Implementation of a dose gradient method into optimization of dose distribution in prostate cancer 3D-CRT plans

AimThe aim of this work is to present a method of beam weight and wedge angle optimization for patients with prostate cancer.Background3D-CRT is usually realized with forward planning based on a trial and error method. Several authors have published a few methods of beam weight optimization applicable to the 3D-CRT. Still, none on these methods is in common use.Materials and methodsOptimization is based on the assumption that the best plan is achieved if dose gradient at ICRU point is equal to zero. Our optimization algorithm requires beam quality index, depth of maximum dose, profiles of wedged fields and maximum dose to femoral heads. The method was tested for 10 patients with prostate cancer, treated with the 3-field technique. Optimized plans were compared with plans prepared by 12 experienced planners. Dose standard deviation in target volume, and minimum and maximum doses were analyzed.ResultsThe quality of plans obtained with the proposed optimization algorithms was comparable to that prepared by experienced planners. Mean difference in target dose standard deviation was 0.1% in favor of the plans prepared by planners for optimization of beam weights and wedge angles. Introducing a correction factor for patient body outline for dose gradient at ICRU point improved dose distribution homogeneity. On average, a 0.1% lower standard deviation was achieved with the optimization algorithm. No significant difference in mean dose–volume histogram for the rectum was observed.ConclusionsOptimization shortens very much time planning. The average planning time was 5 min and less than a minute for forward and computer optimization, respectively.     

A generic method of pesticide dose expression: Application to broadcast spraying of apple trees

The recommended dose for many pesticides is expressed as a constant mass or volume per unit ground area covered by the crop. This method of dose expression is well suited to boom spraying where a reasonably uniform horizontal distribution of deposit can be achieved with a well‐adjusted sprayer. However, in many practical situations (e.g. broadcast spraying of apple trees or other row structures where the spray application is made from within the canopy) the horizontal deposit distribution is strongly influenced by the crop area density and other crop structural parameters. This paper describes a generic method of pesticide dose expression to investigate these effects. The method incorporates a model of the spray volume deposition process. The model assumes that the pesticide deposit is proportional to the tank‐mix concentration of pesticide. The model also assumes that spray volume deposit is proportional to the applied spray volume per unit row length and is inversely proportional to a crop length scaling function L (i.e. a parameter with the units of length that is expressed as a generic function of different crop parameters). The useful working range of this model is bounded by the condition for high spray volume where target losses become significant due to saturation and the condition for very low volume where evaporative transport losses become significant. Within this framework, four different models are formulated using first‐order approximations for the length‐scale as functions of the following crop parameters: tree row spacing, tree row height, tree area density and tree row volume to ground area ratio. Published measurements of crop structure and spray volume deposit on apple trees are compared with the output from these models. Light detection and range (LIDAR) measurements of apple orchards are presented and used in conjunction with the different models to predict pesticide use associated with different methods of dose expression. The results demonstrate the relative potential for varying the pesticide application rate according to the different crop parameters. The results enable the identification of reference orchards that could be used to establish worst‐case pesticide application rates for registration purposes. The results also enable the identification of other orchards and growth stages where pesticide application rate might be reduced by up to a factor of five and give the same pesticide deposit as the reference structure.     

Statistical models for low dose exposure

Extrapolation of health risks from high to low doses has received a considerable amount of attention in carcinogenic risk assessment over decades. Fitting statistical dose-response models to experimental data collected at high doses and use of the fitted model for estimating effects at low doses lead to quite different risk predictions. Dissatisfaction with this procedure was formulated both by toxicologists who saw a deficit of biological knowledge in the models as well as by risk modelers who saw the need of mechanistically-based stochastic modeling. This contribution summarizes the present status of low dose modeling and the determination of the shape of dose-response curves. We will address the controversial issues of the appropriateness of threshold models, the estimation of no observed adverse effect levels (NOAEL), and their relevance for low dose modeling. We will distinguish between quantal dose-response models for tumor incidence and models of the more informative age/time dependent tumor incidence. The multistage model and the two-stage model of clonal expansion are considered as dose-response models accounting for biological mechanisms. Problems of the identifiability of mechanisms are addressed, the relation between administered dose and effective target dose is illustrated by examples, and the recently proposed Benchmark Dose concept for risk assessment is presented with its consequences for mechanistic modeling and statistical estimation.     

Using electron beam radiation to simulate the dose distribution for whole body solar particle event proton exposure

As a part of the near solar system exploration program, astronauts may receive significant total body proton radiation exposures during a solar particle event (SPE). In the Center for Acute Radiation Research (CARR), symptoms of the acute radiation sickness syndrome induced by conventional radiation are being compared to those induced by SPE-like proton radiation, to determine the relative biological effectiveness (RBE) of SPE protons. In an SPE, the astronaut’s whole body will be exposed to radiation consisting mainly of protons with energies below 50 MeV. In addition to providing for a potentially higher RBE than conventional radiation, the energy distribution for an SPE will produce a relatively inhomogeneous total body dose distribution, with a significantly higher dose delivered to the skin and subcutaneous tissues than to the internal organs. These factors make it difficult to use a ⁶⁰Co standard for RBE comparisons in our experiments. Here, the novel concept of using megavoltage electron beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation is described. In these studies, Monte Carlo simulation was used to determine the dose distribution of electron beam radiation in small mammals such as mice and ferrets as well as large mammals such as pigs. These studies will help to better define the topography of the time-dose-fractionation versus biological response landscape for astronaut exposure to an SPE.     

The radiation dose to cells in vitro from intracellular indium-111

Most of the radionuclides used in nuclear medicine emit low energy Auger electrons following radioactive decay. These emissions, if intracellular, could irreparably damage the radiosensitive structures of the cell. The resulting radiation dose, which is a measure of biological damage in the affected cell, could be many times the average radiation dose to the associated organ. In this series of experiments, the radiation dose to the nucleus of a chinese hamster V79 cell was determined for the intracellular radiopharmaceutical 111indium-oxine. Assuming the cell nucleus to be the radiosensitive volume, the radiation dose would be primarily due to the low energy Auger electrons. A much smaller dose would be absorbed from the penetrating X- and gamma-rays and internal conversion electrons released from other radiolabelled cells in the culture. The radiation dose to the cell from the intranuclear decay of 111In was empirically established from cell survival studies to be 3.5 mGy/decay, using cobalt-60 as a reference radiation. The average dose to V79 cells from extracellular 111In (i.e., from 111In located outside the target cell) was calculated to be 5.8 pGy/decay. This suggests that for an intracellular radiopharmaceutical, the radiation dose of consequence would be delivered by the low energy Auger electrons. In contrast, Auger electrons from an extracellular radiopharmaceutical could not directly damage the cell nucleus and therefore would not contribute to the radiation dose.     

Quantitative analysis of biological responses to ionizing radiation, including dose, irradiation time, and dose rate

Because biological responses to radiation are complex processes that depend on both irradiation time and total dose, consideration of both dose and dose rate is necessary to predict the risk from long-term irradiations at low dose rates. Here we mathematically and statistically analyzed the quantitative relationships between dose, dose rate and irradiation time using micronucleus formation and inhibition of proliferation of human osteosarcoma cells as indicators of biological response. While the dose-response curves did not change with exposure times of less than 20 h, at a given dose, both biological responses clearly were reduced as exposure time increased to more than 8 days. These responses became dependent on dose rate rather than on total dose when cells were irradiated for 20 to 27 days. Mathematical analysis demonstrates that the relationship between effective dose and dose rate is well described by an exponential function when the logarithm of effective dose is plotted as a function of the logarithm of dose rate. These results suggest that our model, the modified exponential (ME) model, can be applied to predict the risk from exposure to low-dose/low-dose-rate radiation.     

Radiotherapy instead of axillary lymph node dissection: evaluation of axillary lymph node dose coverage with whole breast radiotherapy

BackgroundThe purpose of this study was to investigate the dose coverage of sentinel lymph nodes (SLN), level I, II and III axillary volumes from tangent fields for breast cancer patients with positive SLN without axillary dissection.Materials and methodsIn 30 patients with cN0 invasive breast cancer treated with breast conserving surgery and SLN biopsy, the SLN area was intraoperatively marked with a titanium clip. Retrospectively, the SLN area and axillary target volumes were contoured, and three plans [standard tangent fields (STgF), high tangent fields (HTgF), and STgF + axillary-supraclavicular field] were generated for each patient. The prescribed dose was standardized to 50 Gy in 2 Gy fractions to the isocenter.ResultsThe mean dose with STgF or HTgF was 33.1 and 49.1 Gy (p = 0.0001) in the SLN area, 25.7 and 45.1 Gy (p < 0.0001) in the volume of level I, 7.2 and 28.9 Gy (p < 0.0001) in the level II and 3.5 and 12.7 Gy (p = 0.0003) in the level III. Adequate therapeutic doses to the level II or III volumes were delivered only with STgF + axillary-supraclavicular field. The mean dose of ipsilateral lung was the highest with the three-field-technique, 9.9 Gy. SLN area, level I, II or III were completely included in the HTgF with 93.3%, 73.3%, 13.3% and 0%, respectively.ConclusionsSLN area should be marked by surgical clip and axillary target volumes should be contoured to obtain accurate dose estimations. The use of HTgF improve axillary coverage.     

Point-source irradiation with eccentric rotation causes inhomogeneous dose distribution

Radioactive point sources are regularly used for irradiating cell culture and other biological materials. Eccentric rotation is often used to minimize dose disparities that arise from irradiating samples that span a distance from the point source. Rotation provides a great improvement in dose homogeneity compared to inert irradiation yet still presents an obvious shortcoming for exposures in which the sample completes only partial rotation or fractional rotation. In such cases, certain areas of the sample have a closer average distance to the radiation source than other areas within the same sample. This obstacle can be partially overcome by adjusting rotation speed so the sample traverses a full rotation (or multiple thereof) throughout the total irradiation time. Here we investigate the effects of irradiation with eccentric rotation on dose homogeneity. We show that due to the inverse square law that governs dose, even exposures with full rotation result in inhomogeneous dose distributions. This dose inhomogeneity can be substantial, especially for large samples and small source- sample distances. We observed a 33% difference in survival across 100-mm dishes and a 400% difference for 150-mm dishes. The dose inhomogeneity inherent to eccentric rotation increases the actual average dose delivered across the sample compared to that delivered at sample center. We offer a table of correction factors that account for this dose increase and correct the dose delivered at center to the actual average dose delivered across the entire sample.     

Simulation and measurement of microbeam dose distribution in lung tissue

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

Equivalent uniform dose concept evaluated by theoretical dose volume histograms for thoracic irradiation

Background and PurposeThe goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application.Materials and MethodsWe focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH.ResultsWe evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation.ConclusionWe concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot–cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.     

Experimental assessment of proton dose calculation accuracy in inhomogeneous media

PurposeProton therapy with Pencil Beam Scanning (PBS) has the potential to improve radiotherapy treatments. Unfortunately, its promises are jeopardized by the sensitivity of the dose distributions to uncertainties, including dose calculation accuracy in inhomogeneous media. Monte Carlo dose engines (MC) are expected to handle heterogeneities better than analytical algorithms like the pencil-beam convolution algorithm (PBA). In this study, an experimental phantom has been devised to maximize the effect of heterogeneities and to quantify the capability of several dose engines (MC and PBA) to handle these.MethodsAn inhomogeneous phantom made of water surrounding a long insert of bone tissue substitute (1 × 10 × 10 cm³) was irradiated with a mono-energetic PBS field (10 × 10 cm²). A 2D ion chamber array (MatriXX, IBA Dosimetry GmbH) lied right behind the bone. The beam energy was such that the expected range of the protons exceeded the detector position in water and did not attain it in bone. The measurement was compared to the following engines: Geant4.9.5, PENH, MCsquare, as well as the MC and PBA algorithms of RayStation (RaySearch Laboratories AB).ResultsFor a γ-index criteria of 2%/2 mm, the passing rates are 93.8% for Geant4.9.5, 97.4% for PENH, 93.4% for MCsquare, 95.9% for RayStation MC, and 44.7% for PBA. The differences in γ-index passing rates between MC and RayStation PBA calculations can exceed 50%.ConclusionThe performance of dose calculation algorithms in highly inhomogeneous media was evaluated in a dedicated experiment. MC dose engines performed overall satisfactorily while large deviations were observed with PBA as expected.     

Implementation of a dose calculation algorithm based on Monte Carlo simulations for treatment planning towards MRI guided ion beam therapy

Magnetic resonance guidance in particle therapy has the potential to improve the current performance of clinical workflows. However, the presence of magnetic fields challenges the current algorithms for treatment planning. To ensure proper dose calculations, compensation methods are required to guarantee that the maximum deposited energy of deflected beams lies in the target volume. In addition, proper modifications of the intrinsic dose calculation engines, accounting for magnetic fields, are needed. In this work, an algorithm for proton treatment planning in magnetic fields was implemented in a research treatment planning system (TPS), matRad. Setup-specific look up tables were generated using a validated MC model for a clinical proton beamline (62.4 – 215.7 MeV) interacting with a dipole magnet (B = 0–1 T). The algorithm was successfully benchmarked against MC simulations in water, showing gamma index (2%/2mm) global pass rates higher than 96% for different plan configurations. Additionally, absorbed depth doses were compared with experimental measurements in water. Differences within 2% and 3.5% in the Bragg peak and entrance regions, respectively, were found. Finally, treatment plans were generated and optimized for magnetic field strengths of 0 and 1 T to assess the performance of the proposed model. Equivalent treatment plans and dose volume histograms were achieved, independently of the magnetic field strength. Differences lower than 1.5% for plan quality indicators (D_2%, D_50%, D_90%, V_95% and V_105%) in water, a TG119 phantom and an exemplary prostate patient case were obtained. More complex treatment planning studies are foreseen to establish the limits of applicability of the proposed model.     

Radiation dose detection by imaging response in biological targets

Imaging was one of the earliest techniques to quantify radiation dose. While films and active fluorescent detectors are still commonly used in physical dosimetry, biological imaging is emerging as a new method to visualize and quantify radiation dose in biological targets. Methods for biological imaging are normally based on molecular fluorescent probes, labeling chromatin-conjugated molecules or specific repair proteins. Examples are chromatin-binding coumarin compounds, which become fluorescent under irradiation, or the H2AX histone, which is rapidly phosphorylated at sites of DNA double-strand breaks and can be visualized by immunostaining. Many other DNA repair proteins can be expressed with fluorescent targets, such as green fluorescent protein, thus becoming visible for dose estimation in vivo. The possibility to visualize radiation damage in living biological targets is particularly important for repair kinetic studies, for estimating individual radiation response, and for remote control of living samples exposed to radiation, for instance in robotic space missions. In vivo dose monitoring in particle therapy exploits the production of positron emitters by nuclear interaction of the incident beam in the patient's body. Positron emission tomography (PET) can then be used to visualize and quantify the particle dose in the patient, and it can in principle also be used for radiotherapy with high-energy X rays. Alternatively, prompt γ rays or scattered secondary particles are under study for in vivo dosimetry of ion beams in therapy.     

Improved biological dosimetric margin model for different PTV margins with stereotactic body radiation therapy in homogeneous and nonhomogeneous tumor regions

BackgroundThe purpose of this study was to improve the biological dosimetric margin (BDM) corresponding to different planning target volume (PTV) margins in homogeneous and nonhomogeneous tumor regions using an improved biological conversion factor (BCF) model for stereotactic body radiation therapy (SBRT).Materials and methodsThe PTV margin was 5–20 mm from the clinical target volume. The biologically equivalent dose (BED) was calculated using the linear–quadratic model. The biological parameters were α/β = 10 Gy, and the dose per fraction (DPF) was d = 3–20 Gy/fr. The isocenter was offset at intervals of 1 mm; 95% of the clinical target volume covered more than 90% of the prescribed physical dose, and BED was defined as biological and physical DMs. The BCF formula was defined as a function of the DPF.ResultsThe difference in the BCF caused by the DPF was within 0.05 for the homogeneous and nonhomogeneous phantoms. In the virtual nonhomogeneous phantom, the data with a PTV margin of 10–20 mm were not significantly different; thus, these were combined to fit the BCF. In the virtual homogeneous phantom, the BCF was fitted to each PTV margin.ConclusionsThe current study improved a scheme to estimate the BDM considering the size of the PTV margin and homogeneous and nonhomogeneous regions. This technique is expected to enable BED-based treatment planning using treatment systems based on physical doses for SBRT.     

An investigation of dose calculation accuracy in intensity-modulated radiotherapy of sites in the head & neck

Knowledge of the accuracy of dose calculations in intensity-modulated radiotherapy of the head and neck is essential for clinical confidence in these highly conformal treatments. High dose gradients are frequently placed very close to critical structures, such as the spinal cord, and good coverage of complex shaped nodal target volumes is important for long term-local control.A phantom study is presented comparing the performance of standard clinical pencil-beam and collapsed-cone dose algorithms to Monte Carlo calculation and three-dimensional gel dosimetry measurement. Calculations and measurements are individually normalized to the median dose in the primary planning target volume, making this a purely relative study. The phantom simulates tissue, air and bone for a typical neck section and is treated using an inverse-planned 5-field IMRT treatment, similar in character to clinically used class solutions.Results indicate that the pencil-beam algorithm fails to correctly model the relative dose distribution surrounding the air cavity, leading to an cverestimate of the target coverage. The collapsed-cone and Monte Carlo results are very similar, indicating that the clinical collapsed-cone algorithm is perfectly sufficient for routine clinical use. The gel measurement shows generally good agreement with the collapsed-cone and Monte Carlo calculated dose, particularly in the spinal cord dose and nodal target coverage, thus giving greater confidence in the use of this class solution.     

Small-animal X-ray dose from micro-CT

The use of micro-CT in small animals has increased in recent years. Although the radiation levels used for micro-CT are generally not lethal to the animal, they are high enough where changes in the immune response and other biological pathways may alter the experimental outcomes. Therefore, it is important to understand what the doses are for a specific imaging procedure. Monte Carlo simulation was used to evaluate the radiation dose to small animals (5-40 mm in diameter) as a result of X-ray exposure. Both monoenergetic (6-100 keV) and polyenergetic (15-100 kVp) X-ray sources were simulated under typical mouse imaging geometries. X-ray spectral measurements were performed on a mouse imaging X-ray system using a commercially available X-ray spectrometer, and spectra from high-energy systems were used as well. For a typical X-ray system with 1.0 mm of added Al at 40 kVp, the dose coefficients (dose to mouse per air kerma at isocenter) were 0.80, 0.63, 0.52, and 0.44 mGy/mGy for mouse diameters of 10, 20, 30, and 40 mm, respectively. A number of tables and figures are provided for dose estimation over a range of mouse imaging geometries.     

Evaluation of target volume and dose accuracy in intrafractional cases of lung cancer based on 4D-CT and 4D-CBCT images using an in-house dynamic thorax phantom

BackgroundThis study aimed to evaluate the target volume and dose accuracy in intrafraction cases using 4-dimensional imaging modalities and an in-house dynamic thorax phantom. Intrafraction motion can create errors in the definition of target volumes, which can significantly affect the accuracy of radiation delivery. Motion management using 4-dimensional modalities is required to reduce the risk.Materials and methodsTwo variations in both breathing amplitude and target size were applied in this study. From these variations, internal target volume (ITVs) contoured in 10 phases of 4D-CT (ITV₁₀), average intensity projection (AIP), and mid-ventilation (Mid-V) images were reconstructed from all 4D-CT datasets as reference images. Free-breathing (FB), augmentation free-breathing (Aug-FB), and static images were also acquired using the 3D-CT protocol for comparisons. In dose evaluations, the 4D-CBCT modality was applied before irradiation to obtain position correction. Then, the dose was evaluated with Gafchromic film EBT3.ResultsThe ITV₁₀, AIP, and Mid-V provide GTVs that match the static GTV. The AIP and Mid-V reference images allowed reductions in ITVs and PTVs without reducing the range of target movement areas compared to FB and Aug-FB images with varying percentages in the range of 29.17% to 48.70%. In the dose evaluation, the largest discrepancies between the measured and planned doses were 10.39% for the FB images and 9.21% for the Aug-FB images.ConclusionThe 4D-CT modality can enable accurate definition of the target volume and reduce the PTV. Furthermore, 4D-CBCT provides localization images during registration to facilitate position correction and accurate dose delivery.