Introduction: In radiology, low X-ray energies (<140 keV) are used to obtain an optimal image while in radiotherapy, higher X-ray energies (MeV) are used to eradicate tumor tissue. In radiation research, both these X-ray energies being used to extrapolate in vitro research to clinical practice. However, the energy deposition of X-rays depends on their energy spectrum, which might lead to changes in biological response. Therefore, this study compared the DNA damage response (DDR) in peripheral blood lymphocytes (PBLs) exposed to X-rays with varying beam quality, mean photon energy (MPE) and dose rate.Methods: The DDR was evaluated in peripheral blood lymphocytes (PBLs) by the ɣ-H2AX foci assay, the cytokinesis-block micronucleus assay and an SYTOX-based cell death assay, combined with specific cell death inhibitors. Cell cultures were irradiated with a 220 kV X-ray research cabinet (SARRP, X-Strahl) or a 6 MV X-ray linear accelerator (Elekta Synergy). Three main physical parameters were investigated: beam quality (V), MPE (eV) and dose rate (Gy/min). Additional copper (Cu) filtration caused variation in the MPE (78 keV, 94 keV, 118 keV) at SARRP; dose rates were varied by adjusting tube current for 220 kV X-rays (0.33-3 Gy/min) or water-phantom depth in the 6 MV set-up (3-6 Gy/min).Results: The induction of chromosomal damage and initial (30 min) DNA double-stranded breaks (DSBs) were significantly higher for 220 kV X-rays compared to 6 MV X-rays, while cell death induction was similar. Specific cell death inhibitors for apoptosis, necroptosis and ferroptosis were not capable of blocking cell death after irradiation using low or high-energy X-rays. Additional Cu filtration increased the MPE, which significantly decreased the amount of chromosomal damage and DSBs. Within the tested ranges no specific effects of dose rate variation were observed.Conclusion: The DDR in PBLs is influenced by the beam quality and MPE. This study reinforces the need for consideration and inclusion of all physical parameters in radiation-related studies.

BACKGROUND:Prostate cancer patients treated with radiotherapy are susceptible to acute gastrointestinal (GI) toxicity due to substantial overlap of the intestines with the radiation volume. Due to their intimate relationship with GI toxicity, faecal microbiome and metabolome dynamics during radiotherapy were investigated. MATERIAL & METHODS:This prospective study included 50 prostate cancer patients treated with prostate (bed) only radiotherapy (PBRT) (n = 28) or whole pelvis radiotherapy (WPRT) (n = 22) (NCT04638049). Longitudinal sampling was performed prior to radiotherapy, after 10 fractions, near the end of radiotherapy and at follow-up. Patient symptoms were dichotomized into a single toxicity score. Microbiome and metabolome fingerprints were analyzed by 16S rRNA gene sequencing and ultra-high-performance liquid chromatography hybrid high-resolution mass spectrometry, respectively. RESULTS:The individual α-diversity did not significantly change over time. Microbiota composition (β-diversity) changed significantly over treatment (PERMANOVA p-value = 0.03), but there was no significant difference in stability when comparing PBRT versus WPRT. Levels of various metabolites were significantly altered during radiotherapy. Baseline α-diversity was not associated with any toxicity outcome. Based on the metabolic fingerprint, no natural clustering according to toxicity profile could be achieved. CONCLUSIONS:Radiation dose and treatment volume demonstrated limited effects on microbiome and metabolome fingerprints. In addition, no distinctive signature for toxicity status could be established. There is an ongoing need for toxicity risk stratification tools for diagnostic and therapeutic purposes, but the current evidence implies that the translation of metabolic and microbial biomarkers into routine clinical practice remains challenging.

AbstractBackgroundThe currently available treatment planning systems (TPSs) are neither designed nor intended for accurate dose calculations in nontarget regions. The aim of this work is to quantify the accuracy and reliability of nontarget doses calculated by a commercially available TPS.MethodsNontarget doses calculated by the collapsed cone (CC) (v5.2) algorithm implemented in the RayStation (v6) TPS were compared to measured values. Different scenarios were investigated, from simple static fields to intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment plans. Deviations and confidence limits (CLs) were calculated between results of calculations and measurements—applying both local (δ) and global (Δ) normalization—for various points of interest (POIs). Results were based on a single‐institution experience for one clinical test case (prostate) and evaluated against internationally accepted criteria.ResultsOverall, the TPS underestimated the nontarget dose by an average of −17.7% ± 25.3% for IMRT. Quantitatively similar results were obtained for VMAT (−17.6% ± 21.2%). POIs receiving < 5% of the prescription dose were significantly underestimated by the TPS (p‐value < 0.05 for both IMRT and VMAT). Dose calculation accuracy was also determined by the contribution of secondary radiation, with measured doses for out‐of‐field POIs being significantly different from calculated values (p‐value < 0.01 for both IMRT and VMAT). Although the CLδ in nontarget regions failed the proposed tolerance criteria (40%) for both IMRT (68.8%) and VMAT (52.6%), the CLΔ was within the tolerance limit (4%) for both treatment techniques (1.9% for IMRT and 1.3% for VMAT). No action levels (7%) were exceeded.ConclusionsBased on the currently available benchmarks our TPS is considered acceptable for clinical use, although the dose in some POIs was poorly predicted by the CC algorithm. Some areas were pointed out where TPSs and linear accelerator control systems can be improved.

Proton therapy is of great interest to pediatric cancer patients because of its optimal depth dose distribution. In view of healthy tissue damage and the increased risk of secondary cancers, we investigated DNA damage induction and repair of radiosensitive hematopoietic stem and progenitor cells (HSPCs) exposed to therapeutic proton and photon irradiation due to their role in radiation-induced leukemia. Human CD34+ HSPCs were exposed to 6 MV X-rays, mid- and distal spread-out Bragg peak (SOBP) protons at doses ranging from 0.5 to 2 Gy. Persistent chromosomal damage was assessed with the micronucleus assay, while DNA damage induction and repair were analyzed with the γ-H2AX foci assay. No differences were found in induction and disappearance of γ-H2AX foci between 6 MV X-rays, mid- and distal SOBP protons at 1 Gy. A significantly higher number of micronuclei was found for distal SOBP protons compared to 6 MV X-rays and mid- SOBP protons at 0.5 and 1 Gy, while no significant differences in micronuclei were found at 2 Gy. In HSPCs, mid-SOBP protons are as damaging as conventional X-rays. Distal SOBP protons showed a higher number of micronuclei in HSPCs depending on the radiation dose, indicating possible changes of the in vivo biological response.

Background: We investigated how radiotherapy (RT) parameters may contribute to the risk of lymphopenia in urological tumors and we discussed how this may impact clinical outcomes. Material & methods: A systematic review was performed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. The PubMed, Embase and ISI Web Of Knowledge databases were searched. Study quality was assessed according to the Newcastle-Ottawa Scale. Results: Overall, 8 articles reporting on a total of 549 urological cancer patients met the inclusion criteria. The pooled mean incidence of acute severe lymphopenia (absolute lymphocyte count < 500 cells/mu L) was 17.1%. Extended radiation volumes may lead to an increased risk of developing lymphopenia. Medium-high doses (>= 40 Gy) to the whole pelvic (odds ratio (OR) = 1.01; 95% confidence interval (CI) 1.001.01; p = 0.025) and iliac (OR = 1.04; 95% CI 1.01-1.08; p = 0.009) bone marrow (BM) were associated with acute grade 3 and late grade 2 lymphopenia, respectively. Conclusion: Multiple studies reported high and severe incidences of lymphopenia. Minimizing radiation volumes and unintentional irradiation of pelvic BM may reduce the incidence of lymphopenia, potentially improving clinical outcomes. More research is needed to further elucidate these findings and effectively implement recently developed new risk assessment tools. (c) 2022 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 170 (2022) 64-69

Background This study aimed to verify the dosimetric impact of Acuros XB (AXB) (AXB, Varian Medical Systems Palo Alto CA, USA), a two model-based algorithm, in comparison with Anisotropic Analytical Algorithm (AAA ) calculations for prostate, head and neck and lung cancer treatment by volumetric modulated arc therapy (VMAT ), without primary modification to AA. At present, the well-known and validated AA algorithm is clinically used in our department for VMAT treatments of different pathologies. AXB could replace it without extra measurements. The treatment result and accuracy of the dose delivered depend on the dose calculation algorithm. Materials and method Ninety-five complex VMAT plans for different pathologies were generated using the Eclipse version 15.0.4 treatment planning system (TPS). The dose distributions were calculated using AA and AXB (dose-to-water, AXBw and dose-to-medium, AXBm), with the same plan parameters for all VMAT plans. The dosimetric parameters were calculated for each planning target volume (PTV) and involved organs at risk (OA R). The patient specific quality assurance of all VMAT plans has been verified by Octavius®-4D phantom for different algorithms. Results The relative differences among AA, AXBw and AXBm, with respect to prostate, head and neck were less than 1% for PTV D95%. However, PTV D95% calculated by AA tended to be overestimated, with a relative dose difference of 3.23% in the case of lung treatment. The absolute mean values of the relative differences were 1.1 ± 1.2% and 2.0 ± 1.2%, when comparing between AXBw and AA, AXBm and AA, respectively. The gamma pass rate was observed to exceed 97.4% and 99.4% for the measured and calculated doses in most cases of the volumetric 3D analysis for AA and AXBm, respectively. Conclusion This study suggests that the dose calculated to medium using AXBm algorithm is better than AAA and it could be used clinically. Switching the dose calculation algorithm from AA to AXB does not require extra measurements.

Purpose: The study was performed comparing dosimetric characteristics of volumetric modulated arc therapy (VMAT) and field-in-field (FiF) techniques on a patient with synchronous bilateral breast carcinoma. Methods: The patients with bilateral breast cancer treatment were included in this study. A total dose of 40.05 Gy in 15 fractions was prescribed to the Planning Target Volume (PTV) of the whole bilateral breast cancer with the supraclavicular and infraclavicular nodes, with a complementary boost of 10 Gy in 4 fractions to the surgical bed (PTVboost). For both radiotherapy techniques, several VxGy parameters were analyzed for the PTVs, together with the Conformity index (CI), the Homogeneity index (HI) and the critical organs at risk (OARs), lungs and heart. Results: The patient was treated by the VMAT technique and the daily treatment time was less than 20 minutes with daily CBCT imaging. In the VMAT plan, the PTV 95% dose covered 38.89 ± 0.81 Gy, compared to 37.26 ± 1.02 Gy in the FiF technique. The VMAT plan improved the dose homogeneity index and lower dose in lung towards high dose region. Conclusion: The study demonstrates the viability of the VMAT technique in the treatment of bilateral breast cancer. The introduced single isocentric VMAT technique is fast to deliver and it increases the dose homogeneity of the target volume with some limitations. The treatment was well tolerated, without interruption of the treatment courses caused by treatment-related toxicities.

Background and purposeThe prognostic value of radiomics for non-small cell lung cancer (NSCLC) patients has been investigated for images acquired prior to treatment, but no prognostic model has been developed that includes the change of radiomic features during treatment. Therefore, the aim of this study was to investigate the potential added prognostic value of a longitudinal radiomics approach using cone-beam computed tomography (CBCT) for NSCLC patients.Materials and methodsThis retrospective study includes a training dataset of 141 stage I–IV NSCLC patients and three external validation datasets of 94, 61 and 41 patients, all treated with curative intended (chemo)radiotherapy. The change of radiomic features extracted from CBCT images was summarized as the slope of a linear regression. The CBCT slope-features and CT-extracted features were used as input for a Cox proportional hazards model. Moreover, prognostic performance of clinical parameters was investigated for overall survival and locoregional recurrence. Model performances were assessed using the Kaplan–Meier curves and c-index.ResultsThe radiomics model contained only CT-derived features and reached a c-index of 0.63 for overall survival and could be validated on the first validation dataset. No model for locoregional recurrence could be developed that validated on the validation datasets. The clinical parameters model could not be validated for either overall survival or locoregional recurrence.ConclusionIn this study we could not confirm our hypothesis that longitudinal CBCT-extracted radiomic features contribute to improved prognostic information. Moreover, performance of baseline radiomic features or clinical parameters was poor, probably affected by heterogeneity within and between datasets.

ConclusionBolus considerably improves the dose distribution in thin chest wall target.It is advisable also for other chest wall thicknesses to achieve better target coverage and decrease the overdose volume.Dose estimation in presence of bolus is more robust and less sensitive to the calculation algorithm.If the improved dose distribution with bolus translates into fewer chest wall recurrences needs to be verified in clinical trials.

S58 ESTRO 38available.It needs prescription at the right time.It has to be given at the right form.The whole of these elements are covered by the process of 'Quality Assurance' which is the responsibility of all bodies involved".I met Emmanuel vander Schueren early in my career on a European Quality network in RT meeting, he made an impact on me.Since then I have had a

Purpose In advanced radiotherapy techniques such as intensity-modulated radiation therapy (IMRT), the quality assurance (QA) process is essential. The aim of the study was to assure the treatment planning dose delivered during delivery of complex treatment plans. The QA standard is to perform patient-specific comparisons between planned doses and doses measured in a phantom. Materials and method The Delta 4 phantom (Scandidos, Uppsala, Sweden) has been used in this study. This device consists of diode matrices in two orthogonal planes inserted in a cylindrical acrylic phantom. Each diode is sampled per beam pulse so that the dose distribution can be evaluated on segment-by-segment, beam-by-beam, or as a composite plan from a single set of measurements. Ninety-five simple and complex radiotherapy treatment plans for different pathologies, planned using a treatment planning system (TPS) were delivered to the QA device. The planned and measured dose distributions were then compared and analysed. The gamma index was determined for different pathologies. Results The evaluation was performed in terms of dose deviation, distance to agreement and gamma index passing rate. The measurements were in excellent agreement between with the calculated dose of the TPS and the QA device. Overall, good agreement was observed between measured and calculated doses in most cases with gamma values above 1 in >95% of measured points. Plan results for each test met the recommended dose goals. Conclusion The delivery of IMRT and volumetric-modulated arc therapy (VMAT) plans was verified to correspond well with calculated dose distributions for different pathologies. We found the Delta 4 device is accurate and reproducible. Although Delta4 appears to be a straightforward device for measuring dose and allows measure in real-time dosimetry QA, it is a complex device and careful quality control is required before its use.

Purpose: Automated planning aims to speed up treatment planning and improve plan quality. We compared manual planning with automated planning for lung stereotactic body radiation therapy based on dose-volume histogram statistics and clinical preference. Methods and Materials: Manual and automated intensity modulated radiation therapy plans were generated for 56 patients by use of software developed in-house and Pinnacle 9.10 Auto-Planning, respectively. Optimization times were measured in 10 patients, and the impact of the automated plan (AP) on the total treatment cost was estimated. For the remaining 46 patients, each plan was checked against our clinical objectives, and a pair-wise dose-volume histogram comparison was performed. Three experienced radiation oncologists evaluated each plan and indicated their preference. Results: APs reduced the average optimization time by 77.3% but only affected the total treatment cost by 3.6%. Three APs and 0 manual plans failed our clinical objectives, and 13 APs and 9 manual plans showed a minor deviation. APs significantly reduced D2% (2% of the volume receives a dose of at least D2%) for the spinal cord, esophagus, heart, aorta, and main stem bronchus (P <.05) while preserving target coverage. The radiation oncologists found > 75% of the APs clinically acceptable without any further fine-tuning. Conclusions: APs may help to create satisfactory treatment plans quickly and effectively. Because critical appraisal by qualified professionals remains necessary, there is no such thing as "fully automated" planning yet. (C) 2018 Elsevier Inc. All rights reserved.

A central aspect of the RTNORM project is that experimental determinations and Monte Carlo calculations of kQ,Q0 factors are cross-validated internally in the project consortium prior to the submission of a consistent dataset to the IAEA Task Group for the update of the IAEA TRS-398.The RTNORM project aims at contributing towards this update by addressing the following objectives: 1. kV x-ray beams between 100 kV and 250 kV, targeting kQ,Q0 factors with a target standard uncertainty better than 1.0 %. 2. High-energy (MV) photon beams between 4 MV and 20 MV, including conventional flattening filter (cFF) and flattening filter free beams (FFF), targeting kQ,Q0 factors with a target standard uncertainty better than 0.7 %. 3. Scanned proton beams between 60 MeV and 250 MeV, targeting kQ,Q0 factors with a target standard uncertainty better than 2.0 %.