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J O Deasy

Publications and source records attributed to J O Deasy.

17 recordsLinked to original sources

Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose-volume outcome relationships.

Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

Computer Simulation↗

A comparison of Monte Carlo dose calculation denoising techniques.

Recent studies have demonstrated that Monte Carlo (MC) denoising techniques can reduce MC radiotherapy dose computation time significantly by preferentially eliminating statistical fluctuations ('noise') through smoothing. In this study, we compare new and previously published approaches to MC denoising, including 3D wavelet threshold denoising with sub-band adaptive thresholding, content adaptive mean-median-hybrid (CAMH) filtering, locally adaptive Savitzky-Golay curve-fitting (LASG), anisotropic diffusion (AD) and an iterative reduction of noise (IRON) method formulated as an optimization problem. Several challenging phantom and computed-tomography-based MC dose distributions with varying levels of noise formed the test set. Denoising effectiveness was measured in three ways: by improvements in the mean-square-error (MSE) with respect to a reference (low noise) dose distribution; by the maximum difference from the reference distribution and by the 'Van Dyk' pass/fail criteria of either adequate agreement with the reference image in low-gradient regions (within 2% in our case) or, in high-gradient regions, a distance-to-agreement-within-2% of less than 2 mm. Results varied significantly based on the dose test case: greater reductions in MSE were observed for the relatively smoother phantom-based dose distribution (up to a factor of 16 for the LASG algorithm); smaller reductions were seen for an intensity modulated radiation therapy (IMRT) head and neck case (typically, factors of 2-4). Although several algorithms reduced statistical noise for all test geometries, the LASG method had the best MSE reduction for three of the four test geometries, and performed the best for the Van Dyk criteria. However, the wavelet thresholding method performed better for the head and neck IMRT geometry and also decreased the maximum error more effectively than LASG. In almost all cases, the evaluated methods provided acceleration of MC results towards statistically more accurate results.

Algorithms↗

Uncertainties in model-based outcome predictions for treatment planning.

PURPOSE: Model-based treatment-plan-specific outcome predictions (such as normal tissue complication probability [NTCP] or the relative reduction in salivary function) are typically presented without reference to underlying uncertainties. We provide a method to assess the reliability of treatment-plan-specific dose-volume outcome model predictions. METHODS AND MATERIALS: A practical method is proposed for evaluating model prediction based on the original input data together with bootstrap-based estimates of parameter uncertainties. The general framework is applicable to continuous variable predictions (e.g., prediction of long-term salivary function) and dichotomous variable predictions (e.g., tumor control probability [TCP] or NTCP). Using bootstrap resampling, a histogram of the likelihood of alternative parameter values is generated. For a given patient and treatment plan we generate a histogram of alternative model results by computing the model predicted outcome for each parameter set in the bootstrap list. Residual uncertainty ("noise") is accounted for by adding a random component to the computed outcome values. The residual noise distribution is estimated from the original fit between model predictions and patient data. RESULTS: The method is demonstrated using a continuous-endpoint model to predict long-term salivary function for head-and-neck cancer patients. Histograms represent the probabilities for the level of posttreatment salivary function based on the input clinical data, the salivary function model, and the three-dimensional dose distribution. For some patients there is significant uncertainty in the prediction of xerostomia, whereas for other patients the predictions are expected to be more reliable. In contrast, TCP and NTCP endpoints are dichotomous, and parameter uncertainties should be folded directly into the estimated probabilities, thereby improving the accuracy of the estimates. Using bootstrap parameter estimates, competing treatment plans can be ranked based on the probability that one plan is superior to another. Thus, reliability of plan ranking could also be assessed. CONCLUSIONS: A comprehensive framework for incorporating uncertainties into treatment-plan-specific outcome predictions is described. Uncertainty histograms for continuous variable endpoint models provide a straightforward method for visual review of the reliability of outcome predictions for each treatment plan.

Humans↗

A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results.

OBJECTIVES: In a prospective clinical study, we tested the hypothesis that sparing the parotid glands may result in significant objective and subjective improvement of xerostomia in patients with head-and-neck cancers. The functional outcome 6 months after the completion of radiation therapy is presented. METHODS AND MATERIALS: From February 1997 to February 1999, 41 patients with head-and-neck cancers were enrolled in a prospective salivary function study. Inverse-planning intensity-modulated radiation therapy (IMRT) was used to treat 27 patients, and forward-planning three-dimensional radiation therapy in 14. To avoid potential bias in data interpretation, only patients whose submandibular glands received greater than 50 Gy were eligible. Attempts were made to spare the superficial lobe of the parotid glands to avoid underdosing tumor targets in the parapharyngeal space; however, the entire parotid volume was used to compute dose-volume histograms (DVHs) for this analysis. DVHs were computed for each gland separately. Parotid function was assessed objectively by measuring stimulated and unstimulated saliva flow before and 6 months after the completion of radiation therapy. Measurements were converted to flow rate (mL/min) and normalized relative to that before treatment. The corresponding quality-of-life (QOL) outcome was assessed by five questions regarding the patient's oral discomfort and eating/speaking problems. RESULTS: We observed a correlation between parotid mean dose and the fractional reduction of stimulated saliva output at 6 months after the completion of radiation therapy. We further examined whether the functional outcome could be modeled as a function of dose. Two models were found to describe the dose-response data well. The first model assumed that each parotid gland is comprised of multiple independent parallel functional subunits (corresponding to computed tomography voxels) and that each gland contributes equally to overall flow, and that saliva output decreases exponentially as a quadratic function of irradiation dose to each voxel. The second approach uses the equivalent uniform dose (EUD) metrics, which assumes loss of salivary function with increase in EUD for each parotid gland independently. The analysis suggested that the mean dose to each parotid gland is a reasonable indicator for the functional outcome of each gland. The corresponding exponential coefficient was 0.0428/Gy (95% confidence interval: 0.01, 0.09). The QOL questions on eating/speaking function were significantly correlated with stimulated and unstimulated saliva flow at 6 months. In a multivariate analysis, a toxicity score derived from the model based on radiation dose to the parotid gland was found to be the sole significant predictive factor for xerostomia. Neither radiation technique (IMRT vs. non-IMRT) nor chemotherapy (yes or no) independently influenced the functional outcome of the salivary glands. CONCLUSION: Sparing of the parotid glands translates into objective and subjective improvement of both xerostomia and QOL scores in patients with head-and-neck cancers receiving radiation therapy. Modeling results suggest an exponential relationship between saliva flow reduction and mean parotid dose for each gland. We found that the stimulated saliva flow at 6 months after treatment is reduced exponentially, for each gland independently, at a rate of approximately 4% per Gy of mean parotid dose.

Adult↗

Denoising of electron beam Monte Carlo dose distributions using digital filtering techniques.

The Monte Carlo (MC) method has long been viewed as the ultimate dose distribution computational technique. The inherent stochastic dose fluctuations (i.e. noise), however, have several important disadvantages: noise will affect estimates of all the relevant dosimetric and radiobiological indices, and noise will degrade the resulting dose contour visualizations. We suggest the use of a post-processing denoising step to reduce statistical fluctuations and also improve dose contour visualization. We report the results of applying four different two-dimensional digital smoothing filters to two-dimensional dose images. The Integrated Tiger Series MC code was used to generate 10 MeV electron beam dose distributions at various depths in two different phantoms. The observed qualitative effects of filtering include: (a) the suppression of voxel-to voxel (high-frequency) noise and (b) the resulting contour plots are visually more comprehensible. Drawbacks include, in some cases, slight blurring of penumbra near the surface and slight blurring of other very sharp real dosimetric features. Of the four digital filters considered here, one, a filter based on a local least-squares principle, appears to suppress noise with negligible degradation of real dosimetric features. We conclude that denoising of electron beam MC dose distributions is feasible and will yield improved dosimetric reliability and improved visualization of dose distributions.

Algorithms↗

A proton dose calculation algorithm for conformal therapy simulations based on Molière's theory of lateral deflections.

An algorithm is developed for computing proton dose distributions in the therapeutic energy range (100-250 MeV). The goal is to provide accurate pencil beam dose distributions for two-dimensional or three-dimensional simulations of possible intensity-modulated proton therapy delivery schemes. The algorithm is based on Molière's theory of lateral deflections, which accurately describes the distribution of lateral deflections suffered by incident charged particles. The theory is applied to nonuniform targets through the usual pencil beam approximation which assumes that all protons from a given pencil beam pass through the same material at each depth. Fluence-to-dose conversion is made via Monte Carlo calculated broad-field central-axis depth-dose curves, which accounts for attenuation due to nuclear collisions and range straggling. Calculation speed is enhanced by using a best-fit Gaussian approximation of the radial distribution function at depth. Representative pencil beam and spread-out Bragg-peak computations are presented at 250 MeV and 160 MeV in water. Computed lateral full-widths-at-half-maximum's in water, at the Bragg peak, agree with the expected theoretical lateral values to within 1% at 160 MeV and to within 3% at 250 MeV. This algorithm differs from convolution methods in that the effect of the depth of any inhomogeneities in density or atomic composition are accounted for in a rigorous fashion. The algorithm differs from Fermi-Eyges based methods by accounting in a rigorous way for the effect of nonsmall-angle scattering and screening due to atomic electrons. The computational burden is only slightly greater than that expected using the less-rigorous Fermi-Eyges theory.

Algorithms↗

An investigation of tomotherapy beam delivery.

Experimental simulations for tomotherapy beam delivery were performed using a computer-controlled phantom positioner, a cylindrical phantom, and a 6 MV x-ray slit beam. Both continuous helical beam and sequential segmented tomotherapy (SST) beam deliveries were evaluated. Beam junctioning problem due to couch indexing error or field width errors presented severe dose uniformity perturbations for SST, while the problem was minimized for helical beam delivery. Longitudinal breathing motions were experimentally simulated for helical and SST beam delivery. While motions reduced the dose uniformity perturbations for SST, small artifacts in dose uniformity can be introduced for helical beam delivery. With typical breath frequency and magnitude, for a slit beam of 2.0 cm width at 4 rpm, the dose uniformity perturbation was not significant. A running start/stop technique was implemented with helical beam delivery to sharpen the 20%-80% longitudinal dose fall-off from 1.5 to 0.5 cm. The latter was comparable to the corresponding dose penumbra of a conventional 6 MV 10 x 10 cm2 field. All together, helical beam delivery showed advantages over SST for tomotherapy beam delivery under similar delivery conditions.

Biophysical Phenomena↗

Multiple local minima in radiotherapy optimization problems with dose-volume constraints.

The cause of multiple local minima in beam weight optimization problems subject to dose-volume constraints is analyzed. Three objective functions were considered: (a) maximization of tumor control probability (TCP), (b) maximization of the minimum target dose, and (c) minimization of the mean-squared-deviation of the target dose from the prescription dose. It is shown that: (a) TCP models generally result in strongly quasiconvex objective functions; (b) maximization of the minimum target dose results in a strongly quasiconvex objective function; and (c) minimizing the root-mean-square dose deviation results in a convex objective function. Dose-volume constraints are considered such that, for each region at risk (RAR), the volume of tissue whose dose exceeds a certain tolerance dose (DTol) is kept equal to or below a given fractional level (VTol). If all RARs lack a "volume effect" (i.e., VTol = 0 for all RARs) then there is a single local minimum. But if volume effects are present, then the feasible space is possibly nonconvex and therefore possibly leads to multiple local minima. These conclusions hold for all three objective functions. Hence, possible local minima come not from the nonlinear nature of the objective functions considered, but from the "either this volume or that volume but not both" nature of the volume effect. These observations imply that optimization algorithms for dose-volume constraint types of problems should have effective strategies for dealing with multiple local minima.

Algorithms↗

The dose distribution produced by a 32P source for endovascular irradiation.

PURPOSE: Percutaneous transluminal coronary angioplasty (PTCA) is one of the most common therapies for obstructive coronary artery disease. Unfortunately, subsequent restenosis after percutaneous balloon angioplasty occurs in 30-50% of patients and remains one of the major unsolved problems of contemporary cardiology. The study of endovascular irradiation has been greatly stimulated by the discovery that the process of restenosis may be impaired by irradiation. The objective of this study was to examine a custom-made commercial 32P wire and to determine whether the present source presentation is suitable for this application. METHODS AND MATERIALS: Measurements of the dose distribution around a 3 mm long 32P source with an activity of 0.414 GBq (11.2 mCi) were made by using LiF thermoluminescent dosimeters and a scintillation detector. The source had the dimensions of 0.3 mm in diameter and 3 mm in length, and was first encapsulated by a plastic tube and then encapsulated in a specially manufactured Ni-Ti wire with a diameter of 0.4 mm and a length of 2.6 m. The detector size effect is removed from the measurements calculation. Loevinger's equation for the dose distribution around a 32P source was used for the calculations. RESULTS: The dose rate at a radial distance of 1.5 mm was 53 cGy/s per GBq (1.96 cGy/s per mCi) and fell off rapidly perpendicularly to the axis of the source in an approximately exponential manner, from 53-5.3 cGy/s per GBq (approximately 2 to 0.2 cGy/s per mCi) as radial distances increased from 0.2 to 0.4 g/cm2 (1.5 to 3.5 mm away from the center of the source). The treatment length parallel along the wire could be as long as 24 mm for eight source dwell positions with the average dose rate of 59 cGy/s per GBq (2.2 cGy/s per mCi) and a variation of +/- 2.3% at a radial distance of 1.5 mm. CONCLUSIONS: Our experiments show that the dose distribution is ideal for endovascular irradiation. The source was incorporated in the end of a flexible cable and with a half-life of 14.3 days is suitable for endovascular irradiation.

Brachytherapy↗

Measured electron energy and angular distributions from clinical accelerators.

Electron energy spectra and angular distributions, including angular spreads, were measured using magnetic spectrometer techniques, at isocenter, for two clinical linear accelerators: one scanning beam machine, which achieves field flatness by scanning a pencil beam over the desired field at the patient plane, and one scattering foil machine, which disperses the electrons through a graded-thickness scattering foil. All measurements were made at isocenter (in the patient plane), in air, 1 m from the nominal accelerator source. The energy measurements were confined to electrons traveling along the central axis; any widely scattered electrons were effectively neglected. The energy spectra of the scanning beam machine are all of nearly Gaussian shape and energy full-width-at-half-maximum intensity (FWHM) of about 5% of the peak mean energy (denoted (E0)*). The energy spectra of the scattering foil machine have a variety of forms as a function of energy, including even spectra with double peaks, and spectra which changed with time. The FWHM values ranged from 9%-22% of (E0)*. The angular spread measurements, at isocenter, yielded sigma theta (x) x (E0)* approximately 295 mrad-MeV for the scanning beam machine, and 346 mrad-MeV for the scattering foil machine, where sigma theta x denotes the standard deviation of the plane-projected angular distribution. These angular spreads are 30%-40% smaller than angular spreads reported by others on a very similar machine using the penumbra method. Possible causes of this discrepancy are discussed.

Electrons↗

A proof that uniform dose gives the greatest TCP for fixed integral dose in the planning target volume.

In this note it is shown that for a fixed integral dose to the planning target volume, the highest tumour control probability (TCP) arises when the dose is spatially uniform. This 'uniform dose theorem' is proved both for (i) a specific TCP model based on Poisson/independent voxel statistics, and (ii) any model for voxel control probability having a specific shape with respect to increasing dose.

Dose-Response Relationship, Radiation↗

The spectral dependence of electron central-axis depth-dose curves.

Electron linac fields are usually characterized by the central-axis practical range in water, Rp, and the depth of half maximum dose, R50, for dosimetry, quality assurance, and treatment planning. The quantitative relations between the range parameters and the intrinsic linac beam's energy structure are critically reviewed. The spectral quantity * is introduced which is defined as the mean energy of the incident spectral peak, termed the "peak mean energy." An analytical model is constructed to demonstrate the predicted relation between polyenergetic spectral shapes and the resulting depth-dose curves. The model shows that, in the absence of electrons at the patient plane with energies outside about * +/- 0.1 *, Rp and R50 are both determined by *. This analytical approximation is confirmed by a Monte Carlo calculation comparing two different idealized incident spectra. The effect of contaminant lower energy or wide-angle scattered electrons is also discussed. The effect of the width of the intrinsic energy spread on the shape of the depth-dose curve is investigated using Monte Carlo depth-dose simulations based on measured linac energy spectra having energy spreads (full width at half maximum) as large as 20%. These simulations show that the energy spread has only a small effect on the shape of the central-axis depth-dose curve.

Electrons↗

Extrapolation chamber measurements of 90Sr + 90Y beta-particle ophthalmic applicator dose rates.

Aspects of extrapolation chamber dose-rate measurements of 90Sr + 90Y beta-particle ophthalmic applicators are examined in this report, including the proper choice of collector electrode size, the gap width over which the measurement should be done, the effect of the entrance window materials, and the stopping-power ratio. Experiments, a simple analytic model for the effect of chamber geometry and nonzero gap width, and more detailed Monte Carlo simulations were used. The variation of the planar flux density as a function of angle for a thick 90Sr + 90Y source was measured and used as input for the model. From Monte Carlo simulation, the dose rate for tissue irradiation falls off by 8% between the surface and a depth of 7 mg/cm2. The derivative of chamber ionization as a function of gap width, needed for the dose-rate calibration, increases rapidly as the gap width decreases, typically by a factor of about 2 between gap widths of 1.5 and 0.15 mm. About half of this change is due to ionizing electrons leaving the collection volume at the larger gap widths as shown by the analytic model; the rest of the change is due to ionizing electrons which backscatter from the collector electrode and its backing as shown by Monte Carlo simulations. The backscattering effect increases the derived surface dose by a factor of 1.46. A satisfactory dose-rate extrapolation is obtained from gap widths of 0.1-0.25 mm, where the total ionization current is observed to be nearly linear in gap width.

Beta Particles↗

A simple magnetic spectrometer for radiotherapy electron beams.

A small, lightweight, single-focusing magnetic spectrometer was designed, assembled, and tested for analysis of electron beams from radiotherapy electron linacs. The objective was to develop a low cost, simple device that could be easily replicated in other medical centers, and to demonstrate the practicality of individual electron counting for precise analysis of electron spectra. Two methods of spectroscopy have been developed. One method consists of counting electrons individually as a function of magnetic field setting. Electrons are deflected through 90 degrees in the magnetic spectrometer, through an exit slit, and into a scintillation detector. A second method consists of recording the complete spectrum of electron energies from the accelerator on a strip of film at a single magnetic field setting. A critical design element is the 10-cm long collimator for electrons entering the magnet gap, with defining apertures and scraper slits. The spectrometer's cleanliness of transmission, energy calibration, and resolution were all tested at 10 and 16 MeV using the nearly monoenergetic electron beam of the accelerator at the National Research Council of Canada (NRCC). These accelerator tests, and also Monte Carlo trajectory simulations, both show that contamination of the transmitted spectrum due to scattered or knock-on electrons is negligible. Low-energy characteristics were tested using a 90Sr + 90Y beta-particle source. The energy calibration of the 90 degree spectrometer mode was based on mapping the magnetic field and also electron trajectory computer simulations. That calibration agrees with the NRCC's own calibrated scale to 0.8% for the single-particle counting method and to 1.3% for the film method. The energy resolution was measured to be 2% at 10 MeV, which is adequate for radiotherapy linac measurements. The acceptance half angle is 0.5 degrees or less, depending on the aperture size, which is adequate for electron angular distribution measurements within the forward cone of the electron beam. Used with film, the spectrometer is a simple, accurate, and highly transportable device for measuring radiotherapy electron energy spectra.

Biophysical Phenomena↗

Tomotherapy: a new concept for the delivery of dynamic conformal radiotherapy.

Tomotherapy, literally "slice therapy," is a proposal for the delivery of radiation therapy with intensity-modulated strips of radiation. The proposed method employs a linear accelerator, or another radiation-emitting device, which would be mounted on a ring gantry like a CT scanner. The patient would move through the bore of the gantry simultaneously with gantry rotation. The intensity modulation would be performed by temporally modulated multiple independent leaves that open and close across the slit opening. At any given time, any leaf would be (1) closed, covering a portion of the slit, (2) open, allowing radiation through, or (3) changing between these states. This method would result in the delivery of highly conformal radiation. Overall treatment times should be comparable with contemporary treatment delivery times. The ring gantry would make it convenient to mount a narrow multisegmented megavoltage detector system for beam verification and a CT scanner on the treatment unit. Such a treatment unit could become a powerful tool for treatment planning, conformal treatment, and verification using tomographic images. The physical properties of this treatment delivery are evaluated and the fundamental design specifications are justified.

Humans↗