 Gy) teletherapy, LDR (low dose rate brachytherapy, 145 Gy) and HDR (high dose rate brachytherapy 19/21 Gy). Multivariate regression analyses were performed to analyze the predictive potential of the chromosome aberrations on side effects. The median follow-up was 48-60 months. Results We have found that teletherapy techniques (conv. LINAC and Cyberknife therapy) caused 1.7–3.2-fold more chromosomal aberrations than brachytherapies. At three months, 4.6%– 12.7% of the lymphocytes were damaged. Five years after treatment, the total aberration values of conventional LINAC and LDR brachytherapy patients were still significantly higher than before the therapy (p=0.035 for LINAC and p=0.003 for LDR BT). We found significant regression models suggesting chromosome aberration might predict side effects beside radiation dose and irradiated volumes (V100%): Late genitourinary (GU) side effects were dependent of chromosome fragments directly after conv. LINAC therapy (p=0.005). Conclusions We demonstrated long-term lymphocyte damage dependent on the type of radiotherapy. We also found less biological dose and side effects in brachytherapy patients. Highlights ### Competing Interest Statement The authors have declared no competing interest. * BT : brachytherapy CTV : clinical target volume EORTC-RTOG : European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group FBS : fetal bovine serum GI : gastrointestinal GU : genitourinary GS : gleason score HDR : high dose rate HT : hormone therapy IPSS : International prostate symptom score LDR : low dose rate LINAC : linear accelerator PROM : patient-reported outcome measure PTV : planning target volume SIB : simultaneous integrated boost QoL : quality of life V100% : volume, which received the 100% of the prescribed dose the National Research, Development and Innovation Fund of the Ministry of Culture and Innovation, 2022-2.1.1-NL-2022-00010, TKP2021-EGA-44, 2020-1.1.6-JÖVŐ-2021-00008

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.

AIM:Daily online adaptive radiation therapy (OART) allows the creation of individualized safety margins based on daily optimized treatment planning, taking into account daily anatomy variations. The goal of our work was to compare the protocols and safety margins of a non-adapted, image- guided radiation therapy (IGRT), a published Danish and the National Institute of Oncology of Hungary (NIO) protocol in the first eight bladder cancer patients treated with OART. METHODS:Three cone beam CTs (CBCT) were taken during the first three fractions: after patient positioning, after adaptation, and at the end of treatment. Bladder contours, extensions and margins were established on all CT images (n=512). Intraadaptational, intrafractional and interfractional changes were examined. RESULTS:Regarding PTV, a mean reduction of 12.2% could be achieved using the Danish, and 34.1% using the NIO protocol compared to IGRT. Healthy tissue irradiated by the prescribed dose could be reduced. The target volume miss is decreased as well. CONCLUSIONS:PTV could be reduced and optimized, increasing healthy tissue protection using OART.

External radiation therapy for bladder cancer requires large planning target volumes (PTVs) due to the daily anatomy of the bladder. Online adaptive radiotherapy (oART) can reduce the PTV by considering daily anatomical changes. We performed oART in 8 patients with muscle-invasive bladder cancer between June 10, 2022, and April 14, 2023, on an Ethos linear accelerator (Varian, Palo Alto, USA). Using the 496 cone-beam computed tomography (CBCT) images of the fractions, we retrospectively compared the differences in volumetric changes between oART and image-guided and intensity-modulated radiotherapy (IGRT/IMRT). According to our local protocol, for oART, a patient-specific PTV margin was created based on the intrafractional clinical target volume (CTV) changes observed during the first three fractions. The average duration of treatment was 14.8 min (range 7–49 min). The average volume of the PTV with oART and IGRT/IMRT was 296.8 cm3 (range 114.5–810.4 cm3) and 416.5 cm3 (range 188.2–991.3 cm3), respectively, representing a 30

While exposure times of several hours or more are needed for AMPA or kainate to induce widespread cortical neurodegeneration, the small subset of cortical neurons that contain high concentrations of the enzyme, NADPH-diaphorase (NADPH-d(+) neurons) were destroyed by brief (15 30 min) exposures. AMPA or kainate-induced degeneration of NADPH-d(+) neurons was decreased by removal of extracellular Ca2+ and increased by augmentation of extracellular Ca2+, More than 90% of NADPH-d(+) neurons exhibited kainate-activated Co2+ uptake, suggesting that they possess Ca2+-permeable AMPA/kainate receptor-gated channels. The heightened vulnerability of NADPH-d(+) neurons to AMPA or kainate toxicity may reflect rapid Ca2+ entry through these Ca2+-permeable channels.

Due to the profound difference in radiosensitivity of patients and various side effects caused by this phenomenon, a radiosensitivity marker is needed. Prediction by a marker may help personalise the treatment. In this study, we tested chromosomal aberrations (CA) of in vitro irradiated blood as predictor of pulmonary function decrease of nonsmall cell lung cancer (NSCLC) patients and also compared it with the CAs in the blood of irradiated patients. Peripheral blood samples were taken from 45 lung cancer patients before stereotactic radiotherapy (SBRT) and immediately after the last fraction and 3, 6, 9, 12, 15, 18, 21, and 24 months later. Respiratory function measurements were performed at the same time. Diffusing capacity of lung for carbon monoxide (DLCO), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1s), and FEV1s/FVC (FEV1%) were monitored. Metaphase preparations of lymphocytes were made with standard procedures, and chromosome aberrations were analysed. In our cohort, the 36-month local relapse-free survival was 97.4%, and the distant metastasis-free survival was 71.5% at 36 months. There was no change in the mean of the pulmonary function tests (PFTs) after the therapy. However, there was a considerable variability between the patients. Therefore, we subtracted the baseline and normalised the PFT values. There were significant decreases at 12–24 months in relative FEV1s and relative FEV1%. The tendentious decrease of the PFTs could be predicted by the in vitro chromosome aberration data. We also found connections between the in vitro and in vivo CA values (i.e., dicentrics plus rings after 3 Gy irradiation predicts dicentric-plus-ring value directly after the radiotherapy/V54 Gy (p = 0.001 24.2%)).We found that—after further validation—chromosome aberrations resulted from in vitro irradiation before radiotherapy can be a predictive marker of pulmonary function decrease after lung irradiation.

BACKGROUND:The aim of the study was to dosimetrically compare multicatheter interstitial brachytherapy (MIBT) and stereotactic radiotherapy with CyberKnife (CK) for accelerated partial breast irradiation (APBI) especially concerning the dose of organs at risk (OAR-s). PATIENTS AND METHODS:Treatment plans of thirty-two MIBT and CK patients were compared. The OAR-s included ipsilateral non-target and contralateral breast, ipsilateral and contralateral lung, skin, ribs, and heart for left-sided cases. The fractionation was identical (4 x 6.25 Gy) in both treatment groups. The relative volumes (e.g. V100, V90) receiving a given relative dose (100%, 90%), and the relative doses (e.g. D0.1cm3, D1cm3) delivered to the most exposed small volumes (0.1 cm3, 1 cm3) were calculated from dose-volume histograms. All dose values were related to the prescribed dose (25 Gy). RESULTS:Regarding non-target breast CK performed slightly better than MIBT (V100: 0.7% vs. 1.6%, V50: 10.5% vs. 12.9%). The mean dose of the ipsilateral lung was the same for both techniques (4.9%), but doses irradiated to volume of 1 cm3 were lower with MIBT (36.1% vs. 45.4%). Protection of skin and rib was better with MIBT. There were no significant differences between the dose-volume parameters of the heart, but with MIBT, slightly larger volumes were irradiated by 5% dose (V5: 29.9% vs. 21.2%). Contralateral breast and lung received a somewhat higher dose with MIBT (D1cm3: 2.6% vs. 1.8% and 3.6% vs. 2.5%). CONCLUSIONS:The target volume can be properly irradiated by both techniques with similar dose distributions and high dose conformity. Regarding the dose to the non-target breast, heart, and contralateral organs the CK was superior, but the nearby organs (skin, ribs, ipsilateral lung) received less dose with MIBT. The observed dosimetric differences were small but significant in a few parameters at the examined patient number. More studies are needed to explore whether these dosimetric findings have clinical significance.

OBJECTIVE: To compare dosimetrically the stereotactic CyberKnife (CK) therapy and multicatheter high-dose-rate (HDR) brachytherapy (BT) for accelerated partial breast irradiation (APBI). METHODS: Treatment plans of 25 patients treated with CK were selected, and additional plans using multicatheter HDR BT were created on the same CT images. The prescribed dose was 6.25/25 Gy in both plans to the target volume (PTV). The dose-volume parameters were calculated for both techniques and compared. RESULTS: The D90 total dose of the PTV was significantly lower with CK than with HDR BT, D90 was 25.7 Gy, and 27.0 Gy (p < 0.001). However, CK plans were more conformal than BT, COIN was 0.87, and 0.81 (p = 0.0030). The V50 of the non-target breast was higher with CK than with BT: 10.5% and 3.3% (p = 0.0010), while there was no difference in the dose of the contralateral breast and contralateral lung. Dose to skin, ipsilateral lung, and ribs were higher with CK than with BT: D1 was 20.6 Gy vs. 11.5 Gy (p = 0.0018) to skin, 11.4 Gy vs. 9.6 Gy (p = 0.0272) to ipsilateral lung and 18.5 Gy vs. 12.3 Gy (p = 0.0013) to ribs, while D-0.1 to heart was lower, 3.0 Gy vs. 3.2 Gy (p =0.0476), respectively. CONCLUSIONS: Multicatheter HDR BT yields more advantageous plans than stereotactic CyberKnife treatment in accelerated partial breast irradiation, except in terms of dose conformality and the dose to the heart. There was no difference in the dose of the contralateral breast and lung. (C) 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

To evaluate the acute and late toxicity using moderately hypofractionated, intensity-modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) to prostate for patients with intermediate and high risk prostate cancer. From 2015 to 2017, 162 patients were treated with IMRT with SIB to the prostate. IMRT plans were designed to deliver 50.4Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes (whole pelvis radiotherapy, WPRT) while simultaneously delivering 57.4 Gy in 28 fractions (2.05 Gy/fraction) to the seminal vesicles and 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate for high risk patients. For intermediate risk patients the same technique was applied, without WPRT. Acute and cumulative late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) scoring system. Of the 162 patients enrolled, 156 (96%) completed the treatment as planned. The median follow-up time was 30 months. Seventy-eight patients (48.2%) were treated with WPRT. The rate of acute grade ≥ 2 GI and GU toxicities in all patients were 22% and 58%, respectively. The rate of cumulative late grade ≥ 2 GI and GU toxicities were 11% and 17%, respectively. Acute grade 3 GI and GU toxicities occurred in 1% and 1%. Late grade 3 GI and GU side effects occurred in 5% and 4%, respectively. None of the patients developed grade ≥ 4 toxicity. IMRT with SIB technique using moderate hypofractionation to the prostate is feasible treatment option for intermediate and high risk patients, associated with low rate of severe GU and GI toxicities.

Three-dimensional finite element numerical model calculations have been carried out to investigate the quantitative effect of the eccentric position of a normal resistivity borehole probe used in practice. Detailed calculations were done between the point-wise analytical solution and numerical solution to verify the results obtained from the finite element method for a normal probe with finite-length cylindrical electrodes. In the borehole the pattern of the current flowing out from current electrode A is efficiently influenced by the eccentricity. For high-resistivity rock the current density is decreased, while for low-resistivity rock it is increased toward the wall side. On the other hand, the eccentricity does not affect considerably the apparent resistivity calculated from electrode potentials. In most geological situations the deviation is less than 2%. However, in infrequent cases when the true resistivity of the rock is extremely low and/or the distance between the potential and current electrodes is very small the effect of the eccentricity can exceed even 10%.

The purpose of our work was to compare intraoperative and four-week post-implant dosimetry for loose and stranded seed implants for permanent prostate implant brachytherapy. In our institute low-dose-rate (LDR) prostate brachytherapy is performed with encapsulated I-125 isotopes (seeds) using transrectal ultrasound guidance and metal needles. The SPOT PRO 3.1 (Elekta, Sweden) system is used for treatment planning. In this study the first 79 patients were treated with loose seed (LS) technique, the consecutive patients were treated with stranded seed (SS) technique. During intraoperative planning the dose constraints were the same for both techniques. All LSs were placed inside the prostate capsule, while with SS a 2 mm margin around the prostate was allowed for seed positioning. The prescribed dose for the prostate was 145 Gy. This study investigated prostate dose coverage in 30-30 randomly selected patients with LS and SS. Four weeks after the implantation native CT and MRI were done and CT/MRI image fusion was performed. The target was contoured on MRI and the plan was prepared on CT data. To assess the treatment plan dose-volume histograms were used. For the target coverage V100, V90, D90, D100, for the dose inhomogeneity V150, V200, and the dose-homogeneity index (DHI), for dose conformality the conformal index (COIN) were calculated. Intraoperative and postimplant plans were compared. The mean V100 values decreased at four-week plan for SS (97% vs. 84%) and for LS (96% vs. 80%) technique, as well. Decrease was observed for all parameters except for the DHI value. The DHI increased for SS (0.38 vs. 0.41) and for LS (0.38 vs. 0.47) technique, as well. The COIN decreased for both techniques at four-week plan (SS: 0.63 vs. 0.57; LS: 0.67 vs. 0.50). All differences were significant except for the DHI value at SS technique. The percentage changes were not significant, except the COIN value. The dose coverage of the target decreased significantly at four-week plans for both techniques. The decrease was larger for LS technique, but the difference between techniques was not significant at this patient number. The dose distribution was more homogenous, but the conformality was worse at four-week plans.

PURPOSE:To compare target volume coverage and critical organ dosimetry of intraoperative treatment plans for loose seed (LS) and stranded seed (SS) (125)I permanent implants for low and intermediate risk prostate cancer. METHODS:Two hundred and five patients who underwent permanent seed brachytherapy were included in the study. For prostate dosimetry V90, V100, V150, V200, D90 and COIN were used. The dose to urethra and rectum was determined by the maximal dose and relative doses that cover specified volumes. Means and standard deviations were calculated and statistically compared. RESULTS:On average, 54 (range, 30-78) and 48 (range, 31-67) seeds were implanted in the prostate with individual median activities of 0.62 U (range, 0.52-0.70 U) and 0.71 U (range, 0.65-0.71 U) for LS and SS technique, respectively. The target coverage was slightly better with SS (V100: 98% vs. 96%,p < 0.05; D90: 172 Gy vs. 166 Gy, p < 0.05), but more conformal dose distributions were observed with LS (COIN: 0.70 vs. 0.63, p < 0.05). The dose homogeneity did not differ significantly between the two groups. Regarding the dose to urethra and rectum all dose parameters were significantly lower with LS. CONCLUSIONS:LS resulted in less dose to the urethra and rectum compared to SS in intraoperative dosimetry. A slightly better target volume coverage with decreased conformity of dose distribution is reported with SS. More studies are necessary to determine how these results will affect postoperative dosimetry, and ultimately, clinical outcome.