Assessment of four dose calculation algorithms using IAEA-TECDOC-1583 with medium dependency correction factor (Kmed) application.

PURPOSE: This study discusses the measurement of dose in clinical commissioning tests described in IAEA-TECDOC-1583. It explores the application of Monte Carlo (MC) modelled medium dependency correction factors (Kmed) for accurate dose measurement in bone and lung materials using the CIRS phantom. METHODS: BEAMnrc codes simulate radiation sources and model radiation transport for 6 MV and 15 MV photon beams. CT images of the CIRS phantom are converted to an MC compatible phantom. The PTW 30013 farmer chamber measures doses within modeled CIRS phantom. Kmed are determined by averaging values from four central voxels within the sensitive volume of the farmer chamber. Kmed is calculated for Dm.m and Dw.w algorithm types in bone and lung media for both photon beams. RESULTS: Average modelled correction factors for Dm.m calculations using the farmer chamber are 0.976 (±0.1 %) for 6 MV and 0.979 (±0.1 %) for 15 MV in bone media. Correspondingly, correction factors for Dw.w calculations are 0.99 (±0.3 %) and 0.992 (±0.4 %), respectively. For lung media, average correction factors for Dm.m calculations are 1.02 (±0.3 %) for 6 MV and 1.022 (±0.4 %) for 15 MV. Correspondingly, correction factors for Dw.w calculations are 1.01 (±0.3 %) and 1.012 (±0.2 %), respectively. CONCLUSIONS: This study highlights the significant impact of applying Kmed on dose differences between measurement and calculation during the dose audit process.

90Y post-radioembolization clinical assessment with whole-body Biograph Vision Quadra PET/CT: image quality, tumor, liver and lung dosimetry.

PURPOSE: Evaluation of 90Y liver radioembolization post-treatment clinical data using a whole-body Biograph Vision Quadra PET/CT to investigate the potential of protocol optimization in terms of scan time and dosimetry. METHODS: 17 patients with hepatocellular carcinoma with median (IQR) injected activity 2393 (1348-3298) MBq were included. Pre-treatment dosimetry plan was based on 99mTc-MAA SPECT/CT with Simplicit90Y™ and post-treatment validation with Quadra using Simplicit90Y™ and HERMIA independently. Regarding the image analysis, mean and peak SNR, the coefficient of variation (COV) and lesion-to-background ratio (LBR) were evaluated. For the post-treatment dosimetry validation, the mean tumor, whole liver and lung absorbed dose evaluation was performed using Simplicit90Y and HERMES. Images were reconstructed with 20-, 15-, 10-, 5- and 1- min sinograms with 2, 4, 6 and 8 iterations. Wilcoxon signed rank test was used to show statistical significance (p < 0.05). RESULTS: There was no difference of statistical significance between 20- and 5- min reconstructed times for the peak SNR, COV and LBR. In addition, there was no difference of statistical significance between 20- and 1- min reconstructed times for all dosimetry metrics. Lung dosimetry showed consistently lower values than the expected. Tumor absorbed dose based on Simplicit90Y™ was similar to the expected while HERMES consistently underestimated significantly the measured tumor absorbed dose. Finally, there was no difference of statistical significance between expected and measured tumor, whole liver and lung dose for all reconstruction times. CONCLUSION: In this study we evaluated, in terms of image quality and dosimetry, whole-body PET clinical images of patients after having been treated with 90Y microspheres radioembolization for liver cancer. Compared to the 20-min standard scan, the simulated 5-min reconstructed images provided equal image peak SNR and noise behavior, while performing also similarly for post-treatment dosimetry of tumor, whole liver and lung absorbed doses.

Quantitative Assessment and Comparative Analysis of Longitudinal Lung CT Scans of Chest-Irradiated Nonhuman Primates.

Computed tomography (CT) imaging has been used to diagnose radiation-induced lung injury for decades. However, histogram-based quantitative tools have rarely been applied to assess lung abnormality due to radiation-induced lung injury (RILI). Here, we used first-order summary statistics to derive and assess threshold measures extracted from whole lung histograms of CT radiodensity in rhesus macaques. For the present study, CT scans of animals exposed to 10 Gy of whole thorax irradiation were utilized from a previous study spanning 2-9 months postirradiation. These animals were grouped into survivors and non-survivors based on their clinical and experimental endpoints. We quantified the change in lung attenuation after irradiation relative to baseline using three density parameters; average lung density (ALD), percent change in hyper-dense lung volume (PCHV), hyperdense volume as a percent of total volume (PCHV/TV) at 2-month intervals and compared each parameter between the two irradiated groups (non-survivors and survivors). We also correlated our results with histological findings. All the three indices (ALD, PCHV, PCHV/TV) obtained from density histograms showed a significant increase in lung injury in non-survivors relative to survivors, with PCHV relatively more sensitive to detect early RILI changes. We observed a significant positive correlation between histologic pneumonitis scores and each of the three CT measurements, indicating that CT density is useful as a surrogate for histologic disease severity in RILI. CT-based three density parameters, ALD, PCHV, PCHV/TV, may serve as surrogates for likely histopathology patterns in future studies of RILI disease progression.

Magnetic-field-modulated radiotherapy (MagMRT) in inhomogeneous medium and its potential applications.

Objective.To study the effects of magnetic field gradients on the dose deposition in an inhomogeneous medium and to present the benefits offered by magnetic-field-modulated radiotherapy (MagMRT) under multiple radiation beams.Approach.Monte Carlo simulations were performed using the Geant4 simulation toolkit with a 7 MV photon beam from an Elekta Unity system. A water cuboid embedded with material slabs of water, bone, lung or air was used to study the effects of MagMRT within inhomogeneous medium. Two cylindrical water phantoms, with and without a toroidal lung insert embedded, were used to study the effects of MagMRT under single, opposing or four cardinal radiation beams. Optimized magnetic field variations in the form of a wavelet were used to induce dose modulation within the material slabs or at the iso-center of the phantoms.Main results.The magnitudes of the dose enhancement and reduction induced by the magnetic field gradients become more prominent in a medium of lower density. A maximum dose increase of 6.5% and a decrease of 4.8% were found inside bone, while an increase of 20.4% and a decrease of 13.9% were found in lung tissue. Under multiple radiation beams, the dose enhancement can be induced at the iso-center while the dose reduction occurs in regions around the tumor. For the case with four cardinal beams irradiating a homogeneous water cylinder, an 8.4% of dose enhancement and a 2.4% of dose reduction were found. When a toroidal lung insert was embedded, a maximum dose enhancement of 9.5% and a reduction of 17.0% were produced for anterior-posterior opposing fields.Significance.With an optimized magnetic field gradient, MagMRT can induce a dose boost to the target while producing a better sparing to the surrounding normal tissue, resulting in a sharper dose fall-off in all directions outside the target volume.

Development of a scatter correction technique for planar 99mTc-MAA imaging to improve accuracy in lung shunt fraction estimation.

PURPOSE: Prior to 90Y selective internal radiation therapy (SIRT) treatment, 99mTc-MAA scintigraphy imaging is used in the estimation of the lung shunt fraction (LSF). Planar imaging is recommended for determining a LSF ratio. However, the estimate may be affected by scatter contributions, attenuation and respiratory motion. The objective of this study was to correct for the effects of scatter in the LSF, towards the determination of a more accurate estimation method of LSF derived from planar scintigraphy imaging, which is recommended by international guidelines. METHODS: The open access SIMIND Monte Carlo modelling software was used to estimate an optimum scatter window (SW) for scatter correction. The uncertainties associated with scatter and scatter contributions from the liver on the LSF were evaluated using an anthropomorphic thorax phantom and a virtual Vox-Man phantom. A brief retrospective examination of patient scans and tumour location investigated the impact that the inclusion of the simulated scatter corrections had on the LSF estimation. RESULTS: The percentage overestimation of the manufacturer recommended method of LSF estimation was 192%. SW corrections improved the uncertainty to within 19% for the range of known LSFs. Similar findings were observed for our patient and tumour location studies. CONCLUSION: The incorporated scatter corrections can significantly improve the accuracy of the LSF estimation, thereby providing a robust gamma camera, patient and tumour depth specific correction which is easily implementable. This is supported by Monte Carlo, phantom and preliminary patient studies.

Multi-scaled Monte Carlo calculation for radon-induced cellular damage in the bronchial airway epithelium.

Radon is a leading cause of lung cancer in indoor public and mining workers. Inhaled radon progeny releases alpha particles, which can damage cells in the airway epithelium. The extent and complexity of cellular damage vary depending on the alpha particle's kinetic energy and cell characteristics. We developed a framework to quantitate the cellular damage on the nanometer and micrometer scales at different intensities of exposure to radon progenies Po-218 and Po-214. Energy depositions along the tracks of alpha particles that were slowing down were simulated on a nanometer scale using the Monte Carlo code Geant4-DNA. The nano-scaled track histories in a 5 µm radius and 1 µm-thick cylindrical volume were integrated into the tracking scheme of alpha trajectories in a micron-scale bronchial epithelium segment in the user-written SNU-CDS program. Damage distribution in cellular DNA was estimated for six cell types in the epithelium. Deep-sited cell nuclei in the epithelium would have less chance of being hit, but DNA damage from a single hit would be more serious, because low-energy alpha particles of high LET would hit the nuclei. The greater damage in deep-sited nuclei was due to the 7.69 MeV alpha particles emitted from Po-214. From daily work under 1 WL of radon concentration, basal cells would respond with the highest portion of complex DSBs among the suspected progenitor cells in the most exposed regions of the lung epithelium.

Monte Carlo simulation of enriched uranium in the lungs of thorax voxel phantom for assessment of enrichment and its effect on dose.

In-vivo lung monitoring is an important technique for the assessment of internal dose of radiation workers handling actinides. At BARC, counting efficiencies (CEs) of detection systems used for estimation of natural uranium in the lungs are evaluated using realistic thorax physical phantoms or computational voxel phantoms. The quantification of 238U and 235U in lungs is done using CEs determined at 63.3 keV and 185.7 keV photon energies respectively. These CEs can also be used for assessment of enriched uranium in the lungs of the workers. In this study, spectra are generated for HPGe array detectors using Monte Carlo simulations of various enriched uranium compositions distributed in the lungs of thorax voxel phantom. A methodology is developed to predict the 235U enrichment from lung spectrum analysis using the ratio of net counts in 185.7 keV and 63.3 keV energy regions. It is possible to estimate enrichments in the range of 2%-30% using the developed method with less than ±9% error. Finally, effect of 235U enrichment on dose assessment using lung monitoring method is studied.

The Theoretical Value of Whole-Lung Irradiation for COVID-19 Pneumonia: A Reasonable and Safe Solution until Targeted Treatments are Developed.

In this work, we considered the theoretical role of low-dose radiation therapy (approximately 0.5-1.0 Gy) in the treatment of respiratory distress syndrome associated with COVID-19 infection. Monte Carlo calculations were performed to gauge the ability to deliver low-dose radiation to the thoracic mid-plane using an orthovoltage machine. In addition, the potential harm of a single dose of 0.75 Gy (whole-lung irradiation) was assessed based on the recommendations of the BEIR-VII committee of the U.S. National Research Council. Based on the results of this work, it was determined that an orthovoltage machine (minimum 300 kVp) can be used to deliver 0.75 Gy dose to the lungs while respecting cutaneous tolerance. Using data from the BEIR-VII Committee, it is evident that the apparent benefits of such radiation treatment for patients suffering from severe manifestations of the COVID-19 infectious syndrome outweigh the potential loss of life due to radiation-induced malignancy. Although the vaccination against COVID-19 has become a reality, the spread and mortality in severely ill patients remain unacceptably high. The risk of outbreaks in the future is unknown. We suggest herein that low-dose radiotherapy at the bedside should be rigorously considered as a therapeutic option since it appears to be feasible and safe in the short and long term.

Ipsilateral lung normal tissue complication probability parameters for different dose calculation algorithms in radiotherapy of breast cancer.

PURPOSE: Different dose calculation algorithms (DCAs) predict different dose distributions for the same treatment. Awareness of optimal model parameters is vital for estimating normal tissue complication probability (NTCP) for different algorithms. The aim is to determine the NTCP parameter values for different DCAs in left-sided breast radiotherapy, using the Lyman-Kutcher-Burman (LKB) model. MATERIALS AND METHODS: First, the methodology recommended by International Atomic Energy Agency TEC-DOC 1583 was used to establish the accuracy of dose calculations of different DCAs including: Monte Carlo (MC) and collapsed cone algorithms implemented in Monaco, pencil beam convolution (PBC) and analytical anisotropic algorithm (AAA) implemented in Eclipse, and superposition and Clarkson algorithms implemented in PCRT3D treatment planning systems (TPSs). Then, treatment planning of 15 patients with left-sided breast cancer was performed by the mentioned DCAs and NTCP of the left-lung normal tissue were calculated for each patient individually, using the LKB model. For the PB algorithm, the NTCP parameters were taken from previously published values and new model parameters obtained for each DCA, using the iterative least squares methods. RESULTS: For all cases and DCAs, NTCP computation with the same model parameters resulted in >15% deviation in NTCP values. The new NTCP model parameters were classified according to the algorithm type. Thus, the discrepancy of NTCP computations was reduced up to 5% after utilizing adjusted model parameters. CONCLUSIONS: This paper confirms that the NTCP values for a given treatment type are different for the different DCAs. Thus, it is essential to introduce appropriate NTCP parameter values according to DCA adopted in TPS, to obtain a more precise estimation of lung NTCP. Hence, new parameter values, classified according to the DCAs, must be determined before introducing NTCP estimation in clinical practice.

Monte Carlo 90Y PET/CT dosimetry of unexpected focal radiation-induced lung damage after hepatic radioembolisation.

Transarterial radioembolization (TARE) with 90Y-loaded microspheres is an established therapeutic option for inoperable hepatic tumors. Increasing knowledge regarding TARE hepatic dose-response and dose-toxicity correlation is available but few studies have investigated dose-toxicity correlation in extra-hepatic tissues. We investigated absorbed dose levels for the appearance of focal lung damage in a case of off-target deposition of 90Y microspheres and compared them with the corresponding thresholds recommended to avoiding radiation induced lung injury following TARE. A 64-year-old male patient received 1.6 GBq of 90Y-labelled glass microspheres for an inoperable left lobe hepatocellular carcinoma. A focal off-target accumulation of radiolabeled microspheres was detected in the left lung upper lobe at the post-treatment 90Y-PET/CT, corresponding to a radiation-induced inflammatory lung lesion at the 3-months 18F-FDG PET/CT follow-up. 90Y-PET/CT data were used as input for Monte-Carlo based absorbed dose estimations. Dose-volume-histograms were computed to characterize the heterogeneity of absorbed dose distribution. The dose level associated with the appearance of lung tissue damage was estimated as the median absorbed dose measured at the edge of the inflammatory nodule. To account for respiratory movements and possible inaccuracy of image co-registration, three different methods were evaluated to define the irradiated off-target volume. Monte Carlo-derived absorbed dose distribution showed a highly heterogeneous absorbed dose pattern at the site of incidental microsphere deposition (volume = 2.13 ml) with a maximum dose of 630 Gy. Absorbed dose levels ranging from 119 Gy to 133 Gy, were estimated at the edge of the inflammatory nodule, depending on the procedure used to define the target volume. This report describes an original Monte Carlo based patient-specific dosimetry methodology for the study of the radiation-induced damage in a focal lung lesion after TARE. In our patient, radiation-induced focal lung damage occurred at significantly higher absorbed doses than those considered for single administration or cumulative lung dose delivered during TARE.

Monte Carlo simulation of the effect of magnetic fields on brachytherapy dose distributions in lung tissue material.

The aim of this work was to use TOPAS Monte Carlo simulations to model the effect of magnetic fields on dose distributions in brachytherapy lung treatments, under ideal and clinical conditions. Idealistic studies were modeled consisting of either a monoenergetic electron source of 432 keV, or a polyenergetic electron source using the spectrum of secondary electrons produced by 192Ir gamma-ray irradiation. The electron source was positioned in the center of a homogeneous, lung tissue phantom (ρ = 0.26 g/cm3). Conversely, the clinical study was simulated using the VariSource VS2000 192Ir source in a patient with a lung tumor. Three contoured volumes were considered: the tumor, the planning tumor volume (PTV), and the lung. In all studies, dose distributions were calculated in the presence or absence of a constant magnetic field of 3T. Also, TG-43 parameters were calculated for the VariSource and compared with published data from EGS-brachy (EGSnrc) and PENELOPE. The magnetic field affected the dose distributions in the idealistic studies. For the monoenergetic and poly-energetic studies, the radial distance of the 10% iso-dose line was reduced in the presence of the magnetic field by 64.9% and 24.6%, respectively. For the clinical study, the magnetic field caused differences of 10% on average in the patient dose distributions. Nevertheless, differences in dose-volume histograms were below 2%. Finally, for TG-43 parameters, the dose-rate constant from TOPAS differed by 0.09% ± 0.33% and 0.18% ± 0.33% with respect to EGS-brachy and PENELOPE, respectively. The geometry and anisotropy functions differed within 1.2% ± 1.1%, and within 0.0% ± 0.3%, respectively. The Lorentz forces inside a 3T magnetic resonance machine during 192Ir brachytherapy treatment of the lung are not large enough to affect the tumor dose distributions significantly, as expected. Nevertheless, large local differences were found in the lung tissue. Applications of this effect are therefore limited by the fact that meaningful differences appeared only in regions containing air, which is not abundant inside the human.

Simulation and measurement of microbeam dose distribution in lung tissue.

Microbeam radiation therapy (MRT), a so far preclinical method in radiation oncology, modulates treatment doses on a micrometre scale. MRT uses treatment fields with a few ten micrometre wide high dose regions (peaks) separated by a few hundred micrometre wide low dose regions (valleys) and was shown to spare tissue much more effectively than conventional radiation therapy at similar tumour control rates. While preclinical research focused primarily on tumours of the central nervous system, recently also lung tumours have been suggested as a potential target for MRT. This study investigates the effect of the lung microstructure, comprising air cavities of a few hundred micrometre diameter, on the microbeam dose distribution in lung. In Monte Carlo simulations different models of heterogeneous lung tissue are compared with pure water and homogeneous air-water mixtures. Experimentally, microbeam dose distributions in porous foam material with cavity sizes similar to the size of lung alveoli were measured with film dosimetry at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Simulations and experiments show that the microstructure of the lung has a huge impact on the local doses in the microbeam fields. Locally, material inhomogeneities may change the dose by a factor of 1.7, and also average peak and valley doses substantially differ from those in homogeneous material. Our results imply that accurate dose prediction for MRT in lung requires adequate models of the lung microstructure. Even if only average peak and valley doses are of interest, the assumption of a simple homogeneous air-water mixture is not sufficient. Since anatomic information on a micrometre scale are unavailable for clinical treatment planning, alternative methods and models have to be developed.

Low dose lung radiation therapy for pneumonia: an examination of historical dose distributions.

The novel coronavirus, SARS-CoV-2, that causes the COVID-19 disease currently has healthcare systems around the world dealing with unprecedented numbers of critically ill patients. One of the primary concerns associated with this illness is acute respiratory distress syndrome (ARDS) and the pneumonia that accompanies it. Historical literature dating back to the 1940s and earlier contains many reports of successful treatment of pneumonias with ionizing radiation. Although these were not randomized controlled trials, they do suggest a potential avenue for further investigation. Technical details in these reports however were limited. In this work we review the literature and identify details including nominal kilovoltage ranges, filtration, and focus-skin distances (FSDs). Using a freely available and benchmarked code, we generated spectra and used these as sources for Monte Carlo simulations using the EGSnrc software package. The approximate sources were projected through a radiologically anthropomorphic phantom to provide detailed dose distributions within a targeted lung volume (approximate right middle lobe). After accounting for the reported exposure levels, mean lung doses fell in a relatively narrow range: 30-80 cGy. Variation in patient dimensions and other details are expected to result in an uncertainty on the order of ± 20%. This result is consistent with the dose range expected to induce anti-inflammatory effects.

Monte-Carlo-computed dose, kerma and fluence distributions in heterogeneous slab geometries irradiated by small megavoltage photon fields.

Small-field dosimetry is central to the planning and delivery of radiotherapy to patients with cancer. Small-field dosimetry is beset by complex issues, such as loss of charged-particle equilibrium (CPE), source occlusion and electron-scattering effects in low-density tissues. The purpose of the present research is the elucidation of the fundamental physics of small fields through the computation of absorbed dose, kerma and fluence distributions in heterogeneous media using the Monte-Carlo (MC) method. Absorbed dose and kerma were computed using the DOSRZnrc MC user-code for beams with square field sizes ranging from 0.25 × 0.25 to 7 × 7 cm2 (for 6 MV 'full linac' geometry) and 0.25 × 0.25 to 16 × 16 cm2 (for 15 MV 'full linac' geometry). In the bone inhomogeneity the dose increases (vs. homogeneous water) for field sizes <1 × 1 cm2 at 6 MV and ⩽3 × 3 cm2 at 15 MV and decreases (vs. homogeneous water) for field sizes ⩾3 × 3 cm2 at 6 MV and ⩾5 × 5 cm2 at 15 MV. In the lung inhomogeneity there is negligible decrease in dose compared to in uniform water for field sizes >5 × 5 cm2 at 6 MV and ⩾16 × 16 cm2 at 15 MV, consistent with the Fano theorem. The near-unity value of the absorbed-dose to collision-kerma ratio, D/K col, at the centre of the bone and lung slabs in the heterogeneous phantom demonstrates that CPE is achieved in bone for field sizes >1 × 1 cm2 at 6 MV and ⩾5 × 5 cm2 at 15 MV; CPE is achieved in lung at field sizes >5 × 5 cm2 at 6 MV and ⩾16 × 16 cm2 at 15 MV. Electron-fluence perturbation factors for the 0.25 × 0.25 cm2 field were 1.231 and 1.403 for bone-to-water and 0.454 and 0.333 for lung-to-water at 6 and 15 MV, respectively. For field sizes large enough for quasi-CPE, the MC-derived dose-perturbation factors, lung-to-water, [Formula: see text] were close to unity; electron-fluence perturbation factors, lung-to-water, [Formula: see text] were ∼1.0, consistent with the Fano theorem. At 15 MV in the lung inhomogeneity the magnitude and also the 'shape' of the primary electron-fluence spectrum differ significantly from that in water. Beam penumbrae relative to water are narrower in the bone inhomogeneity and broader in the lung inhomogeneity for all field sizes.

Radiological assessment after stereotactic body radiation of lung tumours.

The increasing use of stereotactic body radiation therapy for lung tumours comes along with new post-therapeutic imaging findings that should be known by physicians involved in patient follow-up. Radiation-induced lung injury is much more frequent than after conventional radiation therapy, it can also be delayed and has a different radiological presentation. Radiation-induced lung injury after stereotactic body radiation therapy involves the lung parenchyma surrounding the target tumour and appears as a dynamic process continuing for years after completion of the treatment. Thus, the radiological pattern and the severity of radiation-induced lung injury are prone to changes during follow-up, which can make it difficult to differentiate from local recurrence. Contrary to radiation-induced lung injury, local recurrence after stereotactic body radiation therapy is rare. Other complications mainly depend on tumour location and include airway complications, rib fractures and organizing pneumonia. The aim of this article is to provide a wide overview of radiological changes occurring after SBRT for lung tumours. Awareness of changes following stereotactic body radiation therapy should help avoiding unnecessary interventions for pseudo tumoral presentations.

An Assessment of Radiation Doses From Radon Exposures Using a Mouse Model System.

BACKGROUND: Radon and its progenies contribute significantly to the natural background radiation and cause several thousands of lung cancer cases per year worldwide. Moreover, patients with chronic inflammatory joint diseases are treated in radon galleries. Due to the complex nature of radon exposure, the doses associated with radon exposures are difficult to assess. Hence, there is a clear need to directly measure dose depositions from radon exposures to provide reliable risk estimates for radiation protection guidelines. OBJECTIVES: We aimed to assess tissue-specific radiation doses associated with radon activity concentrations, that deposit similar dose levels as the annual natural radon exposure or radon gallery visits. METHODS: We exposed mice to defined radon concentrations, quantified the number of 53BP1 foci as a measure of induced DNA damage, and compared it with the number of foci induced by known doses of reference-type radiations. An image-based analysis of the 3-dimensional foci pattern provided information about the radiation type inflicting the DNA damage. RESULTS: A 1-hour exposure to 440 kBq/m3 radon-induced DNA damage corresponding to a dose of ∼10 mGy in the lung and ∼3.3 mGy in the kidney, heart, and liver. A 1-hour exposure to 44 kBq/m3 provided values consistent with a linear relationship between dose and radon concentration. Two-thirds of the dose in the lung was caused by α-particles. The dose in the kidney, heart, and liver and one-third of the dose in the lung likely resulted from ß- and γ-rays. DISCUSSION: We found that radon exposures mainly lead to α-particle-induced DNA damage in the lung, consistent with the lung cancer risk obtained in epidemiologic studies. Our presented biodosimetric approach can be used to benchmark risk model calculations for radiation protection guidelines and can help to understand the therapeutic success of radon gallery treatments.

Assessment of Genotoxicity in Human Cells Exposed to Modulated Electromagnetic Fields of Wireless Communication Devices.

Modulated electromagnetic fields (wEMFs), as generated by modern communication technologies, have raised concerns about adverse health effects. The International Agency for Research on Cancer (IARC) classifies them as "possibly carcinogenic to humans" (Group 2B), yet, the underlying molecular mechanisms initiating and promoting tumorigenesis remain elusive. Here, we comprehensively assess the impact of technologically relevant wEMF modulations on the genome integrity of cultured human cells, investigating cell type-specificities as well as time- and dose-dependencies. Classical and advanced methodologies of genetic toxicology and DNA repair were applied, and key experiments were performed in two separate laboratories. Overall, we found no conclusive evidence for an induction of DNA damage nor for alterations of the DNA repair capacity in cells exposed to several wEMF modulations (i.e., GSM, UMTS, WiFi, and RFID). Previously reported observations of increased DNA damage after exposure of cells to GSM-modulated signals could not be reproduced. Experimental variables, presumably underlying the discrepant observations, were investigated and are discussed. On the basis of our data, we conclude that the possible carcinogenicity of wEMF modulations cannot be explained by an effect on genome integrity through direct DNA damage. However, we cannot exclude non-genotoxic, indirect, or secondary effects of wEMF exposure that may promote tumorigenesis in other ways.

External beam patient dose verification based on the integral quality monitor (IQM®) output signals.

BACKGROUND: The Integral Quality Monitor (IQM®) can essentially measure the integral fluence through a segment and provide real-time information about the accuracy of radiation delivery based on comparisons of measured segment signals and pre-calculated reference values. However, the present IQM chamber cannot calculate the dose in the patient. AIM: This study aims to make use of IQM field output signals to calculate the number of monitor units (MUs) delivered through an arbitrary treatment field in order to convert Monte Carlo (MC)-generated dose distributions in a patient model into absolute dose. METHODS: XiO and Monaco treatment planning systems (TPSs) were used to define treatment beam portals for cervix and esophagus conformal radiotherapy as well as prostate intensity-modulated radiotherapy for the translation of patient and beam setup information from DICOM to DOSXYZnrc. The planned beams were simulated in a patient model built from actual patient CT images and each simulated integral field/segment was weighted with its MUs before summation to get the total dose in the plan. The segment beam weights (MUs) were calculated as the ratio of the open-field IQM measured signal and the calculated signal per MU extracted from chamber sensitivity maps. These are the actual MUs delivered not just MUs set. The beam weighting method was evaluated by comparing weighted MC doses with original planned doses using profile and isodose comparisons, dose difference maps, γ analysis and dose-volume histogram (DVH) data. RESULTS: γ pass rates of up to 98% were found, except for the esophagus plan where the γ pass rate was below 45%. DVH comparisons showed good agreement for most organs, with the largest differences observed in low-density lung. However, these discrepancies can result from differences in dose calculation algorithms or differences in MUs used for dose weighting planned by the TPS and MUs calculated using IQM field output signals. To test this, a 4-field box DOSXYZnrc MC simulation weighted with planned (XiO) MUs was compared with the same simulation weighted with IQM-based MUs. Dose differences of up to 5% were found on the isocentre slice. For XiO versus MC, up to 7% dose differences were found, indicating additional error due to limitations of XiO's superposition algorithm. Dose differences between MC Monaco and MC EGSnrc were less than 3%. CONCLUSIONS: The most valuable comparison was MC versus MC as it eliminated algorithm discrepancies and evaluated dose differences precisely according to beam weighting. For XiO TPS, care must be taken as dose differences may also arise due to limitations in XiO's planning software, not merely due to differences in MUs. Overall, the IQM was successfully used to compute beam dose weights to accurately reconstruct the patient dose using unweighted MC beams. Our technique can be used for pre-treatment QA provided each segment output is known and an accurate linac source model is available.

RETROSPECTIVE ASSESSMENT OF CLINICAL-MORPHOLOGICAL CHANGES OF THE HEPATOBILIARY SYSTEM IN LIVER CIRRHOSIS OF THE CHORNOBYL NPP ACCIDENT CLEAN-UP WORKERS. / RETROSPEKTYVNA OTsINKA KLINIKO-MORFOLOGIChNYKh ZMIN GEPATOBILIARNOÏ SYSTEMY PRY TsYROZI PEChINKY V UChASNYKIV LIKVIDATsIÏ NASLIDKIV ChORNOBYL'S'KOÏ KATASTROFY.

OBJECTIVE: to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident. MATERIALS AND METHODS: Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated. RESULTS: A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %. CONCLUSION: Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment.

Ionizing Radiation Promotes Epithelial-to-Mesenchymal Transition in Lung Epithelial Cells by TGF-ß-producing M2 Macrophages.

BACKGROUND/AIM: Ionizing radiation induces pulmonary fibrosis, which is a common dose-limiting complication in patients receiving radiotherapy. Fibrosis occurs through the accumulation of large amounts of ECM components, synthesized by myofibroblasts in damaged lung tissue. Epithelial cells serve as one of the cellular sources of myofibroblasts via the epithelial-to-mesenchymal transition (EMT) process. In this study, we investigated the role of TGF-ß-secreting M2 macrophages in association with ionizing radiation-induced EMT. MATERIALS AND METHODS: The lung epithelial cell line MLE12, was irradiated and the expression of EMT markers and chemokines was examined. Moreover, the mouse lung macrophage MH-S cell line was cultured with conditioned media from irradiated MLE12 cells, to examine the effects of the secreted factors on the migration ability of macrophages. For the murine pulmonary fibrosis model, mice were locally irradiated and the levels of M1 or M2 macrophage-related markers and cytokines were measured in bronchoalvelolar lavage (BAL) fluid and lung tissue. RESULTS: In MLE12 cells, irradiation directly induced expression of EMT-related markers and secretion of various chemokines, which lead to macrophage migration. Interestingly, the sub-population of macrophages recruited in the lung of mice after thoracic irradiation was M2 macrophages that expressed Arg-1 and CD206. M2 macrophages induced the MLE12 to undergo phenotypic conversion to form fibroblast-like cells, which leads to a down-regulation of epithelial markers and an up-regulation of new EMT-related markers. In thoracic irradiated mice, pro-inflammatory cytokines such as IL-1ß, IL-4 and IL-10 were increased at 2 weeks, but returned to normal levels from 16 weeks or 24 weeks after irradiation. However, thoracic irradiation led to a rapid increase of TGF-ß and IGF-1 levels, which lasted up to 24 weeks. It was confirmed that M2 macrophages secreted the high levels of TGF-ß. Moreover, the elimination of TGF-ß from M2 macrophages attenuated mesenchymal transition of MLE12. CONCLUSION: TGF-ß-secreting M2 macrophages play an important regulatory role in mesenchymal transition of epithelial cells in the lung of irradiated mice, thus contributing to radiation-induced pulmonary fibrosis.