Eva Bezak

Monte Carlo investigation of the increased radiation deposition due to gold nanoparticles using kilovoltage and megavoltage photons in a 3D randomized cell model

PURPOSE Investigation of increased radiation dose deposition due to gold nanoparticles (GNPs) using a 3D computational cell model during x-ray radiotherapy. METHODS Two GNP simulation scenarios were set up in Geant4; a single 400 nm diameter gold cluster randomly positioned in the cytoplasm and a 300 nm gold layer around the nucleus of the cell. Using an 80 kVp photon beam, the effect of GNP on the dose deposition in five modeled regions of the cell including cytoplasm, membrane, and nucleus was simulated. Two Geant4 physics lists were tested: the default Livermore and custom built Livermore/DNA hybrid physics list. 10(6) particles were simulated at 840 cells in the simulation. Each cell was randomly placed with random orientation and a diameter varying between 9 and 13 μm. A mathematical algorithm was used to ensure that none of the 840 cells overlapped. The energy dependence of the GNP physical dose enhancement effect was calculated by simulating the dose deposition in the cells with two energy spectra of 80 kVp and 6 MV. The contribution from Auger electrons was investigated by comparing the two GNP simulation scenarios while activating and deactivating atomic de-excitation processes in Geant4. RESULTS The physical dose enhancement ratio (DER) of GNP was calculated using the Monte Carlo model. The model has demonstrated that the DER depends on the amount of gold and the position of the gold cluster within the cell. Individual cell regions experienced statistically significant (p < 0.05) change in absorbed dose (DER between 1 and 10) depending on the type of gold geometry used. The DER resulting from gold clusters attached to the cell nucleus had the more significant effect of the two cases (DER ≈ 55). The DER value calculated at 6 MV was shown to be at least an order of magnitude smaller than the DER values calculated for the 80 kVp spectrum. Based on simulations, when 80 kVp photons are used, Auger electrons have a statistically insignificant (p < 0.05) effect on the overall dose increase in the cell. The low energy of the Auger electrons produced prevents them from propagating more than 250-500 nm from the gold cluster and, therefore, has a negligible effect on the overall dose increase due to GNP. CONCLUSIONS The results presented in the current work show that the primary dose enhancement is due to the production of additional photoelectrons.

Review of MammoSite brachytherapy: Advantages, disadvantages and clinical outcomes

Background. The MammoSite® radiotherapy system is an alternative treatment option for patients with early-stage breast cancer to overcome the longer schedules associated with external beam radiation therapy. The device is placed inside the breast surgical cavity and inflated with a combination of saline and radiographic contrast to completely fill the cavity. The treatment schedule for the MammoSite monotherapy is 34 Gy delivered in 10 fractions at 1.0 cm from the balloon surface with a minimum of 6 hours between fractions on the same day. Material and methods. This review article presents the advantages, disadvantages, uncertainties and clinical outcomes associated with the MammoSite brachytherapy (MSB). Results. Potential advantages of MSB are: high localised dose with rapid falloff for normal tissue sparing, minimum delay between surgery and RT, catheter moves with breast, improved local control, no exposure to staff, likely side-effects reduction and potential cost/time saving (e.g. for country patients). The optimal cosmetic results depend on the balloon-to-skin distance. Good-to-excellent cosmetic results are achieved for patients with balloon-skin spacing of ≥7 mm. There have been very few published data regarding the long term tumour control and cosmesis associated with the MSB. The available data on the local control achieved with the MSB were comparable with other accelerated partial breast irradiation techniques. The contrast medium inside the balloon causes dose reduction at the prescription point. Current brachytherapy treatment planning systems (BTPS) do not take into account the increased photon attenuation due to high Z of contrast. Some BTPS predicted up to 10% higher dose near the balloon surface compared with Monte Carlo calculations using various contrast concentrations (5–25%). Conclusion. Initial clinical results have shown that the MammoSite device could be used as a sole radiation treatment for selected patients with early stage breast cancer providing good local control, minimal complication rate and excellent cosmesis.

Out-of-Field Neutron and Leakage Photon Exposures and the Associated Risk of Second Cancers in High-Energy Photon Radiotherapy: Current Status

Determination and understanding of out-of-field neutron and photon doses in accelerator-based radiotherapy is an important issue since linear accelerators operating at high energies (>10 MV) produce secondary radiations that irradiate parts of the patients anatomy distal to the target region, potentially resulting in detrimental health effects. This paper provides a compilation of data (technical and clinical) reported in the literature on the measurement and Monte Carlo simulations of peripheral neutron and photon doses produced from high-energy medical linear accelerators and the reported risk and/or incidence of second primary cancer of tissues distal to the target volume. Information in the tables facilitates easier identification of (1) the various methods and measurement techniques used to determine the out-of-field neutron and photon radiations, (2) reported linac-dependent out-of-field doses, and (3) the risk/incidence of second cancers after radiotherapy due to classic and modern treatment methods. Regardless of the measurement technique and type of accelerator, the neutron dose equivalent per unit photon dose ranges from as low as 0.1 mSv/Gy to as high as 20.4 mSv/Gy. This radiation dose potentially contributes to the induction of second primary cancer in normal tissues outside the treated area.

Risk of second primary cancer following prostate cancer radiotherapy: DVH analysis using the competitive risk model

This study aimed to estimate the risk of developing second primary cancer (SPC) corresponding to various radiation treatment techniques for prostate cancer. Estimation of SPC was done by analysing differential dose-volume histograms (DDVH) of normal tissues such as rectum, bladder and urethra with the competitive risk model. Differential DVHs were obtained from treatment planning systems for external beam radiotherapy (EBRT), low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy techniques. The average risk of developing SPC was no greater than 0.6% for all treatment techniques but was lower with either LDR or HDR brachytherapy alone compared with any EBRT technique. For LDR and HDR brachytherapy alone, the risk of SPC for the rectum was 2.0 x 10(-4)% and 8.3 x 10(-5)% respectively compared with 0.2% for EBRT using five-field 3D-CRT to a total dose of 74 Gy. Overall, the risk of developing SPC for urethra following all radiation treatment techniques was very low compared with the rectum and bladder. Treatment plans which deliver equivalent doses of around 3-5 Gy to normal tissues were associated with higher risks of development of SPC.

Four dimensional CT imaging: a review of current technologies and modalities

Organ motion is a substantial concern in the treatment of thoracic tumours using radiotherapy. A number of technologies have evolved in order to address this both during computed tomography (CT) imaging and radiation delivery. This review paper investigates the various technologies which have been developed in the field of CT scanning as well as their accuracy, cost and the implications of their clinical implementation. The scanning modalities covered include: slow CT, breath hold CT, gated CT and retrospectively correlated CT (4DCT). It was found that there are advantages and drawbacks to each of the mentioned techniques relating to patient dose, scan time, extra equipment and workload. Also some scanning techniques are only compatible with certain treatment modalities which would further influence the decision as to which technologies to implement.

Review of Geant4-DNA applications for micro and nanoscale simulations

Emerging radiotherapy treatments including targeted particle therapy, hadron therapy or radiosensitisation of cells by high-Z nanoparticles demand the theoretical determination of radiation track structure at the nanoscale. This is essential in order to evaluate radiation damage at the cellular and DNA level. Since 2007, Geant4 offers physics models to describe particle interactions in liquid water at the nanometre level through the Geant4-DNA Package. This package currently provides a complete set of models describing the event-by-event electromagnetic interactions of particles with liquid water, as well as developments for the modelling of water radiolysis. Since its release, Geant4-DNA has been adopted as an investigational tool in kV and MV external beam radiotherapy, hadron therapies using protons and heavy ions, targeted therapies and radiobiology studies. It has been benchmarked with respect to other track structure Monte Carlo codes and, where available, against reference experimental measurements. While Geant4-DNA physics models and radiolysis modelling functionalities have already been described in detail in the literature, this review paper summarises and discusses a selection of representative papers with the aim of providing an overview of a) geometrical descriptions of biological targets down to the DNA size, and b) the full spectrum of current micro- and nano-scale applications of Geant4-DNA.

Non-targeted effects of ionising radiation and radiotherapy

Modern radiobiology is undergoing rapid change due to new discoveries contradicting the target concept which is currently used to predict dose–response relationships. Thus relatively recently discovered radiation-induced bystander effects (RIBEs), that include additional death, mutation and radio-adaptation in non-irradiated cells, change our understanding of the target concept and broadens its boundaries. This can be significant from a radioprotection point of view and also has the potential to reassess radiation damage models currently used in radiotherapy. This article reviews briefly the general concepts of RIBEs such as the proposed underlying mechanisms of signal induction and propagation, experimental approaches and biological end points used to investigate these phenomena. It also summarises several mathematical models currently proposed in an attempt to quantify RIBE. The main emphasis of this article is to review and highlight the potential impact of the bystander phenomena in radiotherapy.

Monte Carlo radiotherapy simulations of accelerated repopulation and reoxygenation for hypoxic head and neck cancer

OBJECTIVE A temporal Monte Carlo tumour growth and radiotherapy effect model (HYP-RT) simulating hypoxia in head and neck cancer has been developed and used to analyse parameters influencing cell kill during conventionally fractionated radiotherapy. The model was designed to simulate individual cell division up to 10(8) cells, while incorporating radiobiological effects, including accelerated repopulation and reoxygenation during treatment. METHOD Reoxygenation of hypoxic tumours has been modelled using randomised increments of oxygen to tumour cells after each treatment fraction. The process of accelerated repopulation has been modelled by increasing the symmetrical stem cell division probability. Both phenomena were onset immediately or after a number of weeks of simulated treatment. RESULTS The extra dose required to control (total cell kill) hypoxic vs oxic tumours was 15-25% (8-20 Gy for 5 × 2 Gy per week) depending on the timing of accelerated repopulation onset. Reoxygenation of hypoxic tumours resulted in resensitisation and reduction in total dose required by approximately 10%, depending on the time of onset. When modelled simultaneously, accelerated repopulation and reoxygenation affected cell kill in hypoxic tumours in a similar manner to when the phenomena were modelled individually; however, the degree was altered, with non-additive results. Simulation results were in good agreement with standard linear quadratic theory; however, differed for more complex comparisons where hypoxia, reoxygenation as well as accelerated repopulation effects were considered. CONCLUSION Simulations have quantitatively confirmed the need for patient individualisation in radiotherapy for hypoxic head and neck tumours, and have shown the benefits of modelling complex and dynamic processes using Monte Carlo methods.

Two-dimensional transmitted dose measurements using a scanning liquid ionization chamber EPID

The use of a scanning liquid ionization chamber electronic portal imaging device (SLIC-EPID) for two-dimensional transmitted dosimetry was investigated and a calibration method was developed using extended dose range (EDR2) film. In order to convert pixel value to dose, the acquired SLIC-EPID pixel values were calibrated using an ionization chamber on the central axis. The relationship between pixel values, dose rate and absorbed dose was identified for various linac output repetition rates. To correct EPIs for dosimetric purposes, the off-axis ratio of dose profiles measured by EPIDs and EDR2 film was used to derive correction factor matrices (CFMs) for a range of source-to-EPID distances (SEDs). The corrected relative dose maps acquired for different conditions, including open and wedged fields, measured using a SLIC-EPID were compared with EDR2 film images using a gamma function algorithm with distance to agreement (DTA) = 2.5 mm and dose difference (DeltaDmax) = 1% criteria. The results showed that (a) for two-dimensional dosimetric purposes, EPIDs must be calibrated using appropriate two-dimensional correction factors and (b) SLIC-EPIDs can be used to measure the transmitted dose with good accuracy.

Assessment of flatness and symmetry of megavoltage x-ray beam with an electronic portal imaging device (EPID)

The input/output characteristics of the Wellhofer BIS 710 electronic portal imaging device (EPID) have been investigated to establish its efficacy for periodic quality assurance (QA) applications. Calibration curves have been determined for the energy fluence incident on the detector versus the pixel values. The effect of the charge coupled device (CCD) camera sampling time and beam parameters (such as beam field size, dose rate, photon energy) on the calibration have been investigated for a region of interest (ROI) around the central beam axis. The results demonstrate that the pixel output is a linear function of the incident exposure, as expected for a video-based electronic portal imaging system. The field size effects of the BIS 710 are similar to that of an ion chamber for smaller field sizes up to 10 x 10 cm2. However, for larger field sizes the pixel value increases more rapidly. Furthermore, the system is slightly sensitive to dose rate and is also energy dependent. The BIS 710 has been used in the current study to develop a QA procedure for measurements of flatness and symmetry of a linac x-ray beam. As a two-dimensional image of the radiation field is obtained from a single exposure of the BIS 710, a technique has been developed to calculate flatness and symmetry from a defined radiation area. The flatness and symmetry values obtained are different from those calculated conventionally from major axes only (inplane, crossplane). This demonstrates that the technique can pick up the “cold” and “hot” spots in the analysed area, providing thus more information about the radiation beam. When calibrated against the water tank measurements, the BIS 710 can be used as a secondary device to monitor the x-ray beam flatness and symmetry.