An on-lattice agent-based Monte Carlo model simulating the growth kinetics of multicellular tumor spheroids.

PURPOSE: To develop an on-lattice agent-based model describing the growth of multicellular tumor spheroids using simple Monte Carlo tools. METHODS: Cells are situated on the vertices of a cubic grid. Different cell states (proliferative, hypoxic or dead) and cell evolution rules, driven by 10 parameters, and the effects of the culture medium are included. About twenty spheroids of MCF-7 human breast cancer were cultivated and the experimental data were used for tuning the model parameters. RESULTS: Simulated spheroids showed adequate sizes of the necrotic nuclei and of the hypoxic and proliferative cell phases as a function of the growth time, mimicking the overall characteristics of the experimental spheroids. The relation between the radii of the necrotic nucleus and the whole spheroid obtained in the simulations was similar to the experimental one and the number of cells, as a function of the spheroid volume, was well reproduced. The statistical variability of the Monte Carlo model described the whole volume range observed for the experimental spheroids. Assuming that the model parameters vary within Gaussian distributions it was obtained a sample of spheroids that reproduced much better the experimental findings. CONCLUSIONS: The model developed allows describing the growth of in vitro multicellular spheroids and the experimental variability can be well reproduced. Its flexibility permits to vary both the agents involved and the rules that govern the spheroid growth. More general situations, such as, e. g., tumor vascularization, radiotherapy effects on solid tumors, or the validity of the tumor growth mathematical models can be studied.

Air density dependence of the response of the PTW SourceCheck 4pi ionization chamber for 125I brachytherapy seeds.

PURPOSE: To analyze the air density dependence of the response of the new SourceCheck 4pi ionization chamber, manufactured by PTW. METHODS: The air density dependence of three different SourceCheck 4pi chambers was studied by measuring 125I sources. Measurements were taken by varying the pressure from 746.6 to 986.6hPa in a pressure chamber. Three different HDR 1000 Plus ionization chambers were also analyzed under similar conditions. A linear and a potential-like function of the air density were fitted to experimental data and their achievement in describing them was analyzed. RESULTS: SourceCheck 4pi chamber response showed a residual dependence on the air density once the standard pressure and temperature factor was applied. The chamber response was overestimated when the air density was below that under normal atmospheric conditions. A similar dependence was found for the HDR 1000 Plus chambers analyzed. A linear function of the air density permitted a very good description of this residual dependence, better than with a potential function. No significant variability between the different specimens of the same chamber model studied was found. CONCLUSION: The effect of overestimation observed in the chamber responses once they are corrected for the standard pressure and temperature may represent a non-negligible ∼4% overestimation in high altitude cities as ours (700m AMSL). This overestimation behaves linearly with the air density in all cases analyzed.

Management of interruptions to fractionated radiotherapy treatments: Four and a half years of experience.

BACKGROUND AND PURPOSE: The study objective was to report our four-and-a half years experience (March 1 2011-August 15 2015) of a program to manage interruptions in fractionated radiotherapy treatments. METHODS: A program was developed, based on a specific database, to manage treatment interruptions. Benefits of the program were analyzed in reference to previously published data. Analysis was also performed of two measures to reduce OTT prolongation and improve treatment outcomes: working on public holidays and conducting treatment unit maintenance on Saturdays. RESULTS: The study included 2352 patients. Patients with head and neck cancer obtained the greatest benefit from the program, with a mean increase in TCP of 3.5% and a benefit of at least 4% in 45.6% of them. In prostate cancer patients, the likelihood of biochemical failure was reduced by a mean of 2.0% and was reduced by at least 4% in 19.7% of them. Application of the two proposed measures would have improved the TCP by a mean of 5.4% in head and neck cancer patients. The impact of the compensations program and proposed measures is lesser in the remaining cancer types studied. CONCLUSIONS: Implementation of a compensation program has a significant impact on patients with head and neck or prostate cancer but OTT prolongation remains excessive in many treatments. The introduction of fractions on public holidays would assist in the meeting of recommendations for these patients.

A method to relate StarTrack(®) measurements to R50 variations in clinical linacs.

The relation between the data recorded with any device for the daily checking of the behavior of a clinical linac and the reference magnitudes to be monitored may be unknown. An experimental method relating the energy stability of the electron beam measured with StarTrack(®) to the R50 beam quality index is proposed. The bending magnet current is varied producing a change in the exit energy window and, therefore, a modification of the R50 value. For different values of this current, the output data of StarTrack(®) and the R50, obtained from depth doses measured in a water phantom are determined. A linear fit between both sets of data allows the identification of the StarTrack(®) output that provides the best way to obtain the quality index R50, for each beam nominal energy. Using these fits, an historical datum series is used to analyze the method proposed in the daily quality control. The ouput data of the StarTrack(®) and the R50 values show a good linear correlation. It is possible to establish a methodology that allows the monitoring of R50 by direct use of the daily quality control data measured with StarTrack(®). A method to monitor R50 in the daily quality control using the StarTrack(®) device has been developed. The method may be applied to similar devices in which the statistical control variable does not show a linear behavior with R50.

Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids.

OBJECTIVE: We propose and study a new model aimed at describing the low-dose hyper-radiosensitivity phenomenon appearing in the survival curves of different cell lines. METHODS: The model uses the induced repair assumption, considering that the critical dose at which this mechanism begins to act varies from cell to cell in a given population. The model proposed is compared with the linear-quadratic model and the modified linear-quadratic model, which is commonly used in literature and in which the induced repair is taken into account in a heuristic way. The survival curve for the MCF-7 line of human breast cancer is measured at low absorbed doses and the uncertainties in these doses are estimated using thermoluminiscent dosemeters. RESULTS: It is shown that these multicellular spheroids present low-dose hyper-radiosensitivity. The new model permits an accurate description of the data of two human cell lines (previously published) and of the multicellular spheroids of the MCF-7 line here measured. CONCLUSION: The model shows enough flexibility to account for data with very different characteristics and considers in a faithful way the hypothesis of the repair induction.

Quality control for system count rate performance with scatter in gamma cameras.

We aimed to analyze the optimal conditions to carry out the periodical statistical control tests of the gamma camera count rate performance. First we focused in reproducing the actual R(20) value of the gamma camera response. Second we studied the variability of this parameter in the statistical control test. We performed a reference measurement, which consisted of the determination of the complete curve relating observed and incident count rates, the counting model describing it and the reference R(20). This reference determined the conditions for the statistical control tests and the way to analyze the results obtained. Results from three different gamma cameras were studied. Each gamma camera showed a different behavior and required specific data analysis. The optimal conditions to perform the statistical control test were determined in each case. Our procedure provides the information necessary to correlate the average value of R(20) obtained in the quality control test with the reference one. The critical requirement to perform any statistical control test, that is to have a reduced variability of the control variable, can be fulfilled in this case only for relatively high activities.

A Monte Carlo tool to simulate breast cancer screening programmes.

A Monte Carlo tool which permits the simulation of screening mammography programmes is developed. Various statistical distributions describing different parameters involved in the problem are used: the characteristics of the population under study, a tumour growth model and a model for tumour detection based on parameters such as sensitivity and specificity which depends on the woman's age. We reproduce results of different actual programmes. The model enables us to find out the configuration (the age of the women who attend the screening trials and screening frequency) which produces maximum benefits with minimum risks. In addition, the model has permitted us to validate some of the assumed hypothesis, such as the probability distribution of the tumour detection as a function of the tumour size, the frequency of the histological types and the transition probability between different histological types.

Monte Carlo simulation using the PENELOPE code with an ant colony algorithm to study MOSFET detectors.

In this work we have developed a simulation tool, based on the PENELOPE code, to study the response of MOSFET devices to irradiation with high-energy photons. The energy deposited in the extremely thin silicon dioxide layer has been calculated. To reduce the statistical uncertainties, an ant colony algorithm has been implemented to drive the application of splitting and Russian roulette as variance reduction techniques. In this way, the uncertainty has been reduced by a factor of approximately 5, while the efficiency is increased by a factor of above 20. As an application, we have studied the dependence of the response of the pMOS transistor 3N163, used as a dosimeter, with the incidence angle of the radiation for three common photons sources used in radiotherapy: a (60)Co Theratron-780 and the 6 and 18 MV beams produced by a Mevatron KDS LINAC. Experimental and simulated results have been obtained for gantry angles of 0 degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees and 75 degrees. The agreement obtained has permitted validation of the simulation tool. We have studied how to reduce the angular dependence of the MOSFET response by using an additional encapsulation made of brass in the case of the two LINAC qualities considered.

Dose dependence of the growth rate of multicellular tumour spheroids after irradiation.

The present study investigated differences in the growth rate of multicellular tumour spheroids of the MCF-7 line of human breast cancer before and after their irradiation. Growth of the spheroids was analysed according to a model based on a Gompertz function. In this model, normalization to a common initial volume is achieved in a way that enables meaningful comparisons to be made between the results obtained for each spheroid. For irradiated spheroids the model includes an additional term to take account of sterilized cells. We found that the growth rate observed before irradiation is not fully recovered by irradiated spheroids and that growth recovery reduces with higher irradiation doses. Surviving fractions obtained at doses below 3 Gy are comparable with those found in clonogenic assays on spheroids of the same cellular line. At larger doses, discrepancies between the different studies are considerable.

Cribado mamográfico. Réplica

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A method to determine the in-air spatial spread of clinical electron beams.

We propose and analyze in detail a method to measure the in-air spatial spread parameter of clinical electron beams. Measurements are performed at the center of the beam and below the adjustable collimators sited in asymmetrical configuration in order to avoid distortions due to the presence of the applicator. The main advantage of our procedure lies in the fact that the dose profiles are fitted by means of a function which includes, in addition to the Gaussian step usually considered, a background which takes care of the dose produced by different mechanisms for which the Gaussian model does not account. As a result, the spatial spread is obtained directly from the fitting procedure and the accuracy permits a good determination of the angular spread. The way the analysis is done is alternative to that followed by the usual methods based on the evaluation of the penumbra width. Besides, the spatial spread found shows quadratic-cubic dependence with the distance to the source predicted by the Fermi-Eyges theory. However, the corresponding values obtained for the scattering power are differing from those quoted by ICRU nr. 35 by a factor of approximately 2 or larger, which requires of a more detailed investigation.