Technical note: GAMMORA,a free,open-source,and validated GATE-based model for Monte-Carlo simulations of the Varian TrueBeam

PurposeMonte Carlo (MC) is the reference computation method for medical physics. In radiotherapy, MC computations are necessary for some issues (such as assessing figures of merit, double checks, and dose conversions). A tool based on GATE is proposed to easily create full MC simulations of the Varian TrueBeam STx.MethodsGAMMORA is a package that contains photon phase spaces as a pre-trained generative adversarial network (GAN) and the TrueBeam’s full geometry. It allows users to easily create MC simulations for simple or complex radiotherapy plans such as VMAT. To validate the model, the characteristics of generated photons are first compared to those provided by Varian (IAEA format). Simulated data are also compared to measurements in water and heterogeneous media. Simulations of 8 SBRT plans are compared to measurements (in a phantom). Two examples of applications (a second check and interplay effect assessment) are presented.ResultsThe simulated photons generated by the GAN have the same characteristics (energy, position, and direction) as the IAEA data. Computed dose distributions of simple cases (in water) and complex plans delivered in a phantom are compared to measurements, and the Gamma index (3%/3mm) was always superior to 98%. The feasibility of both clinical applications is shown.ConclusionsThis model is now shared as a free and open-source tool that generates radiotherapy MC simulations. It has been validated and used for five years. Several applications can be envisaged for research and clinical purposes.     

A parametric study of occupational radiation dose in interventional radiology by Monte-Carlo simulations

This paper presents the results of a parametric study on the occupational exposure in interventional radiology to explore the influence of various variables on the staff doses. These variables include the angiography beam settings: x-ray peak voltage (kVp), added copper filtration, field diameter, beam projection and source to detector distance. The study was performed using Monte-Carlo simulations with MCNPX for more than 5600 combinations of parameters that account for different clinical situations. Additionally, the analysis of the results was performed using both multiple and random forest regression to build a predictive model and to quantify the importance of each variable when the variables simultaneously change. Primary and secondary projections were found to have the most effect on the scatter fraction that reaches the operator followed by the effect of changing the x-ray beam quality. The effect of changing the source to image intensifier distance had the lowest effect.     

A software platform for statistical evaluation of patient respiratory patterns in radiation therapy

AimThe aim of this work was to design and evaluate a software tool for analysis of a patient’s respiration, with the goal of optimizing the effectiveness of motion management techniques during radiotherapy imaging and treatment.Materials and methodsA software tool which analyses patient respiratory data files (.vxp files) created by the Varian Real-Time Position Management System (RPM) was developed to analyse patient respiratory data. The software, called RespAnalysis, was created in MATLAB and provides four modules, one each for determining respiration characteristics, providing breathing coaching (biofeedback training), comparing pre and post-training characteristics and performing a fraction-by-fraction assessment. The modules analyse respiratory traces to determine signal characteristics and specifically use a Sample Entropy algorithm as the key means to quantify breathing irregularity. Simulated respiratory signals, as well as 91 patient RPM traces were analysed with RespAnalysis to test the viability of using the Sample Entropy for predicting breathing regularity.ResultsRetrospective assessment of patient data demonstrated that the Sample Entropy metric was a predictor of periodic irregularity in respiration data, however, it was found to be insensitive to amplitude variation. Additional waveform statistics assessing the distribution of signal amplitudes over time coupled with Sample Entropy method were found to be useful in assessing breathing regularity.ConclusionsThe RespAnalysis software tool presented in this work uses the Sample Entropy method to analyse patient respiratory data recorded for motion management purposes in radiation therapy. This is applicable during treatment simulation and during subsequent treatment fractions, providing a way to quantify breathing irregularity, as well as assess the need for breathing coaching. It was demonstrated that the Sample Entropy metric was correlated to the irregularity of the patient’s respiratory motion in terms of periodicity, whilst other metrics, such as percentage deviation of inhale/exhale peak positions provided insight into respiratory amplitude regularity.     

A study of the effect of radiation on megakaryocytopoiesis using a mathematical model

Mathematical modelling used in analysing the postirradiation changes in megakaryocytopoiesis permitted to determine the level of radiation-induced injury in each experiment conducted and to show that megakaryocytopoiesis regulation followed the same mechanism after irradiation as it does normally and after the effect of hydroxyurea and anti-thrombocyte serum. The analysis has demonstrated that after the stem cell death induced by ionizing radiation, the regeneration can be provided by the committed cells, and the level of regeneration is determined by the maturity of precursors.     

On the interplay effect for moving targets treated with the CyberKnife static tracking system

PurposeTo assess the interplay effect amplitude between different planned MU distributions and respiratory patterns in the CyberKnife system when treating moving targets with static tracking technique.MethodsSmall- and Large-Respiratory Motions (SRM and LRM) differing in amplitude and frequency were simulated in a semi-anthropomorphic dynamic thorax phantom. The interplay effect was evaluated for both respiration motions in terms of GTV coverage and conformity for three plans designed with an increasing range of MU per beam (small, medium and large). Each plan was delivered three times changing the initial beam-on phase to assess the inter-fraction variation. Dose distributions were measured using radiochromic films placed in the GTV axial and sagittal planes.ResultsGenerally, SRM plans gave higher GTV coverage and were less dependent on beam-on phases than LRM plans. For SRM (LRM) plans, the GTV coverage ranged from 95.2% to 99.7% (85.9% to 99.8%). Maximum GTV coverage was found for large MU plans in SRM and for small MU plans in LRM. Minimum GTV coverage was found for medium MU plans for both SRM and LRM. For SRM plans, dose conformity decreased with increasing MU range while the variation was reduced for LRM plans. Large MU plans reduced the inter-fraction variation for SRM and LRM.ConclusionsWe confirmed the interplay effect between target motion and beam irradiation time for CyberKnife static tracking. Plans with large MU per beam improved the GTV coverage for small motion amplitude and the inter-fraction dose variation for large motion amplitude.     

The Adsorption of Argon and Nitrogen in Silicalite-1 Zeolite: A Grand Canonical Monte-Carlo study

Abstract

Grand Ensemble Monte-Carlo simulations of adsorption of argon and nitrogen in silicalite have been performed using a new adsorbate/zeolite potential function. In both cases, a good agreement with zero coverage data (Henry law constant and isosteric heat of adsorption) has been obtained. For argon, the simulated isotherm at 77 K exhibits the experimentally observed step. This is attributed to an in site/off-site phase transition of the adsorbed phase. The calculated neutron diffraction spectra are in reasonable agreement with those obtained experimentally. Furthermore, we suggest, in light of recent ⁴⁰Ar diffraction experiments of Tosi-Pellenq and Coulomb [18,44], that the shift in pressure between the simulated and the experimental isotherms corresponds to changes in the zeolite structure accompanied with the adsorbate phase transition itself. For nitrogen, only the first of the two experimentally observed steps is reproduced in the simulation. This step corresponds to an ordering of the adsorbed phase. The fact that the second step is missing in the simulated isotherm supports the hypothesis of a distortion of the zeolite framework under the stress of the adsorbed fluid at high loading.     

First-in-human imaging using a MR-compatible e4D ultrasound probe for motion management of radiotherapy

PurposeRespiration-induced tumor or organ positional changes can impact the accuracy of external beam radiotherapy. Motion management strategies are used to account for these changes during treatment. The authors report on the development, testing, and first-in-human evaluation of an electronic 4D (e4D) MR-compatible ultrasound probe that was designed for hands-free operation in a MR and linear accelerator (LINAC) environment.MethodsUltrasound components were evaluated for MR compatibility. Electromagnetic interference (EMI) shielding was used to enclose the entire probe and a factory-fabricated cable shielded with copper braids was integrated into the probe. A series of simultaneous ultrasound and MR scans were acquired and analyzed in five healthy volunteers.ResultsThe ultrasound probe led to minor susceptibility artifacts in the MR images immediately proximal to the ultrasound probe at a depth of <10 mm. Ultrasound and MR-based motion traces that were derived by tracking the salient motion of endogenous target structures in the superior-inferior (SI) direction demonstrated good concordance (Pearson correlation coefficients of 0.95–0.98) between the ultrasound and MRI datasets.ConclusionWe have demonstrated that our hands-free, e4D probe can acquire ultrasound images during a MR acquisition at frame rates of approximately 4 frames per second (fps) without impacting either the MR or ultrasound image quality. This use of this technology for interventional procedures (e.g. biopsies and drug delivery) and motion compensation during imaging are also being explored.     

Properties of star-branched and linear chains in confined space. A Monte-Carlo study

We have studied the properties of simple models of linear and star-branched polymer chains confined in a slit formed by two parallel impenetrable walls. The polymer chains consisted of identical united atoms (homopolymers) and were restricted to a simple cubic lattice. Two macromolecular architectures of the chain: linear and regular stars with three branches of equal length, were studied. The excluded volume was the only potential introduced into the model and thus the system was athermal. Monte-Carlo simulations with the sampling algorithm based on the chains local changes of conformation were carried out for chains with different lengths as well as for different distances between the confining surfaces. We found that the properties of model chains differ for both macromolecular architectures but a universal behavior for both kinds of chains was also found. Investigation of the frequency of chain-wall contacts shows that the ends of the chains are much more mobile than the rest of the chain, especially in the vicinity of the branching point in star polymers.Figure The scheme of a star-branched (left) and a linear (right) chain located between two parallel impenetrable surfaces.     

A visual patient feedback device using optical surface measurement for the cooperative management of setup and body dynamics during radiotherapy

In this technical note we describe a real-time visual feedback device for use during radiotherapy treatment. The device displays a patient's live pose and position, relative to a reference, to them, helping them to control and maintain their motion. The device uses an optical sensor system developed at The Christie NHS Foundation Trust that is capable of real-time performance of up to 24 unique wide-area body surface measurements per second. The feedback device has integrated audio and three intuitive visualisation modes designed to show different levels of detail with varying degrees of complexity: a ‘2D traffic-light display’, ‘3D flexing lamina display’ and ‘3D colour-mapped surface display’. The performance characteristics of the system were measured, with the frame rate, throughput and latency of the feedback device being 22.4 fps, 47.0 Mbps, 109.8 ms, and 13.7 fps, 86.4 Mbps, 119.1 ms for single and three-channel modes respectively. We additionally present a novel fast method for calculating the vertical displacement map of two 3D surfaces suitable for live, real time display and evaluate its precision with respect to other methodologies.     

Factors influencing the use of adaptive radiation therapy in vulvar carcinoma

AimWe aim to evaluate the variables affecting the frequency of adaptive radiotherapy (ART) in vulvar cancer.BackgroundART may be needed throughout a definitive RT course for vulvar carcinoma due to changes in patient’s anatomy and tumor response.Materials and methodsCharts of patients charts who had been treated with definitive concurrent chemo-radiotherapy for vulvar carcinoma, between January 2015 and December 2019 were inquired. Radiation therapy was delivered using intensity modulated radiotherapy (IMRT) with daily image-guided radiotherapy (IGRT). ART was defined as re-simulation and re-planning based on deformation in the irradiated volume by more than 1 cm. Univariate analysis was conducted to study the impact of patient’s demographics as well as tumor characteristics on the frequency of ART.Results22 patients were eligible for analysis. Median age at diagnosis was 55 years (range 43–82). Radiotherapy dose was 60−66 Gy over 30–35 fractions (fx). Median primary tumor volume was 30cc (9–140). Median Body Mass Index (BMI) was 32 (range 21–40). Thirteen out of 22 patients (59%) required ART, with median timing at 25 fx (19–31). On univariate analysis, larger primary tumor volume (> = 30cc) was associated significantly with increased frequency of ART (p value = 0.0005). There was no significant impact of ART on the frequency with respect to patient’s age, BMI, tumor stage, grade and location.ConclusionChanges in radiation target volume are common among vulvar carcinoma patients who are treated with definitive radiotherapy, especially large primary tumors. This review highlights the importance of ART for patients with vulvar carcinoma treated with definitive radiotherapy.     

Ultrasound tracking for intra-fractional motion compensation in radiation therapy

Modern techniques as ion beam therapy or 4D imaging require precise target position information. However, target motion particularly in the abdomen due to respiration or patient movement is still a challenge and demands methods that detect and compensate this motion. Ultrasound represents a non-invasive, dose-free and model-independent alternative to fluoroscopy, respiration belt or optical tracking of the patient surface. Thus, ultrasound based motion tracking was integrated into irradiation with actively scanned heavy ions. In a first in vitro experiment, the ultrasound tracking system was used to compensate diverse sinusoidal target motions in two dimensions. A time delay of ∼200 ms between target motion and reported position data was compensated by a prediction algorithm (artificial neural network). The irradiated films proved feasibility of the proposed method. Furthermore, a practicable and reliable calibration workflow was developed to enable the transformation of ultrasound tracking data to the coordinates of the treatment delivery or imaging system – even if the ultrasound probe moves due to respiration. A first proof of principle experiment was performed during time-resolved positron emission tomography (4DPET) to test the calibration workflow and to show the accuracy of an ultrasound based motion tracking in vitro. The results showed that optical ultrasound tracking can reach acceptable accuracies and encourage further research.     

The role of medical physics in prostate cancer radiation therapy

Medical physics, both as a scientific discipline and clinical service, hugely contributed and still contributes to the advances in the radiotherapy of prostate cancer. The traditional translational role in developing and safely implementing new technology and methods for better optimizing, delivering and monitoring the treatment is rapidly expanding to include new fields such as quantitative morphological and functional imaging and the possibility of individually predicting outcome and toxicity. The pivotal position of medical physicists in treatment personalization probably represents the main challenge of current and next years and needs a gradual change of vision and training, without losing the traditional and fundamental role of physicists to guarantee a high quality of the treatment. The current focus issue is intended to cover traditional and new fields of investigation in prostate cancer radiation therapy with the aim to provide up-to-date reference material to medical physicists daily working to cure prostate cancer patients. The papers presented in this focus issue touch upon present and upcoming challenges that need to be met in order to further advance prostate cancer radiation therapy. We suggest that there is a smart future for medical physicists willing to perform research and innovate, while they continue to provide high-quality clinical service. However, physicists are increasingly expected to actively integrate their implicitly translational, flexible and high-level skills within multi-disciplinary teams including many clinical figures (first of all radiation oncologists) as well as scientists from other disciplines.     

Tracheal cancer: Role of radiation therapy

Purpose

To assess the results of tracheal cancer patients treatment and factors influencing prognosis.

Background

Primary malignant neoplasms of the trachea are rare. The treatment of choice for tracheal carcinomas is resection. Radiation therapy is recommended as a part of radical treatment or for palliation of symptoms.

Materials and methods

Between 1962 and 2006, 50 patients diagnosed with tracheal cancer were treated at the Centre of Oncology in Krakow. The analysis focused on locoregional recurrence-free survival (LRRFS), disease free survival (DFS) and overall survival (OS). Survival rates, univariate and multivariate analyses of prognostic factors were performed using the Kaplan–Meier method, the log rank test and Cox''s proportional hazard method, respectively.For over 40 years, patients were treated using different modalities: surgery followed by radiotherapy (6%), radiotherapy (78%), chemoradiotherapy (8%), and symptomatic treatment (8%).

Results

The 5-year LRRFS was 18%, DFS was 15% and OS was 17%. gender (favoured females) was the only prognostic factor for LRRFS. For OS, the independent prognostic factors were performance status (favoured Karnofsky higher than 80), stage and year of start of the treatment (later than 1988 vs. earlier – 5-year OS 20% vs. 12%).5-year OS in the following (strongly differentiated over the time) treatment modalities were: surgery followed by radiotherapy (66%), radiotherapy (16%), chemoradiotherapy (0%), and symptomatic treatment (0%).Of 44 patients treated with radiotherapy symptomatic partial response was observed in 32 patients and follow-up imaging studies revealed complete response in 5 patients, partial response in 25, stable disease in 4 or progressive disease in 4.

Conclusions

Radical treatment in patients in early stage and good performance status seems to be correlated with the improvement of survival. However, despite the fact that results of treatment are poor, radiotherapy offers symptomatic improvement.     

Study of dental prostheses influence in radiation therapy

Dental prostheses made of high density material contribute to modify dose distribution in head and neck cancer treatment. Our objective is to quantify dose perturbation due to high density inhomogeneity with experimental measurements and Monte Carlo simulations.Firstly, measurements were carried in a phantom representing a human jaw with thermoluminescent detectors (GR200A) and EBT2 Gafchromic films in the vicinity of three samples: a healthy tooth, a tooth with amalgam and a Ni–Cr crown, irradiated in clinical configuration. Secondly, Monte Carlo simulations (BEAMnrc code) were assessed in an identical configuration.Experimental measurements and simulation results confirm the two well-known phenomena: firstly the passage from a low density medium to a high density medium induces backscattered electrons causing a dose increase at the interface, and secondly, the passage from a high density medium to a low density medium creates a dose decrease near the interface. So, the results show a 1.4% and 23.8% backscatter dose rise and attenuation after sample of 26.7% and 10.9% respectively for tooth with amalgam and crown compared to the healthy tooth.Although a tooth with amalgam has a density of about 12–13, the changes generated are not significant. However, the results for crown (density of 8) are very significant and the discordance observed may be due to calculation point size difference 0.8 mm and 0.25 mm respectively for TLD and Monte Carlo. The use of Monte Carlo simulations and experimental measurements provides objective evidence to evaluate treatment planning system results with metal dental prostheses.     

A Bayesian mixture model relating dose to critical organs and functional complication in 3D conformal radiation therapy

A goal of cancer radiation therapy is to deliver maximum dose to the target tumor while minimizing complications due to irradiation of critical organs. Technological advances in 3D conformal radiation therapy has allowed great strides in realizing this goal; however, complications may still arise. Critical organs may be adjacent to tumors or in the path of the radiation beam. Several mathematical models have been proposed that describe the relationship between dose and observed functional complication; however, only a few published studies have successfully fit these models to data using modern statistical methods which make efficient use of the data. One complication following radiation therapy of head and neck cancers is the patient's inability to produce saliva. Xerostomia (dry mouth) leads to high susceptibility to oral infection and dental caries and is, in general, unpleasant and an annoyance. We present a dose-damage-injury model that subsumes any of the various mathematical models relating dose to damage. The model is a nonlinear, longitudinal mixed effects model where the outcome (saliva flow rate) is modeled as a mixture of a Dirac measure at zero and a gamma distribution whose mean is a function of time and dose. Bayesian methods are used to estimate the relationship between dose delivered to the parotid glands and the observational outcome-saliva flow rate. A summary measure of the dose-damage relationship is modeled and assessed by a Bayesian chi(2) test for goodness-of-fit.     

Choosing between conventional and hypofractionated prostate cancer radiation therapy: Results from a study of shared decision-making

AimTo evaluate patient choice of prostate cancer radiotherapy fractionation, using a decision aid.BackgroundRecent ASTRO guidelines recommend patients with localised prostate cancer be offered moderately hypofractionated radiation therapy after discussing increased acute toxicity and uncertainty of long-term results compared to conventional fractionation.Materials and methodsA decision aid was designed to outline the benefits and potential downsides of conventionally and moderately hypofractionated radiation therapy. The aid incorporated the ASTRO guideline to outline risks and benefits.ResultsIn all, 124 patients with localised prostate cancer were seen from June-December 2018. Median age was 72 (range 50–90), 49.6 % were intermediate risk (50.4 % high risk). All except three patients made a choice using the aid; the three undecided patients were hypofractionated. In all, 33.9 % of patients chose hypofractionation: falling to 25.3 % for patients under 75 years, 24.3 % for patients living within 30 miles of the cancer centre, and 14.3 % for patients with baseline gastrointestinal symptoms. On multivariate analysis, younger age, proximity to the centre, and having baseline gastrointestinal symptoms significantly predicted for choosing conventional fractionation. Insurance status, attending clinician, baseline genitourinary symptoms, work/carer status, ECOG, cancer risk group and driving status did not impact choice. Reasons for choosing conventional fractionation were certainty of long-term results (84 %) and lower acute bowel toxicity (51 %).ConclusionsMost patients declined the convenience of moderate hypofractionation due to potentially increased acute toxicity, and the uncertainty of long-term outcomes. We advocate that no patient should be offered hypofractionation without a thorough discussion of uncertainty and acute toxicity.     

Skin barrier function in patients under radiation therapy due to the head and neck cancers - Preliminary study

AimTo present the possibility of non-invasive monitoring of the skin after radiotherapy in regards of epidermal barrier function.BackgroundRadiodermatitis constitutes 95% of all side effects in patients after radiotherapy. The proper assessment of the severity of radiodermatitis can be determined using semi-quantitative clinical scores [Common Terminology Criteria for Adverse Events v 4.0 (CTCAE)].The most accepted way to analyze the epidermal barrier function is to determine Transepidermal Water Loss (TEWL).Material and methodsIn prospective study, we included 16 patients diagnosed with head and neck cancer treated with radiotherapy or concomitant chemoradiation in whom we performed non-invasive assessments of the skin barrier function, including TEWL measurement. The final analysis included 6 patients (4 treated with adjuvant radiotherapy, 2 with radical chemoradiation). Clinical assessment of irradiated skin was based on target lesion score (TLS) and CTCAE v 4.0ResultsThe mean TLS score in the middle of irradiation was 1.6 points, after last irradiation it was 2.3 points; 3 months later the mean TLS score was: 0. CTCAE v 4.0 criteria: 2 patients had grade 0, 3 patients - grade 1; 1 patient - grade 2. There were statistically significant differences in TEWL related to irradiated skin in the following time intervals: before vs. in the middle; before vs. day after; in the middle vs. day after; in the middle vs. 3 months after; day after vs. 3 months after.ConclusionsThe study showed that radiotherapy causes skin barrier dysfunction in all patients independently of clinical radiodermatitis. The biophysical features of this dysfunction can precede clinical symptoms and they can be assessed by non-invasive and objective methods.     

Enhanced dermatologic toxicity following concurrent treatment with palbociclib and radiation therapy: A case report

BackgroundCyclin-dependent kinase (CDK) 4/6 inhibitors represent a new class of targeted therapy options for the treatment of estrogen receptor-positive (ER+) human epidermal growth factor 2-negative (HER2-) metastatic breast cancer. There are currently no published prospective data on the safety of use of radiation treatment with palbociclib.CaseWe describe the case of a patient with metastatic breast cancer who received radiation treatment to a metastatic supraclavicular lymph node to planned 60 Gy in 30 fractions while on palbociclib, a selective inhibitor of CDK4/6. The patient developed early radiation toxicities including esophagitis and dermatitis that progressed to a severe left neck skin breakdown in the radiation field, resulting in the need for hospitalization. She had a break in treatment but was able to finish the radiation without palbociclib. Her tumor responded well to the treatment and her side effects healed.DiscussionTo our knowledge this is the first case to report on concurrent palbociclib and radiation use, with resultant enhanced radiation effects that required hospitalization for symptom management. Several preclinical studies have shown synergistic effects of radiation and both in vivo and in vitro experiments resulting in improved survival and decreased cell proliferation, respectively, through enhanced G1 cell cycle arrest.ConclusionThis case highlights the importance of using caution when combining radiation with the new targeted therapies. Until more data becomes available, physicians are recommended to exercise clinical judgment when deciding on whether to continue or discontinue a CDK4/6 inhibitor in a patient who may need radiation.     

A study of the viscoelastic effect in a bone remodeling model

The present paper addresses the following question can a simple regulatory bone remodeling model predict effects of viscosity on the trabecular morphology? For that, we propose an extension of a previous bone remodeling model by taking into account the viscosity properties of the tissue. Zener’s law is used to describe the mechanical behavior of the bone and a specific law of the apparent bone density rate is proposed. Based on stability analysis, numerical simulations are then performed to investigate the viscosity role on simulations of the bone remodeling process. We show that the viscous contribution affects the evolution of the apparent bone density, by slowing down the adaptation process, which seems to be confirmed by simulations with real data obtained from rat tibia.