Damián Guirado

Effect on tumour control of time interval between surgery and postoperative radiotherapy: an empirical approach using Monte Carlo simulation

In this work, a procedure, based on Monte Carlo techniques, to analyse the effect on the tumour control probability of the time interval between surgery and postoperative radiotherapy is presented. The approach includes the tumour growth as well as the survival of tumour cells undergoing fractionated radiotherapy. Both processes are described in terms of the binomial distribution. We have considered two different growth models, exponential and Gompertz, the parameters of which have been fixed to reproduce the clinical outcome corresponding to a retrospective study for patients with head and neck squamous cell carcinomas. In the cases analysed, we have not found significant differences between the results obtained for both growth models. The mean doubling times found for residual clonogens after surgery are less than 40 days. The rate of decrease in local control is around 0.09% per day of delay between surgery and radiotherapy and the corresponding time factor is about 0.11 Gy per day.

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 womans 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.

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.

Dependence with air density of the response of the PTW SourceCheck ionization chamber for low energy brachytherapy sources

PURPOSE Air-communicating well ionization chambers are commonly used to assess air kerma strength of sources used in brachytherapy. The signal produced is supposed to be proportional to the air density within the chamber and, therefore, a density-independent air kerma strength is obtained when the measurement is corrected to standard atmospheric conditions using the usual temperature and pressure correction factor. Nevertheless, when assessing low energy sources, the ionization chambers may not fulfill that condition and a residual density dependence still remains after correction. In this work, the authors examined the behavior of the PTW 34051 SourceCheck ionization chamber when measuring the air kerma strength of (125)I seeds. METHODS Four different SourceCheck chambers were analyzed. With each one of them, two series of measurements of the air kerma strength for (125)I selectSeed(TM) brachytherapy sources were performed inside a pressure chamber and varying the pressure in a range from 747 to 1040 hPa (560 to 780 mm Hg). The temperature and relative humidity were kept basically constant. An analogous experiment was performed by taking measurements at different altitudes above sea level. RESULTS Contrary to other well-known ionization chambers, like the HDR1000 PLUS, in which the temperature-pressure correction factor overcorrects the measurements, in the SourceCheck ionization chamber they are undercorrected. At a typical atmospheric situation of 933 hPa (700 mm Hg) and 20 °C, this undercorrection turns out to be 1.5%. Corrected measurements show a residual linear dependence on the density and, as a consequence, an additional density dependent correction must be applied. The slope of this residual linear density dependence is different for each SourceCheck chamber investigated. The results obtained by taking measurements at different altitudes are compatible with those obtained with the pressure chamber. CONCLUSIONS Variations of the altitude and changes in the weather conditions may produce significant density corrections, and that effect should be taken into account. This effect is chamber-dependent, indicating that a specific calibration is necessary for each particular chamber. To our knowledge, this correction has not been considered so far for SourceCheck ionization chambers, but its magnitude cannot be neglected in clinical practice. The atmospheric pressure and temperature at which the chamber was calibrated need to be taken into account, and they should be reported in the calibration certificate. In addition, each institution should analyze the particular response of its SourceCheck ionization chamber and compute the adequate correction factors. In the absence of a suitable pressure chamber, a possibility for this assessment is to take measurements at different altitudes, spanning a wide enough air density range.

Statistical control of the spectral quality index in electron beams.

BACKGROUND AND PURPOSE In radiotherapy with electron linear accelerators, it is mandatory to guarantee the stability of beam output spectra. In this work we study the quality control of the magnitude that provides the beam spectral quality, by following statistical techniques usual in industry process. METHODS We establish the differences between the measurement of the reference quality index, R(50,ion), which involves usually a costly procedure, and that of the index used for the statistical control, which can be done in an easier way and with a higher frequency. The methodology developed is applied to a Siemens Mevatron KDS electron linear accelerator, specifically for the 6, 12 and 18 MeV modes. The uncertainties of both procedures are evaluated and are correlated. A retrospective analysis of the data registered during more than 13 years is carried out using CUSUM algorithmic and moving range charts. RESULTS The larger uncertainties in R(50,ion) come from the measurement device and the observer. The uncertainty in the measurement of the statistical control variable, which is mainly due to the geometry setup, is negligible against its intrinsic variability. The application of CUSUM charts pointed out different out of control situations linked in much cases to assignable causes. In addition, moving range charts showed up situations of anomalous functioning of the LINAC. CONCLUSIONS Algorithmic CUSUM charts permit a nice monitoring of R(50,ion). If the variability is not controlled, by using charts such as the moving range ones, the number of false alarms could increase without a change in the mean value of R(50,ion).

A Monte Carlo tool to study the mortality reduction due to breast screening programs.

PURPOSE To develop a Monte Carlo tool that permits to study the reduction in breast cancer mortality rate due to breast screening programs. METHODS Simulations implement woman histories undergoing a screening program, include a model of survival after local treatment of invasive cancers and use distributions of time gained due to screening detection against symptomatic detection and overall sensitivity of the screening obtained previously. Mortalities for the whole woman population and for those women with ages within the range considered in the program have been calculated. RESULTS For the whole woman population, a reduction in breast cancer mortality up to 29% has been found for a configuration that includes women aged between 50 and 70 years, with a screening interval of two years and 100% acceptance rate. If an acceptance of 70% is considered, this percentage reduces to 20%. If, in the same conditions, the program starts at 40 years, the reduction of the mortality reaches 24% while if the screening interval is one year, this percentage raises to 28%. If mortalities are calculated for those women with ages within the range included in the program these reductions are greater and no significant differences are found between the programs with age ranges [50-70] and [40-70]. In the model, radio-induced cancers have no effect in survival. CONCLUSIONS The results agree reasonably well with those of different trials. Mortality reductions of 12%-20% (between two and four deaths per year and 10(5) women) are obtained only for acceptances above 50%. This could be considered as a threshold for the acceptance, which appears to be a critical parameter.

A Monte Carlo analysis of breast screening randomized trials

PURPOSE To analyze breast screening randomized trials with a Monte Carlo simulation tool. METHODS A simulation tool previously developed to simulate breast screening programmes was adapted for that purpose. The history of women participating in the trials was simulated, including a model for survival after local treatment of invasive cancers. Distributions of time gained due to screening detection against symptomatic detection and the overall screening sensitivity were used as inputs. Several randomized controlled trials were simulated. Except for the age range of women involved, all simulations used the same population characteristics and this permitted to analyze their external validity. The relative risks obtained were compared to those quoted for the trials, whose internal validity was addressed by further investigating the reasons of the disagreements observed. RESULTS The Monte Carlo simulations produce results that are in good agreement with most of the randomized trials analyzed, thus indicating their methodological quality and external validity. A reduction of the breast cancer mortality around 20% appears to be a reasonable value according to the results of the trials that are methodologically correct. Discrepancies observed with Canada I and II trials may be attributed to a low mammography quality and some methodological problems. Kopparberg trial appears to show a low methodological quality. CONCLUSION Monte Carlo simulations are a powerful tool to investigate breast screening controlled randomized trials, helping to establish those whose results are reliable enough to be extrapolated to other populations and to design the trial strategies and, eventually, adapting them during their development.

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.

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 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.