Search PubMed⌕ Search

Biomedical subjects

A E Nahum

Publications and source records attributed to A E Nahum.

At least 19 recordsLinked to original sources
PubMed2002

Optimization of accelerator target and detector for portal imaging using Monte Carlo simulation and experiment.

Megavoltage portal images suffer from poor quality compared to those produced with kilovoltage x-rays. Several authors have shown that the image quality can be improved by modifying the linear accelerator to generate more low-energy photons. This work addresses the problem of using Monte Carlo simulation and experiment to optimize the beam and detector combination to maximize image quality for a given patient thickness. A simple model of the whole imaging chain was developed for investigation of the effect of the target parameters on the quality of the image. The optimum targets (6 mm thick aluminium and 1.6 mm copper) were installed in an Elekta SL25 accelerator. The first beam will be referred to as A16 and the second as Cu1.6. A tissue-equivalent contrast phantom was imaged with the 6 MV standard photon beam and the experimental beams with standard radiotherapy and mammography film/screen systems. The arrangement with a thin Al target/mammography system improved the contrast from 1.4 cm bone in 5 cm water to 19% compared with 2% for the standard arrangement of a thick, high-Z target/radiotherapy verification system. The linac/phantom/detector system was simulated with the BEAM/EGS4 Monte Carlo code. Contrast calculated from the predicted images was in good agreement with the experiment (to within 2.5%). The use of MC techniques to predict images accurately, taking into account the whole imaging system, is a powerful new method for portal imaging system design optimization.

Bone and Bones↗
PubMed2001

Incorporating biologic measurements (SF(2), CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy.

PURPOSE: To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF(2)) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance. METHODS AND MATERIALS: Measurements of SF(2) and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcp(alpha,rho)). Regression analysis was performed to assess the prognostic power of tcp(alpha,rho) vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF(2) and CFE measurements alone. RESULTS: In a univariate regression analysis of 44 patients, tcp(alpha,rho) was a better prognostic factor for both local control and survival (p < 0.001 and p = 0.049, respectively) than SF(2) alone (p = 0.009 for local control, p = 0.29 for survival) or CFE alone (p = 0.015 for local control, p = 0.38 for survival). In multivariate analysis, tcp(alpha,rho) emerged as the most important prognostic factor for local control (p < 0.001, relative risk of 2.81). After allowing for tcp(alpha,rho), CFE was still a significant independent prognostic factor for local control, whereas SF(2) was not. The sensitivities of tcp(alpha,rho) and SF(2) as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively. CONCLUSIONS: A Poisson tcp model incorporating individual SF(2), CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients.

Carcinoma, Squamous Cell↗
PubMed2001

Radiation response and cure rate of human colon adenocarcinoma spheroids of different size: the significance of hypoxia on tumor control modelling.

PURPOSE: To evaluate the adequacy of a Poisson tumor control probability (tcp) model and the impact of hypoxia on tumor cure. METHODS AND MATERIALS: A human colon adenocarcinoma cell line, WiDr, was grown as multicellular spheroids of different diameters. Measurements were made of cell survival and spheroid cure following 300-kV X-ray external beam irradiation in air and nitrogen. Cell survival data were fitted using a two-compartment and an oxygen diffusion model. Spheroid cure data were fitted using the tcp model. RESULTS: Hypoxia was seen only for spheroids greater than 500 microm in diameter. For small spheroids tcp estimates of radiosensitivity and clonogenic number showed excellent agreement with experimentally derived values. For large spheroids, although tcp estimates of radiosensitivity were comparable with measurements, estimates of the clonogenic number were considerably lower than the experimental count. Reoxygenation of large spheroids before irradiation resulted in the tcp estimates of the number of clonogenic cells agreeing with measured values. CONCLUSIONS: When hypoxia was absent, the tcp model accurately predicted cure from measured radiosensitivity and clonogen number. When hypoxia was present, the number of cells capable of regrowth in situ was considerably lower than the number of clonogenic cells that initially survived irradiation. As this counteracted the decreased radiosensitivity, hypoxia was less important for cure than predicted from cell survival assays. This finding suggests that chronic hypoxia may not limit directly the success of radiation therapy.

Adenocarcinoma↗
PubMed2001

Correlations between dose-surface histograms and the incidence of long-term rectal bleeding following conformal or conventional radiotherapy treatment of prostate cancer.

BACKGROUND AND PURPOSE: In a randomized trial, the incidence of rectal bleeding among patients treated for prostate cancer using conformal radiotherapy was significantly lower (p = 0.002) than that among those treated conventionally. Here the relationship between rectal dose distributions and incidences of bleeding is assessed. METHODS AND MATERIALS: Rectal dose-surface histograms (DSHs) have been calculated for 79 trial patients. The relationship between the DSHs and incidences of Grade 1-3 bleeding has been explored using both semiempiric and biologic (parallel) model-based approaches. RESULTS: Semiempiric analysis of the trial data suggests that it is more useful to work with DSH fractional surface areas multiplied by outlined rectal lengths than with either raw DSH fractional areas or fractional areas multiplied by absolute total outlined rectal surface area. Fitting the parallel model to length-multiplied rectal DSHs and complication data reveals the existence of a significant volume effect, the rate of Grade 1-3 bleeding falling by 1.1% (95% confidence interval [0.04, 2.2]%) for each 1% decrease in the fraction of rectal wall (outlined over an 11-cm length) receiving a dose of more than 57 Gy. CONCLUSION: The existence of this volume effect suggests that dose escalation can be achieved using conformal techniques, although the extent to which doses may be safely escalated cannot be reliably estimated from the trial data.

Algorithms↗
PubMed2001

Individualization of dose prescription based on normal-tissue dose-volume and radiosensitivity data.

PURPOSE: The aim of this paper is to illustrate the potential gain in tumor control probability (TCP) of prostate cancer patients by individualizing the prescription dose according to both normal-tissue (N-T) dose-volume and radiosensitivity data. METHODS AND MATERIALS: Two exercises have been carried out. Firstly, patients' dose prescriptions were individualised on the basis of N-T dose-volume histograms (DVHs) alone and secondly modeling potential differences in N-T sensitivity as well. In both cases, the change in tumor control that may be achieved by individualizing patients' dose was estimated assuming that after the dose adjustments, every patient had (1) the same value of normal tissue complication probability (NTCP) (5%) and (2) NTCP equal to the average NTCP before individualization (i.e., without increasing the average NTCP). The Lyman-Kutcher-Burman NTCP model was used to predict the N-T response curves with two different sets of parameters. The first exercise, based only on individual NT DVHs (i.e., assuming all patient equally radiosensitive), was over a real population of 50 prostate cancer patients. The second exercise modeled a 10,000-prostate-cancer patient population with varying NT dose-volume distributions and radiosensitivity (through allowing TD(50) to vary). RESULTS: A gain of more than 9% in TCP was predicted when doses were individualized based only on DVHs so that every patient had 5% NTCP after dose adjustments. By adding the estimate of radiosensitivity, the gain increased to more than 15%. When the individualisation was performed without increasing the mean NTCP, then the potential gain in TCP was almost 5% (for adjustment based on DVH distribution solely) increasing to 7% with the additional consideration of radiosensitivity. CONCLUSIONS: There is a potential gain (increase in local tumor control) from dose individualisation strategies based on both N-T dose-volume data and radiosensitivity (assuming that this is available). Dose prescription individualization based only on dose-volume data can be exploited provided that reliable N-T response models are available. There will be additional gains if some estimate of N-T radiosensitivity is available to allow further patient stratification, identification of patients with high radiosensitivity being particularly important.

Algorithms↗
PubMed2001

Series model volume effects in a population of non-identical patients: how low is low?

Working with several mechanisms of critical local tissue damage, formulae are analytically derived that describe normal tissue complication probabilities (ntcps) for series-type radiotherapy complications arising in heterogeneous patient populations. Using the formulae, values are calculated for deltaD50(10)-the increase in dose leading to a 50% series-type complication rate (D50) when irradiated organ volume is reduced tenfold. From the structure of the ntcp formulae derived, it follows that dose-levels leading to clinically relevant serious complication rates (less than 5%) will change less with irradiated volume than will D50. Calculated values of deltaD50(10) for the heterogeneous series model are low-generally less than 6 Gy; such values are much lower than those calculated for the non-heterogeneous series model (27-37 Gy). These results suggest that if the dose-limiting toxicity of a radiotherapy treatment is a series-type complication with a local damage mechanism similar to any of those studied in this work, then even very substantial improvements in technique-leading to large reductions in highly dosed normal tissue volumes-would be unlikely to allow a useful degree of escalation of the dose delivered to the tumour, unless highly dosed normal tissue volumes can be reduced below the length-scale of a functional subunit.

Cohort Studies↗
PubMed2001

Impact of dose-distribution uncertainties on rectal ntcp modeling. I: Uncertainty estimates.

A trial of nonescalated conformal versus conventional radiotherapy treatment of prostate cancer has been carried out at the Royal Marsden NHS Trust (RMH) and Institute of Cancer Research (ICR), demonstrating a significant reduction in the rate of rectal bleeding reported for patients treated using the conformal technique. The relationship between planned rectal dose-distributions and incidences of bleeding has been analyzed, showing that the rate of bleeding falls significantly as the extent of the rectal wall receiving a planned dose-level of more than 57 Gy is reduced. Dose-distributions delivered to the rectal wall over the course of radiotherapy treatment inevitably differ from planned distributions, due to sources of uncertainty such as patient setup error, rectal wall movement and variation in the absolute rectal wall surface area. In this paper estimates of the differences between planned and treated rectal dose-distribution parameters are obtained for the RMH/ICR nonescalated conformal technique, working from a distribution of setup errors observed during the RMH/ICR trial, movement data supplied by Lebesque and colleagues derived from repeat CT scans, and estimates of rectal circumference variations extracted from the literature. Setup errors and wall movement are found to cause only limited systematic differences between mean treated and planned rectal dose-distribution parameter values, but introduce considerable uncertainties into the treated values of some dose-distribution parameters: setup errors lead to 22% and 9% relative uncertainties in the highly dosed fraction of the rectal wall and the wall average dose, respectively, with wall movement leading to 21% and 9% relative uncertainties. Estimates obtained from the literature of the uncertainty in the absolute surface area of the distensible rectal wall are of the order of 13%-18%. In a subsequent paper the impact of these uncertainties on analyses of the relationship between incidences of bleeding and planned rectal dose-distributions is explored.

Dose-Response Relationship, Radiation↗
PubMed2001

Monte Carlo calculation of output factors for circular, rectangular, and square fields of electron accelerators (6-20 MeV).

Monte Carlo (MC) techniques can be used to build a simulation model of an electron accelerator to calculate output factors for electron fields. This can be useful during commissioning of electron beams from a linac and in clinical practice where irregular fields are also encountered. The Monte Carlo code BEAM/EGS4 was used to model electron beams (6-20 MeV) from a Varian 2100C linear accelerator. After optimization of the Monte Carlo simulation model, agreement within 1% to 2% was obtained between calculated and measured (with a Si diode) lateral and depth dose distributions or within 1 mm in the penumbral regions. Output factors for square, rectangular, and circular fields were measured using two different plane-parallel ion chambers (Markus and NACP) and compared to MC simulations. The agreement was usually within 1% to 2%. This study was not primarily concerned with minimizing the simulation time required to obtain output factors but some considerations with respect to this are presented. It would be particularly useful if the MC model could also be used to calculate output factors for other, similar linacs. To see if this was possible, the primary electron energies in the MC model were retuned to model a recently commissioned similar linac. Good agreement between calculated and measured output factors was obtained for most field sizes for this second accelerator.

Biophysical Phenomena↗
PubMed2000

BIOPLAN: software for the biological evaluation of. Radiotherapy treatment plans.

Distributions of absorbed dose do not provide information on the biological response of tissues (either tumor or organs at risk [OAR]) to irradiation. BIOPLAN (BiOlogical evaluation of PLANs) has been conceived and developed as a PC-based user-friendly software that allows the user to evaluate a treatment plan from the (more objective) point of view of the biological response of the irradiated tissues, and at the same time, provides flexibility in the use of models and parameters. It requires information on dose-volume histograms (DVHs) and can accept a number of different formats (including DVH files from commercial treatment planning systems). BIOPLAN provides a variety of tools, such as tumor control probability (TCP) calculations (using the Poisson model), normal tissue complication probability (NTCP) calculations (using either the Lyman-Kutcher-Burman or the relative seriality models), the ATCP method, DVH subtraction, plots of NTCP/TCP as a function of prescription dose, tumor and OAR dose statistics, equivalent uniform dose (EUD), individualized dose prescription, and parametric sensitivity analysis of the TCP/NTCP models employed.

Humans↗
PubMed2000

Monte Carlo dose calculations and radiobiological modelling: analysis of the effect of the statistical noise of the dose distribution on the probability of tumour control.

The aim of this work is to investigate the influence of the statistical fluctuations of Monte Carlo (MC) dose distributions on the dose volume histograms (DVHs) and radiobiological models, in particular the Poisson model for tumour control probability (tcp). The MC matrix is characterized by a mean dose in each scoring voxel, d, and a statistical error on the mean dose, sigma(d); whilst the quantities d and sigma(d) depend on many statistical and physical parameters, here we consider only their dependence on the phantom voxel size and the number of histories from the radiation source. Dose distributions from high-energy photon beams have been analysed. It has been found that the DVH broadens when increasing the statistical noise of the dose distribution, and the tcp calculation systematically underestimates the real tumour control value, defined here as the value of tumour control when the statistical error of the dose distribution tends to zero. When increasing the number of energy deposition events, either by increasing the voxel dimensions or increasing the number of histories from the source, the DVH broadening decreases and tcp converges to the 'correct' value. It is shown that the underestimation of the tcp due to the noise in the dose distribution depends on the degree of heterogeneity of the radiobiological parameters over the population; in particular this error decreases with increasing the biological heterogeneity, whereas it becomes significant in the hypothesis of a radiosensitivity assay for single patients, or for subgroups of patients. It has been found, for example, that when the voxel dimension is changed from a cube with sides of 0.5 cm to a cube with sides of 0.25 cm (with a fixed number of histories of 10(8) from the source), the systematic error in the tcp calculation is about 75% in the homogeneous hypothesis, and it decreases to a minimum value of about 15% in a case of high radiobiological heterogeneity. The possibility of using the error on the tcp to decide how many histories to run for a given voxel size is also discussed.

Computer Simulation↗
PubMed2000

Backscatter towards the monitor ion chamber in high-energy photon and electron beams: charge integration versus Monte Carlo simulation.

In some linear accelerators, the charge collected by the monitor ion chamber is partly caused by backscattered particles from accelerator components downstream from the chamber. This influences the output of the accelerator and also has to be taken into account when output factors are derived from Monte Carlo simulations. In this work, the contribution of backscattered particles to the monitor ion chamber response of a Varian 2100C linac was determined for photon beams (6, 10 MV) and for electron beams (6, 12, 20 MeV). The experimental procedure consisted of charge integration from the target in a photon beam or from the monitor ion chamber in electron beams. The Monte Carlo code EGS4/BEAM was used to study the contribution of backscattered particles to the dose deposited in the monitor ion chamber. Both measurements and simulations showed a linear increase in backscatter fraction with decreasing field size for photon and electron beams. For 6 MV and 10 MV photon beams, a 2-3% increase in backscatter was obtained for a 0.5 x 0.5 cm2 field compared to a 40 x 40 cm2 field. The results for the 6 MV beam were slightly higher than for the 10 MV beam. For electron beams (6, 12, 20 MeV), an increase of similar magnitude was obtained from measurements and simulations for 6 MeV electrons. For higher energy electron beams a smaller increase in backscatter fraction was found. The problem is of less importance for electron beams since large variations of field size for a single electron energy usually do not occur.

Electrons↗
PubMed2000

Electron fluence perturbation correction factors for solid state detectors irradiated in megavoltage electron beams.

The perturbation correction factor gamma(p) is defined as the deviation of the absorbed dose in the medium from that predicted by the Spencer-Attix extension of the Bragg-Gray cavity theory where the medium occupies exactly the same volume as the solid state cavity and the electron fluence energy spectrum in the cavity is identical in shape, but not necessarily in magnitude, to that in the medium. The value of gamma(p) has been examined for TL detectors irradiated in megavoltage electron beams (5-20 MeV) using the EGS4 Monte Carlo code. LiF and CaF2 solid state detectors simulated were standard size discs of thickness 1 mm and diameter 3.61 mm irradiated in a water phantom with their centres at d(max) or close to it. Values of gamma(p) for LiF ranged from 0.998 +/- 0.005 to 0.994 +/- 0.005 for electron beams with initial energies of 5 and 20 MeV respectively. For CaF2 the corresponding values were 0.956 +/- 0.006 to 0.989 +/- 0.006 for the same size cavities irradiated at the same depth. EGS4 Monte Carlo simulations demonstrate that the total electron fluence (primary electrons and delta-rays) in these solid state detector materials is significantly different from that in water for the same incident electron energy and depth of irradiation. Thus the Spencer-Attix assumption that the electron fluence energy spectrum in the cavity is identical in shape to that in the medium is violated. Differences in the total electron fluence give rise to electron fluence perturbation correction factors which were up to 5% less than unity for CaF2, indicating a strong violation in this case, but were generally less than 1% for LiF. It is the density of the cavity which perturbs the electron fluence, but it is actually the atomic number differences between the medium and cavity that are responsible for the large electron fluence perturbation correction factors for detectors irradiated close to d(max) because the atomic number affects the change in stopping power with energy. When correction is made for the difference between the electron fluence spectrum in the uniform water phantom and the solid state cavity, the Spencer-Attix cavity equation predicts the dose to water within 0.3% in both clinical and monoenergetic electron beams. Harder's formulation for computing the average mass collision stopping power of water to calcium fluoride, surprisingly, requires perturbation correction factors that are closer to unity than those determined using the Spencer-Attix integrals at depths close to d(max).

Electrons↗
PubMed2000

Photon fluence perturbation correction factors for solid state detectors irradiated in kilovoltage photon beams.

Dose perturbation correction factors, gamma(p), for LiF, CaF2 and Li2B4O7 solid state detectors have been determined using the EGS4 Monte Carlo code. Each detector was simulated in the form of a disc of diameter 3.61 mm and thickness 1 mm irradiated in a clinical kilovoltage photon beam at a depth of 1 cm in a water phantom. The perturbation correction factor gamma(p) is defined as the deviation of the absorbed dose ratio from the average mass energy absorption coefficient ratio of water to the detector material, (mu(en)/rho)med,det, which is evaluated assuming that the photon fluence spectrum in the medium and in the detector material are identical. We define another mass energy absorption coefficient ratio, (kappa(en)/rho)med,det, which is evaluated using the actual photon fluence spectrum in the medium and detector for LiF and CaF2 rather than assuming they are identical. (kappa(en)/rho)med,det predicts the average absorbed dose ratio of the medium to the detector material within 0.3%. When the difference in atomic number between the cavity and the phantom material is large then their photon fluence spectra will differ substantially resulting in a difference between (kappa(en)/rho)med,det and (mu(en)/rho)med,det. The value of gamma(p) calculated using (mu(en)/rho)med,det is up to 27% greater than unity for a cavity of CaF2 in 50 kV x-rays. When the atomic number of the medium and detector are similar, their photon fluence spectra are similar, and the difference between (kappa(en)/rho)med,det and (mu(en)/rho)med,det is small. For instance their difference for LiF is less than 2%. The average mass energy absorption coefficient ratio, (mu(en)(E)/rho)w,LiF, evaluated using the mean or representative energy, E, is up to 8% different from (mu(en)/rho)w,LiF. For calcium fluoride the difference between (mu(en)/rho)w,CaF2 and (mu(en)(E)/rho)w,CaF2 is up to 42% in the energy range studied.

Models, Theoretical↗
PubMed2000

Converting absorbed dose to medium to absorbed dose to water for Monte Carlo based photon beam dose calculations.

Current clinical experience in radiation therapy is based upon dose computations that report the absorbed dose to water, even though the patient is not made of water but of many different types of tissue. While Monte Carlo dose calculation algorithms have the potential for higher dose accuracy, they usually transport particles in and compute the absorbed dose to the patient media such as soft tissue, lung or bone. Therefore, for dose calculation algorithm comparisons, or to report dose to water or tissue contained within a bone matrix for example, a method to convert dose to the medium to dose to water is required. This conversion has been developed here by applying Bragg-Gray cavity theory. The dose ratio for 6 and 18 MV photon beams was determined by computing the average stopping power ratio for the primary electron spectrum in the transport media. For soft tissue, the difference between dose to medium and dose to water is approximately 1.0%, while for cortical bone the dose difference exceeds 10%. The variation in the dose ratio as a function of depth and position in the field indicates that for photon beams a single correction factor can be used for each particular material throughout the field for a given photon beam energy. The only exception to this would be for the clinically non-relevant dose to air. Pre-computed energy spectra for 60Co to 24 MV are used to compute the dose ratios for these photon beams and to determine an effective energy for evaluation of the dose ratio.

Air↗
PubMed2000

Effects of cellular repair and proliferation on targeted radionuclide therapy: a modelling study.

A previous targeted radionuclide therapy modelling study has been extended to include the radiobiological effects of cellular repair and proliferation. Dose distributions have been converted into biologically effective dose (BED) distributions using a previously published formulation. With suitable estimated parameters, corrected tumour control probability (TCP) values were derived. The dependence of BED on the physical half-life of the radionuclide was also modelled. Results indicate that the TCP is greater when a shorter physical half-life is employed.

Cell Division↗
PubMed2000

An analysis of the relationship between radiosensitivity and volume effects in tumor control probability modeling.

The dependence of local tumor control probability (tcp) on tumor volume is analyzed and discussed with the help of radiobiological modeling; in particular the impact of possible correlations between mean tumor radiosensitivity and tumor dimensions on the tcp volume dependence is explored. The linear-quadratic Poissonian tumor control probability (tcp) model was modified to account for the possible dependence of clonogenic cell density and radiosensitivity parameters on tumor volume; then the original and modified versions of the model were fitted to published clinical and laboratory tumor control data. These different versions of the tcp model often fitted tumor control data equally well, because of the high degree of correlation between the parameters. Nevertheless the results were very different from a physical point of view and we suggest that sometimes it is possible to choose between equally good fits on the basis of physical considerations. Possible links between the volume dependence of the mean radiosensitivity and the degree of tumor hypoxia were also analyzed through a comparison of the results of the tcp fit to published measurements of oxygen tension in tumors.

Animals↗
PubMed1999

The delta-TCP concept: a clinically useful measure of tumor control probability.

PURPOSE: The aim of this article is to provide a quantitative tool to evaluate the influence of the different dose regions in a non-uniformly irradiated tumour upon the probability of controlling that tumor. METHODS AND MATERIALS: First, a method to generate a distribution of the probability of controlling the cells in a voxel (VCP) is explored and found not to be useful. Second, we introduce the concept of delta-TCP, which represents the gain or loss in the overall TCP as a result of each particular bin in a DVH not receiving the prescribed dose (the same concept is applicable to dose cubes or to a fraction of the bin). The delta-TCP method presented here is based on the Poisson TCP model, but any other model could also be used. Third, using this tool, with parameters appropriate to Stage C prostate tumors, the consequences of "cold" and "hot" dose regions have been explored. RESULTS: We show that TCP is affected by the minimum dose, even if it is delivered to a very small volume (20% dose deficit to 5% of the volume makes the TCP decrease by 18%), and that a hot region may be "wasted" unless the boost is to the bulk of the volume. An example of the application of the delta-TCP concept to a prostate radiotherapy plan is also given. CONCLUSION: The delta-TCP distribution adds more objective information to the original DVH by enabling the clinician or planner to directly evaluate the effects of a non-uniform dose distribution on local control.

Algorithms↗