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Purpose The purpose of this project was to assess factors that may influence variability in the pre-treatment kilovoltage cone beam computed tomography (kV CBCT) image matching process for lung stereotactic body radiation therapy (SBRT). Methods and materials Pre-treatment CBCT and planning CT data sets of previously-treated lung SBRT patients were gathered and anonymized from four radiotherapy centers in Alberta. Eight radiation therapists (RTTs) and four radiation oncologists (ROs) were recruited from the same four cancer centers for image matching. Identical data sets were provided to each user, but the order of image sets was randomized independently for each user to remove any learning bias. Inter-user variabilities were then investigated as functions of various factors, including image origin (source institution/machine), user's institution (local matching protocol), profession (RTT vs. RO), years of experience and image quality (presence/absence of added noise). Results Very little variation in image matching between different users was observed. The mean differences from the consensus means for different image sets were less than 1 mm in all directions, and cases that exceeded 3 mm (i.e. clinically significant differences) were extremely rare. Image origin, user's institution, and profession (RTT vs. RO) didn't lead to any meaningful clinical differences, while image quality didn't introduce any statistically significant differences. In addition, no discernible trend was seen between user's experience and deviation from the user mean. Overall, no meaningful differences in inter-user variabilities for the different factors investigated were found in this study. Conclusions There appears to be an adequate standardization across the province of Alberta in terms of CBCT image matching process. No clinically significant differences were observed as functions of various factors investigated in this study. Consistency in matching between RTTs and ROs in this study suggests that RTTs do not need systematic RO approval of their lung CBCT match. It should be noted that RTTs at the centers in this study receive comprehensive training in CBCT-based image matching.

Purpose: In recent years, much effort has been focused on developing new strategies for the prevention and mitigation of adverse radiation effects on healthy tissues and organs, including the brain. The brain is very sensitive to radiation effects, albeit as it is highly plastic. Hence, deleterious radiation effects may be potentially reversible. Because radiation exposure affects dendritic space, reduces the brain’s ability to produce new neurons, and alters behavior, mitigation efforts should focus on restoring these parameters. To that effect, environmental enrichment through complex housing (CH) and exercise may provide a plausible avenue for exploration of protection from brain irradiation. CH is a much broader concept than exercise alone, and constitutes exposure of animals to positive physical and social stimulation that is superior to their routine housing and care conditions. We hypothesized that CHs may lessen harmful neuroanatomical and behavioural effects of low dose radiation exposure. Methods: We analyzed and compared cerebral morphology in animals exposed to low dose head, bystander (liver), and scatter irradiation on rats housed in either the environmental enrichment condos or standard housing. Results: Enriched condo conditions ameliorated radiation-induced neuroanatomical changes. Moreover, irradiated animals that were kept in enriched CH condos displayed fewer radiation-induced behavioural deficits than those housed in standard conditions. Conclusions: Animal model-based environmental enrichment strategies, such as CH, are excellent surrogate models for occupational and exercise therapy in humans, and consequently have significant translational possibility. Our study may thus serve as a roadmap for the development of new, easy, safe and cost-effective methods to prevent and mitigate low-dose radiation effects on the brain.

This study quantified plan quality differences across the 4 cancer centers in Alberta, Canada for plans that followed the PROstate Fractionated Irradiation Trial protocol.Prostate plans of 235 patients were retrospectively reviewed. Interinstitutional plan quality comparisons were made based on distributions of protocol-specified parameters using 1-way analysis of variance with Games-Howell post hoc analysis. Dosimetrically representative cases were selected from each center using k-medoid clustering, enabling side-by-side comparison of dose-volume histograms and dose distributions. Fourteen anatomic features were investigated to explore interinstitutional patient population differences. Anatomically representative cases were selected from each center to explore differences in planning practices. Tumor control probability (TCP), as well as rectal wall and bladder wall normal tissue complication probabilities (NTCPs), were calculated to quantify the clinical effect of the differences in plan quality.Comparing the mean value of each center to the other 3, statistically significant differences were observed for bladder wall D30% and D50%, left and right femoral heads D5%, planning target volume D99% and D1cc, and clinical target volume D99%. Dosimetrically representative cases demonstrated consistent results. Although anatomic differences were observed between the center-specific populations, an analysis using anatomically similar cases demonstrated consistent trends in the dosimetric differences, suggesting the dosimetric variation is not exclusively due to anatomic differences. Minimal differences (1%) among the 4 centers were noted for TCP and NTCPs, suggesting the reported differences in plan quality may not have any clinical significance.Despite common guidelines, statistically significant differences in plan quality metrics occurred among the 4 investigated centers. The differences are due at least in part to variation in local planning practices. TCP and NTCP calculations suggest that the clinical significance of the differences is minimal. These results can serve as a reference for the degree of variation among centers that can be accepted when a common protocol is adopted.

Low dose radiation therapy (LDRT) using doses in the range of 30–150 cGy has been proposed as a means of mitigating the pneumonia associated with COVID-19. However, preliminary results from ongoing clinical trials have been mixed. The aim of this work is to develop a mathematical model of the viral infection and associated systemic inflammation in a patient based on the time evolution of the viral load. The model further proposes an immunomodulatory response to LDRT based on available data. Inflammation kinetics are then explored and compared to clinical results. The time evolution of a viral infection, inflammatory signaling factors, and inflammatory response are modeled by a set of coupled differential equations. Adjustable parameters are taken from the literature where available and otherwise iteratively adjusted to fit relevant data. Simple functions modeling both the suppression of pro-inflammatory signal factors and the enhancement of anti-inflammatory factors in response to low doses of radiation are developed. The inflammation response is benchmarked against C-reactive protein (CRP) levels measured for cohorts of patients with severe COVID-19. The model fit the time-evolution of viral load data, cytokine data, and inflammation (CRP) data. When LDRT was applied early, the model predicted a reduction in peak inflammation consistent with the difference between the non-surviving and surviving cohorts. This reduction of peak inflammation diminished as the application of LDRT was delayed. The model tracks the available data on viral load, cytokine levels, and inflammatory biomarkers well. An LDRT effect is large enough in principle to provide a life-saving immunomodulatory effect, though patients treated with LDRT already near the peak of their inflammation trajectory are unlikely to see drastic reductions in that peak. This result potentially explains some discrepancies in the preliminary clinical trial data.

The goal of this work is to identify specific treatment planning and delivery features that are prognostic of biochemical failure-free survival (BFFS) for prostate cancer patients treated with external beam radiotherapy (EBRT).This study reviewed patients diagnosed with localized prostate adenocarcinoma between 2005 and 2016, and treated with EBRT on a Varian linear accelerator at one of the four cancer centers in Alberta, Canada. BFFS was calculated using the Kaplan-Meier estimator. Patient demographics, tumor characteristics, and EBRT treatment planning and delivery factors, were collected for each patient. The patient cohort was split into a training dataset with patients from two centers and a validation dataset with patients from another two centers. A random survival forest was used to identify features associated with BFFS.This study included 2827 patients with a median follow-up of 6.4 years. The BFFS for this cohort collectively was 84.9% at 5 years and 69.3% at 10 years. 2519 patients from two centers were used for model training and 308 patients from two different centers were used for model validation. The prognostic features were Gleason score, prostate-specific antigen (PSA) at diagnosis, clinical T stage, CTV D99, pelvic irradiation, IGRT frequency, and PTV V98. Variables including bladder volume, dose calculation algorithm, PTV D99, age at diagnosis, hip prosthesis, number of malignancies, fiducial marker usage, PTV volume, RT modality, PTV HI, rectal volume, hormone treatment, PTV D1cc, equivalent PTV margin, IGRT type, and EQD2_1.5 were unlikely to be prognostic. A random survival forest using only the seven prognostic variables was built. The Harrell's concordance index for the model was 0.65 for the whole training dataset, 0.62 for out-of-bag samples of the training dataset, and 0.62 for the validation dataset.EBRT features prognostic of BFFS were identified and a random survival forest was developed for predicting prostate cancer patients' BFFS after EBRT.

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.

Target dose uniformity has been historically an aim of volumetric modulated arc therapy (VMAT) planning. However, for some sites, this may not be strictly necessary and removing this constraint could theoretically improve organ‐at‐risk (OAR) sparing and tumor control probability (TCP). This study systematically investigates the consequences of PTV dose uniformity that results from the application or removal of an upper dose constraint (UDC) in the inverse planning process for prostate VMAT treatments. OAR sparing, target coverage, hotspots, and plan complexity were compared between prostate VMAT plans with and without the PTV UDC optimized using the progressive resolution optimizer (PRO, Varian Medical Systems, Palo Alto, CA). Removing the PTV UDC, the median D1cc reached 144.6% for the CTV and the PTV, and an average increase of 3.2% TCP was demonstrated, while CTV and PTV coverage evaluated by D99% was decreased by less than 0.6% with statistical significance. Moreover, systematic improvement in the rectum dose volume histograms was shown (a 5–10% decrease in the volume receiving 50% to 75% prescribed dose), resulting in an average decrease of 1.3% (P

One of the main appeals of using gold nanoparticles (GNPs) as radiosensitizers is that their surface coatings can be altered to manipulate their pharmacokinetic properties. However, Monte Carlo studies of GNP dosimetry tend to neglect these coatings, potentially changing the dosimetric results. This study quantifies the dosimetric effects of including a polyethylene glycol (PEG) surface coating on GNPs over both nanoscopic and microscopic ranges. Two dosimetric scales were explored using PENELOPE Monte Carlo simulations. In microscopic simulations, 500-1000 GNPs, with and without coatings, were placed in cavities of side lengths 0.8-4 µm, and the reduction of dose deposited to surrounding medium within these volumes due to the coating was quantified. Including PEG surface coatings of up to 20 nm thickness resulted in reductions of up to 7.5%, 4.0%, and 2.0% for GNP diameters of 10, 20, and 50 nm, respectively. Nanoscopic simulations observed the dose falloff in the first 500 nm surrounding a single GNP both with and without surface coatings of various thicknesses. Over the first 500 nm surrounding a single GNP, the presence of a PEG surface coating reduced dose by 5-26%, 8-28%, 8-30%, and 8-34% for 2, 10, 20, and 50 nm diameter GNPs, respectively, for various energies and coating thicknesses. Reductions in dose enhancement due to the inclusion of a GNP surface coating are non-negligible and should be taken into consideration when investigating GNP dose enhancement. Further studies should be carried out to investigate the biological effects of these coatings.

As a recent area of development in radiation therapy, gold nanoparticle (GNP) enhanced radiation therapy has shown potential to increase tumour dose while maintaining acceptable levels of healthy tissue toxicity. In this study, the effect of varying photon beam energy in GNP enhanced arc radiation therapy (GEART) is quantified through the introduction of a dose scoring metric, and GEART is compared to a conventional radiotherapy treatment. The PENELOPE Monte Carlo code was used to model several simple phantoms consisting of a spherical tumour containing GNPs (concentration: 15 mg Au g(-1) tumour, 0.8 mg Au g(-1) normal tissue) in a cylinder of tissue. Several monoenergetic photon beams, with energies ranging from 20 keV to 6 MeV, as well as 100, 200, and 300 kVp spectral beams, were used to irradiate the tumour in a 360° arc treatment. A dose metric was then used to compare tumour and tissue doses from GEART treatments to a similar treatment from a 6 MV spectrum. This was also performed on a simulated brain tumour using patient computed tomography data. GEART treatments showed potential over the 6 MV treatment for many of the simulated geometries, delivering up to 88% higher mean dose to the tumour for a constant tissue dose, with the effect greatest near a source energy of 50 keV. This effect is also seen with the inclusion of bone in a brain treatment, with a 14% increase in mean tumour dose over 6 MV, while still maintaining acceptable levels of dose to the bone and brain.

Gold nanoparticles (GNPs) have shown potential in recent years as a means of therapeutic dose enhancement in radiation therapy. However, a major challenge in moving towards clinical implementation is the exact characterisation of the dose enhancement they provide. Monte Carlo studies attempt to explore this property, but they often face computational limitations when examining macroscopic scenarios. In this study, a method of converting dose from macroscopic simulations, where the medium is defined as a mixture containing both gold and tissue components, to a mean dose-to-tissue on a microscopic scale was established. Monte Carlo simulations were run for both explicitly-modeled GNPs in tissue and a homogeneous mixture of tissue and gold. A dose ratio was obtained for the conversion of dose scored in a mixture medium to dose-to-tissue in each case. Dose ratios varied from 0.69 to 1.04 for photon sources and 0.97 to 1.03 for electron sources. The dose ratio is highly dependent on the source energy as well as GNP diameter and concentration, though this effect is less pronounced for electron sources. By appropriately weighting the monoenergetic dose ratios obtained, the dose ratio for any arbitrary spectrum can be determined. This allows complex scenarios to be modeled accurately without explicitly simulating each individual GNP.

The purpose of this work was to compare static gantry intensity-modulated radiation therapy (IMRT) with volume-modulated arc therapy (VMAT) in terms of tumor control probability (TCP) under scenarios involving large geometric misses, i.e., those beyond what are accounted for when margin expansion is determined. Using a planning approach typical for these treatments, a linear-quadratic-based model for TCP was used to compare mean TCP values for a population of patients who experiences a geometric miss (i.e., systematic and random shifts of the clinical target volume within the planning target dose distribution). A Monte Carlo approach was used to account for the different biological sensitivities of a population of patients. Interestingly, for errors consisting of coplanar systematic target volume offsets and three-dimensional random offsets, static gantry IMRT appears to offer an advantage over VMAT in that larger shift errors are tolerated for the same mean TCP. For example, under the conditions simulated, erroneous systematic shifts of 15mm directly between or directly into static gantry IMRT fields result in mean TCP values between 96% and 98%, whereas the same errors on VMAT plans result in mean TCP values between 45% and 74%. Random geometric shifts of the target volume were characterized using normal distributions in each Cartesian dimension. When the standard deviations were doubled from those values assumed in the derivation of the treatment margins, our model showed a 7% drop in mean TCP for the static gantry IMRT plans but a 20% drop in TCP for the VMAT plans. Although adding a margin for error to a clinical target volume is perhaps the best approach to account for expected geometric misses, this work suggests that static gantry IMRT may offer a treatment that is more tolerant to geometric miss errors than VMAT.

// Anna Kovalchuk 1 , Richelle Mychasiuk 1 , Arif Muhammad 1 , Shakhawat Hossain 1 , Slava Ilnytskyy 2 , Abhijit Ghose 3 , Charles Kirkby 3, 4 , Esmaeel Ghasroddashti 3, 4 , Olga Kovalchuk 2, 5 , Bryan Kolb 1, 5, 6 1 Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada 2 Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada 3 Jack Ady Cancer Center, Alberta Health Services, Lethbridge, AB, Canada 4 Department of Physics and Astronomy and Department of Oncology, University of Calgary, Calgary, AB, Canada 5 Alberta Epigenetics Network, Calgary, AB, Canada 6 Canadian Institute for Advanced Research, Toronto, ON, Canada Correspondence to: Bryan Kolb, e-mail: kolb@uleth.ca Olga Kovalchuk, e-mail: olga.kovalchuk@uleth.ca Keywords: radiation therapy, brain, neuroanatomy, behaviour, gene expression Received: November 23, 2015 Accepted: November 24, 2015 Published: December 15, 2015 ABSTRACT Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects. We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model. Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

Purpose As automation in radiation oncology becomes more common, it is important to determine which algorithms are equivalent for a given workflow. Often, algorithm comparisons are performed in isolation; however, clinical context can provide valuable insight into the importance of algorithm features and error magnification in subsequent workflow steps. We propose a strategy for deriving workflow-specific algorithm performance requirements. Methods We considered two independent workflows indicating the need for radiotherapy treatment replanning for 15 head and neck cancer patients (15 planning CTs, 105 on-unit CBCTs). Each workflow was based on a different deformable image registration (DIR) algorithm. Differences in DIR output were assessed using three sets of QA metrics: (1) conventional, (2) workflow-specific, (3) a combination of (1) and (2). For a given set of algorithm metrics, lasso logistic regression modeled the probability of discrepant replan indications. Varying the minimum probability needed to predict a workflow discrepancy produced receiver operating characteristic (ROC) curves. ROC curves were compared using sensitivity, specificity, and the area under the curve (AUC). A heuristic then derived simple algorithm performance requirements. Results Including workflow-specific QA metrics improved AUC from 0.70 to 0.85, compared to the use of conventional metrics alone. Algorithm performance requirements had high sensitivity of 0.80, beneficial for replan assessments, with specificity of 0.57. This was an improvement over a naive application of conventional QA criteria, which had sensitivity of 0.57 and specificity of 0.68. In addition, the algorithm performance requirements indicated practical refinements of conventional QA tolerances, indicated where auxiliary workflow processes should be standardized, and may be used to prioritize structures for manual review. Conclusions Our algorithm performance requirements outperformed current comparison recommendations and provided practical means for ensuring workflow equivalence. This strategy may aid in trial credentialing, algorithm development, and streamlining expert adjustment of workflow output.

Algorithm benchmarking and characterization are an important part of algorithm development and validation prior to clinical implementation. However, benchmarking may be limited to a small collection of test cases due to the resource-intensive nature of establishing 'ground-truth' references. This study proposes a framework for selecting test cases to assess algorithm and workflow equivalence. Effective test case selection may minimize the number of ground-truth comparisons required to establish robust and clinically relevant benchmarking and characterization results. To demonstrate the proposed framework, we clustered differences between two independent workflows estimating during-treatment dose objective violations for 15 head and neck cancer patients (15 planning CTs, 105 on-unit CBCTs). Each workflow used a different deformable image registration algorithm to estimate inter-fractional anatomy and contour changes. The Hopkins statistic tested whether workflow output was inherently clustered and k-medoid clustering formalized cluster assignment. Further statistical analyses verified the relevance of clusters to algorithm output. Data at cluster centers ('medoids') were considered as candidate test cases representative of workflow-relevant algorithm differences. The framework indicated that differences in estimated dose objective violations were naturally grouped (Hopkins = 0.75, providing 90% confidence). K-medoid clustering identified five clusters which stratified workflow differences (MANOVA: p

Body contour changes are commonly seen in prostate and head and neck (H&N) patients undergoing volumetric modulated arc therapy (VMAT) treatments, which may cause a discrepancy between the planned dose and the delivered dose. Dosimetrists, radiation oncologists or medical physicists sometimes are required to visually assess the dosimetric impact of body contour changes and make a judgment call on whether further re‐assessment of the plan is needed. However, an intuitive judgment cannot always be made in a timely manner due to the complexity of VMAT plans as well as the complicated forms of body contour changes. This study evaluated the dosimetric effect of body contour changes for prostate and H&N patients to help with clinical decision‐making. By analyzing the one‐dimensional spatial dose profiles from the original body and the body with different body contour deformations, rules of thumb for dose percentage change and isodose line shift due to body contour changes were ascertained. Moreover, based on dose distribution comparison using three‐dimensional gamma analysis, the response of the clinical prostate and H&N VMAT plans to body contour changes was assessed. Within center specific dose deviation tolerances, prostate patients who had less than 2 cm single side body contour change or less than 1 cm uniform body contour change were unlikely to need plan re‐assessment; H&N VMAT plans with less than 1 cm uniform body contour change or less than 1 cm shoulder superior–inferior positional change were also unlikely to trigger further evaluation. Dose percentage change and isodose line shift were considered independently from the problem of volume changes in this study, but clinically, both aspects must be considered.

Purpose To establish a method for estimating skin dose for patients with permanent breast seed implant based on in vivo optically stimulated luminescence dosimeters (OSLDs) measurements. Methods and Materials Monte Carlo simulations were performed in a simple breast phantom using the EGSnrc user code egs_brachy. Realistic models of the IsoAid Advantage Pd-103 brachytherapy source and Landauer nanoDot OSLD were created to model in vivo skin dose measurements where an OSLD would be placed on the skin of a patient with permanent breast seed implant following implantation. Doses to a 0.2 cm3 volume of skin beneath the OSLD and to the sensitive volume within the OSLD were calculated, and the ratio of these values was found for various seed positions inside the breast phantom. The maximum value of this ratio may be used as a conversion factor that would allow skin dose to be estimated from in vivo OSLD measurements. Results Conversion factors of 0.5 and 1.44 are recommended for OSLDs calibrated to dose to Al2O3 and water, respectively, at the point of measurement in the OSLD. These factors were not significantly affected by the addition of extra seeds in the dose calculations. Conclusions A method for estimating skin dose from OSLD measurements was proposed. Individual institutions should calibrate OSLDs to Pd-103 seeds to apply the results of this work clinically.

Purpose: using simulations and models derived from existing literature, this work investigates relative biological effectiveness (RBE) for out-of-field radiation and attempts to quantify the relative magnitudes of different contributing phenomena (spectral, bystander, and low dose hypersensitivity effects). Specific attention is paid to external beam radiotherapy treatments for prostate cancer. Materials and methods: using different biological models that account for spectral, bystander, and low dose hypersensitivity effects, the RBE was calculated for different points moving radially out from isocentre for a typical single arc VMAT prostate case. The RBE was found by taking the ratio of the equivalent dose with the physical dose. Equivalent doses were calculated by determining what physical dose would be necessary to produce the same overall biological effect as that predicted using the different biological models. Results: spectral effects changed the RBE out-of-field less than 2%, whereas response models incorporating low dose hypersensitivity and bystander effects resulted in a much more profound change of the RBE for out-of-field doses. The bystander effect had the largest RBE for points located just outside the edge of the primary radiation beam in the cranial caudal (z-direction) compared to low dose hypersensitivity and spectral effects. In the coplanar direction, bystander effect played the largest role in enhancing the RBE for points up to 8.75 cm from isocentre. Conclusions: spectral, bystander, and low dose hypersensitivity effects can all increase the RBE for out-of-field radiation doses. In most cases, bystander effects seem to play the largest role followed by low dose hypersensitivity. Spectral effects were unlikely to be of any clinical significance. Bystander, low dose hypersensitivity, and spectral effect increased the RBE much more in the cranial caudal direction (z-direction) compared with the coplanar directions.

To account for particle interactions in the extracellular (physical) environment, information from the cell-level Monte Carlo damage simulation (MCDS) for DNA double strand break (DSB) induction has been integrated into the general purpose Monte Carlo N-particle (MCNP) radiation transport code system. The effort to integrate these models is motivated by the need for a computationally efficient model to accurately predict particle relative biological effectiveness (RBE) in cell cultures and in vivo. To illustrate the approach and highlight the impact of the larger scale physical environment (e.g. establishing charged particle equilibrium), we examined the RBE for DSB induction (RBEDSB) of x-rays, (137)Cs γ-rays, neutrons and light ions relative to γ-rays from (60)Co in monolayer cell cultures at various depths in water. Under normoxic conditions, we found that (137)Cs γ-rays are about 1.7% more effective at creating DSB than γ-rays from (60)Co (RBEDSB = 1.017) whereas 60-250 kV x-rays are 1.1 to 1.25 times more efficient at creating DSB than (60)Co. Under anoxic conditions, kV x-rays may have an RBEDSB up to 1.51 times as large as (60)Co γ-rays. Fission neutrons passing through monolayer cell cultures have an RBEDSB that ranges from 2.6 to 3.0 in normoxic cells, but may be as large as 9.93 for anoxic cells. For proton pencil beams, Monte Carlo simulations suggest an RBEDSB of about 1.2 at the tip of the Bragg peak and up to 1.6 a few mm beyond the Bragg peak. Bragg peak RBEDSB increases with decreasing oxygen concentration, which may create opportunities to apply proton dose painting to help address tumor hypoxia. Modeling of the particle RBE for DSB induction across multiple physical and biological scales has the potential to aid in the interpretation of laboratory experiments and provide useful information to advance the safety and effectiveness of hadron therapy in the treatment of cancer.

Purpose: Radiation damage to mitochondria has been shown to alter cellular processes and even lead to apoptosis. Gold nanoparticles (AuNPs) may be used to enhance these effects in scenarios where they collect on the outer membranes of mitochondria. A Monte Carlo (MC) approach is used to estimate mitochondrial dose enhancement under a variety of conditions. Methods: The penelope MC code was used to generate dose distributions resulting from photons striking a 13 nm diameter AuNP with various thicknesses of water-equivalent coatings. Similar dose distributions were generated with the AuNP replaced by water so as to estimate the gain in dose on a microscopic scale due to the presence of AuNPs within an irradiated volume. Models of mitochondria with AuNPs affixed to their outer membrane were then generated—considering variation in mitochondrial size and shape, number of affixed AuNPs, and AuNP coating thickness—and exposed (in a dose calculation sense) to source spectra ranging from 6 MV to 90 kVp. Subsequently dose enhancement ratios (DERs), or the dose with the AuNPs present to that for no AuNPs, for the entire mitochondrion and its components were tallied under these scenarios. Results: For a representative case of a 1000 nm diameter mitochondrion affixed with 565 AuNPs, each with a 13 nm thick coating, the mean DER over the whole organelle ranged from roughly 1.1 to 1.6 for the kilovoltage sources, but was generally less than 1.01 for the megavoltage sources. The outer membrane DERs remained less than 1.01 for the megavoltage sources, but rose to 2.3 for 90 kVp. The voxel maximum DER values were as high as 8.2 for the 90 kVp source and increased further when the particles clustered together. The DER exhibited dependence on the mitochondrion dimensions, number of AuNPs, and the AuNP coating thickness. Conclusions: Substantial dose enhancement directly to the mitochondria can be achieved under the conditions modeled. If the mitochondrion dose can be directly enhanced, as these simulations show, this work suggests the potential for both a tool to study the role of mitochondria in cellular response to radiation and a novel avenue for radiation therapy in that the mitochondria may be targeted, rather than the nuclear DNA.

The Canadian Organization of Medical Physicists (COMP), in close partnership with the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series of Technical Quality Control (TQC) guidelines for radiation treatment equipment. These guidelines outline the performance objectives that equipment should meet in order to ensure an acceptable level of radiation treatment quality. The TQC guidelines have been rigorously reviewed and field tested in a variety of Canadian radiation treatment facilities. The development process enables rapid review and update to keep the guidelines current with changes in technology (the most updated version of this guideline can be found on the CPQR website). This particular TQC details recommended quality control testing for medical linear accelerators and multileaf collimators.

In light of in vitro evidence suggesting that radiation-induced bystander effects may enhance non-local cell killing, there is potential for impact on radiotherapy treatment planning paradigms such as the goal of delivering a uniform dose throughout the clinical target volume (CTV). This work applies a bystander effect model to calculate equivalent uniform dose (EUD) and tumor control probability (TCP) for external beam prostate treatment and compares the results with a more common model where local response is dictated exclusively by local absorbed dose. The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context.EUD and TCP of a prostate cancer target volume under conditions of increasing dose heterogeneity were calculated using two models: One incorporating bystander effects derived from previously published in vitro bystander data ( McMahon et al. 2012 , 2013a); and one using a common linear-quadratic (LQ) response that relies exclusively on local absorbed dose. Dose through the CTV was modelled as a normal distribution, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). Also, a representative clinical dose distribution was examined as cold (low dose) sub-volumes were systematically introduced.The bystander model suggests a moderate degree of dose heterogeneity throughout a target volume will yield as good or better outcome compared to a uniform dose in terms of EUD and TCP. For a typical intermediate risk prostate prescription of 78 Gy over 39 fractions maxima in EUD and TCP as a function of increasing SD occurred at SD ∼ 5 Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. Small, but potentially significant differences in the outcome metrics between the models were identified in the clinically-derived dose distribution as cold sub-volumes were introduced.In terms of EUD and TCP, the bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV varies. The results suggest, at least in a limiting sense, the potential for allowing some degree of dose heterogeneity within a CTV, although further investigation of the assumptions of the bystander model are warranted.

PURPOSE The radiation dose enhancement caused by introducing gold nanoparticles (GNP) into cells can increase the dose locally absorbed. A disconnect between experimentally determined survival and dose enhancements predicted by Monte Carlo simulations on macroscopic scales, suggests small-scale energy deposition patterns play an important role in GNP dose enhancement. Clustering of the GNPs could potentially alter small-scale energy deposition patterns. Here we use Monte Carlo simulations to quantify energy deposition patterns in the presence of clustered GNPs and address the question of whether clustering of the nanoparticles affects the energy deposition patterns and ultimately cellular response. METHODS Using the PENELOPE Monte Carlo code, we examine the absorption of energy in the environment of a single irradiated GNP following its interaction with a set of primary monoenergetic photon beams. We introduce successive GNPs to form a cluster about the particle in which the primary photon interactions occur and report on the energy deposited locally (within a 500 nm radius) and nonlocally (beyond 500 nm) in the surrounding water-equivalent medium as a function of the number of additional GNPs and the packing geometry they assume. RESULTS When additional GNPs cluster in tightly packed formations about a GNP in which an incident photon interacts, both the energy deposited locally and released nonlocally are reduced relative to the case where other GNPs are not present. The degree of the reduction depends on incident photon energy, the number of GNPs added to the cluster, and the packing geometry. With 90 additional GNPs in a hexagonal close packing (HCP) cluster about a directly irradiated test particle, the local energy deposition was reduced to 29% (of the value in the absence of neighbors) in the most extreme monoenergetic case. Energy released into the nonlocal volume was most affected by the cluster for low-incident photon energies (< 40 keV), where reductions to 26% of the value in the absence of a cluster were shown. The packing geometry mitigated these results. When the irradiated GNP was on the periphery of the HCP cluster, or when the cluster was confined to a plane, the observed effects were weaker and when an equal number of GNPs were uniformly distributed in the local volume, the changes were trivial (less than 2%). CONCLUSIONS The findings provide grounds for reconciling the observations of cell survival with Monte Carlo predictions of GNP dose enhancement. This work is significant because it demonstrates that GNP clustering needs to be understood and accounted to optimize local dose enhancement.

OBJECTIVE: Modern image-guided small animal irradiators like the Xstrahl Small Animal Radiation Research Platform (SARRP) are designed with ultrathin 0.15 mm Cu filters, which compared with more heavily filtrated traditional cabinet-style biological irradiators, produce X-ray spectra weighted toward lower energies, impacting the dosimetric properties and the relative biological effectiveness (RBE). This study quantifies the effect of ultrathin filter design on relative depth dose profiles, absolute dose output, and RBE using Monte Carlo techniques. METHODS: The percent depth-dose and absolute dose output are calculated using kVDoseCalc and EGSnrc, respectively, while a tally based on the induction of double-strand breaks as a function of electron spectra invoked in PENELOPE is used to estimate the RBE. RESULTS: The RBE increases by >2.4% in the ultrathin filter design compared to a traditional irradiator. Furthermore, minute variations in filter thickness have notable effects on the dosimetric properties of the X-ray beam, increasing the percent depth dose (at 2 cm in water) by + 0.4%/0.01 mm Cu and decreasing absolute dose (at 2 cm depth in water) by –1.8%/0.01 mm Cu for the SARRP. CONCLUSIONS: These results show that modern image-guided irradiators are quite sensitive to small manufacturing variations in filter thickness, and show a small change in RBE compared to traditional X-ray irradiators. ADVANCES IN KNOWLEDGE: We quantify the consequences of ultrathin filter design in modern image-guided biological irradiators on relative and absolute dose, and RBE. Our results show these to be small, but not insignificant, suggesting laboratories transitioning between irradiators should carefully design their radiobiological experiments.

Due to the higher LET of kilovoltage (kV) radiation, there is potential for an increase in relative biological effectiveness (RBE) of absorbed doses of radiation from kV cone beam computed tomography (CBCT) sources in reference to megavoltage or Co-60 doses. This work develops a method for accurately coupling a Monte Carlo (MC) radiation transport code (PENELOPE) with the damage simulation (MCDS) to predict relative numbers of DNA double strand breaks (DSBs). The MCDS accounts for slowing down of electrons and delta ray production within the cell nucleus; however, determining the spectrum of electrons incident on the cell nucleus from photons interacting in a larger region of tissue is not trivial. PENELOPE simulations were conducted with a novel tally algorithm invoked where electrons incident on a detection material were tracked and both the incident energy and the final deposited dose were recorded. The DSB yield predicted by a set of MCDS runs of monoenergetic electrons was then looked up in a table and weighted by the specific energy of the incident electron. Our results indicate that the RBE for DSB induction is 1.1 for diagnostic x-rays with energies from 80 to 125 kVp. We found no significant change in RBE with depth or filtration. The predicted absolute DSB yields are about three times lower for cells irradiated under anoxic conditions than the yield in cells irradiated under normoxic (5%) or fully aerobic (100%) conditions. However, oxygen concentration has a negligible (± 0.02) effect on the RBE of kV CBCT x-rays.

In radiation biology, rats are often irradiated, but the precise dose distributions are often lacking, particularly in areas that receive scatter radiation. We used a non-dedicated set of resources to calculate detailed dose distributions, including doses to peripheral organs well outside of the primary field, in common rat exposure settings.We conducted a detailed dose reconstruction in a rat through an analog to the conventional human treatment planning process. The process consisted of: (i) Characterizing source properties of an X-ray irradiator system, (ii) acquiring a computed tomography (CT) scan of a rat model, and (iii) using a Monte Carlo (MC) dose calculation engine to generate the dose distribution within the rat model. We considered cranial and liver irradiation scenarios where the rest of the body was protected by a lead shield. Organs of interest were the brain, liver and gonads. The study also included paired scenarios where the dose to adjacent, shielded rats was determined as a potential control for analysis of bystander effects.We established the precise doses and dose distributions delivered to the peripheral organs in single and paired rats. Mean doses to non-targeted organs in irradiated rats ranged from 0.03-0.1% of the reference platform dose. Mean doses to the adjacent rat peripheral organs were consistent to within 10% those of the directly irradiated rat.This work provided details of dose distributions in rat models under common irradiation conditions and established an effective scenario for delivering only scattered radiation consistent with that in a directly irradiated rat.

Purpose The magnetic fields of linac-MR systems modify the path of contaminant electrons in photon beams, which alters patient skin dose. To accurately quantify the magnitude of changes in skin dose, the authors use Monte Carlo calculations that incorporate realistic 3D magnetic field models of longitudinal and transverse linac-MR systems. Methods Finite element method (FEM) is used to generate complete 3D magnetic field maps for 0.56 T longitudinal and transverse linac-MR magnet assemblies, as well as for representative 0.5 and 1.0 T Helmholtz MRI systems. EGSnrc simulations implementing these 3D magnetic fields are performed. The geometry for the BEAMnrc simulations incorporates the Varian 600C 6 MV linac, magnet poles, the yoke, and the magnetic shields of the linac-MRIs. Resulting phase-space files are used to calculate the central axis percent depth-doses in a water phantom and 2D skin dose distributions for 70 μm entrance and exit layers using DOSXYZnrc. For comparison, skin doses are also calculated in the absence of magnetic field, and using a 1D magnetic field with an unrealistically large fringe field. The effects of photon field size, air gap (longitudinal configuration), and angle of obliquity (transverse configuration) are also investigated. Results Realistic modeling of the 3D magnetic fields shows that fringe fields decay rapidly and have a very small magnitude at the linac head. As a result, longitudinal linac-MR systems mostly confine contaminant electrons that are generated in the air gap and have an insignificant effect on electrons produced further upstream. The increase in the skin dose for the longitudinal configuration compared to the zero B-field case varies from ∼1% to ∼14% for air gaps of 5-31 cm, respectively. (All dose changes are reported as a % of D(max).) The increase is also field-size dependent, ranging from ∼3% at 20 × 20 cm(2) to ∼11% at 5 × 5 cm(2). The small changes in skin dose are in contrast to significant increases that are calculated for the unrealistic 1D magnetic field. For the transverse configuration, the entrance skin dose is equal or smaller than that of the zero B-field case for perpendicular beams. For a 10 × 10 cm(2) oblique beam the transverse magnetic field decreases the entry skin dose for oblique angles less than ±20° and increases it by no more than 10% for larger angles up to ±45°. The exit skin dose is increased by 42% for a 10 × 10 cm(2) perpendicular beam, but appreciably drops and approaches the zero B-field case for large oblique angles of incidence. Conclusions For longitudinal linac-MR systems only a small increase in the entrance skin dose is predicted, due to the rapid decay of the realistic magnetic fringe fields. For transverse linac-MR systems, changes to the entrance skin dose are small for most scenarios. For the same geometry, on the exit side a fairly large increase is observed for perpendicular beams, but significantly drops for large oblique angles of incidence. The observed effects on skin dose are not expected to limit the application of linac-MR systems in either the longitudinal or transverse configuration.

Changing pulse repetition frequency or dose rate used for IMRT treatments can alter the number of monitor units (MUs) and the time required to deliver a plan. This work was done to develop a practical picture of the magnitude of these changes. We used Varian's Eclipse Treatment Planning System to calculate the number of MUs and beam‐on times for a total of 40 different treatment plans across an array of common IMRT sites including prostate/pelvis, prostate bed, head and neck, and central nervous system cancers using dose rates of 300, 400 and 600 MU/min. In general, we observed a 4%–7% increase in the number of MUs delivered and a 10–40 second decrease in the beam‐on time for each 100 MU/min of dose rate increase. The increase in the number of MUs resulted in a reduction of the “beam‐on time saved”. The exact magnitude of the changes depended on treatment site and planning target volume. These changes can lead to minor, but not negligible, concerns with respect to radiation protection and treatment planning. Although the number of MUs increased more rapidly for more complex treatment plans, the absolute beam‐on time savings was greater for these plans because of the higher total number of MUs required to deliver them. We estimate that increasing the IMRT dose rate from 300 to 600 MU/min has the potential to add up to two treatment slots per day for each IMRT linear accelerator. These results will be of value to anyone considering general changes to IMRT dose rates within their clinic. PACS number: 87.55.N

Purpose : There is interest in developing linac-MR systems for MRI-guided radiation therapy. To date, the designs for such linac-MR devices have been restricted to a transverse geometry where the static magnetic field is oriented perpendicular to the direction of the incident photon beam. This work extends possibilities in this field by proposing and examining by Monte Carlo simulations, a probable longitudinal configuration where the magnetic field is oriented in the same direction as the photon beam. Methods : The EGSnrc Monte Carlo (MC) radiation transport codes with algorithms implemented to account for the magnetic field deflection of charged particles were used to compare dose distributions for linac-MR systems in transverse and longitudinal geometries. Specifically, the responses to a 6 MV pencil photon beam incident on water and lung slabs were investigated for 1.5 and 3.0 T magnetic fields. Further a five field lung plan was simulated in the longitudinal and transverse geometries across a range of magnetic field strengths from 0.2 through 3.0 T. Results : In a longitudinal geometry, the magnetic field is shown to restrict the radial spread of secondary electrons to a small degree in water, but significantly in low density tissues such as lung in contrast to the lateral shift in dose distribution seen in the transverse geometry. These effects extend to the patient case, where the longitudinal configuration demonstrated dose distributions more tightly confined to the primary photon fields, which increased dose to the planning target volume (PTV), bettered dose homogeneity within a heterogeneous (in density) PTV, and reduced the tissue interface effects associated with the transverse geometry. Conclusions : Dosimetry issues observed in a transverse linac-MR geometry such as changes to the depth dose distribution and tissue interface effects were significantly reduced or eliminated in a longitudinal geometry on a representative lung plan. Further, an increase in dose to the PTV, resulting from the magnetic field confining electrons to the forward direction, shows potential for a reduction in dose to the surrounding tissues.

Purpose: The details of a full simulation of an inline side-coupled 6 MV linear accelerator(linac) from the electron gun to the target are presented. Commissioning of the above simulation was performed by using the derived electron phase space at the target as an input into Monte Carlo studies of dose distributions within a water tank and matching the simulation results to measurement data. This work is motivated by linac-MR studies, where a validated full linac simulation is first required in order to perform future studies on linac performance in the presence of an external magnetic field. Methods: An electron gun was initially designed and optimized with a 2D finite difference program using Child’s law. The electron gun simulation served as an input to a 6 MV linac waveguide simulation, which consisted of a 3D finite element radio-frequency field solution within the waveguide and electron trajectories determined from particle dynamics modeling. The electron gun design was constrained to match the cathode potential and electron gun current of a Varian 600C, while the linac waveguide was optimized to match the measured target current. Commissioning of the full simulation was performed by matching the simulated Monte Carlodose distributions in a water tank to measured distributions. Results: The full linac simulation matched all the electrical measurements taken from a Varian 600C and the commissioning process lead to excellent agreements in the dose profile measurements. Greater than 99% of all points met a 1%/1mm acceptance criterion for all field sizes analyzed, with the exception of the largest 40 × 40 cm 2 field for which 98% of all points met the 1%/1mm acceptance criterion and the depth dose curves matched measurement to within 1% deeper than 1.5 cm depth. The optimized energy and spatial intensity distributions, as given by the commissioning process, were determined to be non-Gaussian in form for the inline side-coupled 6 MV linac simulated. Conclusions: An integrated simulation of an inline side-coupled 6 MV linac has been completed and benchmarked matching all electrical and dosimetricmeasurements to high accuracy. The results showed non-Gaussian spatial intensity and energy distributions for the linac modeled.

Scattered radiation in the penumbra of a megavoltage radiation therapy beam can deposit a non-negligible dose in the healthy tissue around a target volume. The lower energy of the radiation in this region suggests that its biological effectiveness might not be the same as that of the open beam. In this work, we determined the relative biological damage in normal human fibroblasts after megavoltage irradiation in two geometries. The first was an open-beam irradiation and the second was a blocked configuration in which only scattered radiation could reach the target cells. The biological damage was evaluated by the gamma-H2AX immunofluorescence assay, which is capable of detecting DNA double-strand breaks in individual cells. We report that the scattered radiation is more effective at producing biological damage than the open beam radiation. We found a 27% enhancement in the net mean nuclear gamma-H2AX fluorescence intensity at 2 Gy and a 48% enhancement at 4 Gy. These findings are of interest due to the increased doses of penumbral radiation close to target volumes both in dose escalation studies and in IMRT treatment deliveries where high dose gradients exist for the purpose of conformal avoidance of healthy tissues.

Several groups worldwide have proposed various concepts for improving megavoltage (MV) radiotherapy that involve irradiating patients in the presence of a magnetic field-either for image guidance in the case of hybrid radiotherapy-MRI machines or for purposes of introducing tighter control over dose distributions. The presence of a magnetic field alters the trajectory of charged particles between interactions with the medium and thus has the potential to alter energy deposition patterns within a sub-cellular target volume. In this work, we use the MC radiation transport code PENELOPE with appropriate algorithms invoked to incorporate magnetic field deflections to investigate electron energy fluence in the presence of a uniform magnetic field and the energy deposition spectra within a 10 microm water sphere as a function of magnetic field strength. The simulations suggest only very minor changes to the electron fluence even for extremely strong magnetic fields. Further, calculations of the dose-averaged lineal energy indicate that a magnetic field strength of at least 70 T is required before beam quality will change by more than 2%.

Helical tomotherapy is an increasingly common form of intensity modulated radiation therapy that allows for image guided adaptive radiotherapy. Its treatment planning system (TPS) uses a convolution superposition algorithm for dose distribution calculations. The accuracy of this algorithm in the presence of heterogeneities was evaluated against Monte Carlo (MC) calculations and measurements. This work performed BEAMnrc-and DOSXYZnrc-based MC dose calculations of tomotherapy deliveries to a CIRS anthropomorphic heterogeneous phantom with typical clinical inverse planning and delivery settings. Point measurements with A1SL ion chambers and relative measurements with Kodak EDR2 film were carried out in the phantom. The experimental results were used to evaluate both the TPS and MC dose calculations. Furthermore, the dose distribution for a clinical head-and-neck cancer plan was calculated on the TPS and MC systems. The results support this MC system as a viable option for the accurate simulation of the tomotherapy process in the presence of heterogeneities where direct measurement may not be practical. Ion chamber measurements in the CIRS phantom suggested the TPS has an average relative difference of 2.3%, with the largest difference being -4.1% in one of the organs at risk. The MC system accurately predicted the dose to these measurement points within statistical uncertainty. The film measurements in the CIRS phantom demonstrated 90.7% (of pixels) agreed with the MC system using a +/-3%/3 mm acceptance criteria, where only 50.3% agreed with the TPS. In the clinical head-and-neck cancer plan evaluation where MC served as a reference against which to compare the TPS result, an average of 92.7% of the voxels within volumes of interest passed a 3%/3 mm criteria. The PTV54 showed the worst agreement with 85.4% of the volume passing the 3% /3 mm criteria. In general, the +/-3%/3 mm criterion was found to be a challenge for the TPS in the presence of lung inhomogeneity.

Helical tomotherapy delivers intensity modulated radiation therapy using a binary multileaf collimator (MLC) to modulate a fan beam of radiation. This delivery occurs while the linac gantry and treatment couch are both in constant motion, so the beam describes, from a patient/phantom perspective, a spiral or helix of dose. The planning system models this continuous delivery as a large number (51) of discrete gantry positions per rotation, and given the small jaw/fan width setting typically used (1 or 2.5 cm) and the number of overlapping rotations used to cover the target (pitch often

A novel geometry has been proposed for a hybrid magnetic resonance imaging (MRI)-linac system in which a 6 MV linac is mounted on the open end of a biplanar, low field (0.2 T) MRI magnet on a single gantry that is free to rotate around the patient. This geometry creates a scenario in which the magnetic field vector remains fixed with respect to the incident photon beam, but moves with respect to the patient as the gantry rotates. Other proposed geometries are characterized by a radiation source rotating about a fixed cylindrical magnet where the magnetic field vector remains fixed with respect to the patient. In this investigation we simulate the inherent dose distribution patterns within the two MRI-radiation source geometries using PENELOPE and EGSnrc Monte Carlo radiation transport codes with algorithms implemented to account for the magnetic field deflection of charged particles. Simulations are performed in phantoms and for clinically realistic situations. The novel geometry results in a net Lorentz force that remains fixed with respect to the patient (in the cranial-caudal direction) and results in a cumulative influence on dose distribution for a multiple beam treatment scenario. For a case where patient anatomy is reasonably homogeneous (brain plan), differences in dose compared to a conventional (no magnetic field) case are minimal for the novel geometry. In the case of a lung plan where the inhomogeneous patient anatomy allows for the magnetic field to have significant influence on charged particle transport, larger differences occur in a predictable manner. For a system using a fixed cylindrical geometry and higher magnetic field (1.5 T), differences from the case without a magnetic field are significantly greater.

One of the attractive features of amorphous silicon electronic portal imaging devices (a-Si EPIDs) as dosimetric tools is that for open fields they are known to exhibit a generally linear relation between pixel value and incident energy fluence as measured by an ion chamber. It has also been established that a-Si EPIDs incorporating high atomic number phosphors such as Gd{sub 2}O{sub 2}S:Tb exhibit a disproportionately large response to low-energy (

Images produced by commercial amorphous silicon electronic portal imaging devices ( a -Si EPIDs) are subject to multiple blurring processes. Implementation of these devices for fluence measurement requires that the blur be removed from the images. A standard deconvolution operation can be performed to accomplish this assuming the blur kernel is spatially invariant and accurately known. This study determines a comprehensive blur kernel for the Varian aS500 EPID. Monte Carlo techniques are used to derive a dose kernel and an optical kernel, which are then combined to yield an overall blur kernel for both 6 and 15 MV photon beams. Experimental measurement of the line spread function (LSF) is used to verify kernel shape. Kernel performance is gauged by comparing EPIDimage profiles with in-air dose profiles measured using a diamonddetector (approximating fluence) both before and after the EPIDimages have been deconvolved. Quantitative comparisons are performed using the χ metric, an extension of the well-known γ metric, using acceptance criteria of 0.0784 cm (1 pixel width) distance-to-agreement ( Δ d ) and 2% of the relative central axis fluence ( Δ D ) . Without incorporating any free parameters, acceptance was increased from 49.0% of pixels in a cross-plane profile for a 6 MV 10 × 10 cm 2 open field to 92.0%. For a 10 × 10 cm 2 physically wedged field, acceptance increased from 40.3% to 73.9%. The effect of the optical kernel was found to be negligible for these χ acceptance parameters, however for ( Δ D = 1 % , Δ d = 0.0784 cm ) we observed an improvement from 66.1% (without) to 78.6% (with) of χ scores 1 (from 20.6% before deconvolution). It is demonstrated that an empirical kernel having a triple exponential form or a semiempirical kernel based on a simplified model of the detector stack can match the performance of the comprehensive kernel.

Introduction: Gold nanoparticles (GNPs) can enhance radiation therapy within a tumour, increasing local energy deposition under irradiation, but experimental evidence suggests the enhancement is not as large as predicted by dose enhancement alone. Many studies neglect to account for surface coatings that are frequently used to optimize GNP uptake and biological distribution. This study uses Monte Carlo methods to investigate the consequences on local dose enhancement due to including these surface coatings. Methods: Using the PENELOPE Monte Carlo code system, GNP irradiation was simulated both with and without surface coatings of polyethylene glycol (PEG) of various molecular weights. Dose was scored to the gold, coating, and surrounding water, and the dosimetric differences between these scenarios were examined. Results: The simulated PEG coating absorbs a large portion of the energy that would otherwise be deposited in the medium. The mean dose to water was reduced by up to 2.5, 3.5, and 4.5% for GNPs of diameters 50, 20, and 10 nm, respectively. This effect was more pronounced for smaller GNPs, thicker coatings, and low photon source energies where the enhancement due to GNPs is the greatest. The molecular weight of the coating material did not have a significant impact on the dose. Conclusions: The inclusion of a coating material in GNP enhanced radiation may reduce the dose enhancement due to the nanoparticles. Both the composition and size of the coating play a role in the level of this reduction and should be considered carefully.

Purpose: Gold nanoparticles (GNPs) can enhance radiotherapy effects. The high photoelectric cross section of gold relative to tissue, particularly at lower energies, leads to localized dose enhancement. However in a clinical context, photon energies must also be sufficient to reach a target volume at a given depth. These properties must be balanced to optimize such a therapy. Given that nanoscale energy deposition patterns around GNPs play a role in determining biological outcomes, in this work we seek to establish their role in this optimization process. Methods: The PENELOPE Monte Carlo code was used to generate spherical dose deposition kernels in 1000 nm diameter spheres around 50 nm diameter GNPs in response to monoenergetic photons incident on the GNP. Induced “lesions” were estimated by either a local effect model (LEM) or a mean dose model (MDM). The ratio of these estimates was examined for a range of photon energies (10 keV to 2 MeV), for three sets of linear-quadratic parameters. Results: The models produce distinct differences in expected lesion values, the lower the alpha-beta ratio, the greater the difference. The ratio of expected lesion values remained constant within 5% for energies of 40 keV and above across all parameter sets and rose to a difference of 35% for lower energies only for the lowest alpha-beta ratio. Conclusion: Consistent with other work, these calculations suggest nanoscale energy deposition patterns matter in predicting biological response to GNP-enhanced radiotherapy. However the ratio of expected lesions between the different models is largely independent of energy, indicating that GNP-enhanced radiotherapy scenarios can be optimized in photon energy without consideration of the nanoscale patterns. Special attention may be warranted for energies of 20 keV or below and low alpha-beta ratios.

A new electron distribution function has been found in laser heated homogeneous plasmas by an analytical solution to the kinetic equation and by particle simulations. The basic kinetic model describes inverse bremsstrahlung absorption and electron–electron collisions. The non-Maxwellian distribution function is comprised of a super-Gaussian bulk of slow electrons and a Maxwellian tail of energetic particles. The tails are heated due to electron–electron collisions and energy redistribution between superthermal particles and light absorbing slow electrons from the bulk of the distribution function. A practical fit is proposed to the new electron distribution function. Changes to the linear Landau damping of electron plasma waves are discussed. The first evidence for the existence of non-Maxwellian distribution functions has been found in the interpretation, which includes the new distribution function, of the Thomson scattering spectra in gold plasmas [Glenzer et al., Phys. Rev. Lett. 82, 97 (1999)].

This work investigated the potential implications on tumour control probability (TCP) for external beam prostate cancer treatment when considering the bystander effect in partial exposure scenarios.The biological response of a prostate cancer target volume under conditions where a sub-volume of the target volume was not directly irradiated was modelled in terms of surviving fraction (SF) and Poisson-based TCP. A direct comparison was made between the linear-quadratic (LQ) response model, and a response model that incorporates bystander effects as derived from published in vitro data by McMahon et al. in 2012 and 2013. Scenarios of random and systematic misses were considered.Our results suggested the potential for the bystander effect to deviate from LQ predictions when even very small (1%) sub-volumes of the target volume were directly irradiated. Under conditions of random misses for each fraction, the bystander model predicts a 3% and 1% improvement in tumour control compared to that predicted by an LQ model when only 90% and 95% of the prostate cells randomly receive the intended dose. Under conditions of systematic miss, if even a small portion of the target volume is not directly exposed, the LQ model predicts a TCP approaching zero, whereas the bystander model suggests TCP will improve starting at exposed volumes of around 85%.The bystander model, when applied to clinically relevant scenarios, demonstrates the potential to deviate from the TCP predictions of the common local LQ model when sub-volumes of a target volume are randomly or systematically missed over a course of fractionated radiation therapy.

The objective of this work is to develop a comprehensive radiation treatment planning (RTP) procedure for the therapy of cancer sites based solely on magnetic resonance imaging (MRI), MRI-based RTP. We also investigate the applications of this procedure to a linac-MR system, i.e. a 6 MV therapy accelerator coupled to a bi-planar 0.2 T permanent magnet. The proposed technique consists of a) correction of MR images for scanner-related and patient-induced distortions by using phantom measurements and numerical simulations, respectively, b) segmentation of anatomical structures relevant to dosimetric calculations (i.e. soft-tissue, bone and air), c) conversion of MR images into computed tomography (CT)-like images, by assigning bulk CT values to anatomical contours, along with RTP dose calculations, and d) CT+MRI and MRI-based treatment plan comparison. In addition, for a linac-MR system the RTP dosimetric calculations were performed in the presence of a 0.2 T external magnetic field. Both scanner-related and patient-induced distortion fields were determined. Treatment plans were generated to validate the MRI-based RTP procedure.

Purpose: Monte Carlo studies of gold nanoparticle (GNP) dose enhancement on macroscopic scales in radiotherapy have modeled GNPs in tissue as a homogeneous mixture of gold and tissue. Using an explicit model of GNPs randomly positioned in a small volume (1 µm3) of tissue, this study aims to quantify the dose to the biologically relevant component of a goldtissue mixture, enabling a conversion from macroscopically-scored dose. Methods: Using the PENELOPE Monte Carlo code with the penEasy package, we modeled a 1 µm3 volume containing either a tissue-gold mixture or GNPs suspended in ICRU 4-component tissue at various gold concentrations (0, 5, 10, and 15 mg Au/g tissue) and GNP diameters (20, 30, 40, 50 nm). The volume was irradiated with monoenergetic photon and electron beams, ranging from 110 eV to 6 MeV. Interaction forcing was utilized to increase simulation efficiency. Energy deposition was scored in the tissue for each case and was converted to dose. For each scenario, we calculated a conversion factor, the ratio of dose-to-tissue to dose-to-mixture as a function of energy. Results: The conversion factor was plotted as a function of energy for both photons and electrons. For electrons, the conversion factor was relatively unaffected by any of the parameters, including energy, ranging between 0.98–1.02. For photons, the factor was very energy dependent, with a range of 0.49–1.02. The factor was lowest for 10–100 keV photons. The conversion factor generally decreased with increasing GNP concentration and increasing GNP size. Conclusion: With a large variation in the conversion factor with incident energy, dose deposition is dependent on the spectrum incident on a volume. By scoring the energy spectrum in a given volume, one can provide a scenario-specific conversion factor, allowing fast, detailed Monte Carlo simulations without the need for explicit GNP-definition.

Single event spectra for five beta-emitting radionuclides (Lu-177, Cu-67, Re-186, Re-188, Y-90) were calculated for single cells from two source geometries. The first was a surface-bound isotropically emitting point source and the second was a bath of free radioactivity in which the cell was submerged. Together these represent a targeted intraperitoneal radionuclide therapy. Monoenergetic single event spectra were calculated over an energy range of 11 keV to 2500 keV using the EGSnrc Monte Carlo system. Radionuclide single event spectra were constructed by weighting monoenergetic single event spectra according to radionuclide spectra appropriate for each source geometry. In the case of surface-bound radioactivity, these were radionuclide beta decay spectra. For the free radioactivity, a continuous slowing down approximation spectrum was used that was calculated based on the radionuclide decay spectra. The frequency mean specific energy per event increased as the energy of the beta emitter decreased. This is because, at these energies, the stopping power of the electrons decreases with increasing energy. The free radioactivity produced a higher frequency mean specific energy per event than the corresponding surface-bound value. This was primarily due to the longer mean path length through the target for this geometry. This information differentiates the radionuclides in terms of the physical process of energy deposition and could be of use in the radionuclide selection procedure for this type of therapy.

When performed daily, cone beam CT (CBCT) images can accumulate radiation dose to non-negligible levels. Because kV x-rays have a larger relative biological effectiveness (RBE) than its MV x-rays, the accumulated absorbed dose needs to be multiplied by an appropriate RBE to better evaluate the impact of CBCT dose in a treatment planning context. We investigated this question using PENLEOPE simulations to look in detail at the electron energy spectra produced by kV x-rays and Co-60 γ-rays in biologically motivated geometries. The electron spectra were input into the published Monte Carlo Damage Simulation (MCDS) and used to estimate the average number of double strand breaks (DSBs) per Gy per cell. Our results suggest an approximately 10% increase in the RBE for DSB induction. For the majority of treatment planning scenarios where imaging dose is only a small fraction of the total delivered dose to target volumes and organs at risk, the increase in RBE is not critical to be factored in, however for it may play a significant role in predicting the induction of secondary cancers.

In vitro evidence has suggested that radiation induced bystander effects may enhance non-local cell killing which may influence radiotherapy treatment planning paradigms. This work applies a bystander effect model, which has been derived from published in vitro data, to calculate equivalent uniform dose (EUD) and tumour control probability (TCP) and compare them with predictions from standard linear quadratic (LQ) models that assume a response due only to local absorbed dose. Comparisons between the models were made under increasing dose heterogeneity scenarios. Dose throughout the CTV was modeled with normal distributions, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. The bystander model suggests a moderate degree of dose heterogeneity yields as good or better outcome compared to a uniform dose in terms of EUD and TCP. Intermediate risk prostate prescriptions of 78 Gy over 39 fractions had maximum EUD and TCP values at SD of around 5Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. The bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV is varies. The results suggest the potential for allowing some degree of dose heterogeneity within a CTV, although further investigations of the assumptions of the bystander model are warranted.