Marcello Benassi

Monte Carlo dose voxel kernel calculations of beta-emitting and Auger-emitting radionuclides for internal dosimetry: A comparison between EGSnrcMP and EGS4

Dose-point kernels (DPKs) can be widely applied to therapeutic nuclear medicine to obtain more accurate absorbed dose assessments in internal dosimetry assuming a spherical geometry. Recently, EGSnrc-the latest in the family of EGS Monte Carlo codes--has been tested for isotropic monoenergetic electrons and Y-90 beta spectrum in spherical geometry. The availability of SPECT images allows one to take into account heterogeneities in activity distribution within tumors, and to perform dose calculations using voxel dosimetry based on Monte Carlo simulations in a Cartesian geometry. The purpose of this study is to evaluate the differences of dose distributions scored in Cartesian voxels also known as Dose Voxel Kernels (DVKs) for five beta-emitting (131I, 89Sr, 153Sm, 186Re, and 90Y) and Auger-emitting (111In) radionuclides, when their computation is made using these two Monte Carlo codes from the same family to check if the new physics in EGSnrc simulation system produces DVK very different from those calculated with EGS4. We have calculated the DVKs for point and voxel sources in Cartesian scoring grids of different spatial resolutions. Our results for the point source, scored in the finer spatial resolution, show a poor agreement between EGSnrc and EGS4 (up to about 20%) for voxels closer to the origin, and a better agreement (below 5%) for longer distances for all radionuclides. For the voxel source, where doses were scored in the coarser spatial resolution, dose deposition in the central voxel is in good agreement for all the radionuclides; while surrounding voxels exhibit a slightly worse agreement.

A heterogeneous dose distribution in simultaneous integrated boost: the role of the clonogenic cell density on the tumor control probability

IMRT with inverse planning allows simultaneous integrated boost strategies that exploit the heterogeneous dose distribution within the planning target volumes (PTVs). In this scenario, the location of cold spots within the target becomes a crucial issue and has to be related to the distribution of the clonogenic cell density (CCD). The main aim of this work is to provide the means to calculate the optimal prescription dose in a relative inhomogeneous dose distribution. To achieve this, the prescription dose has to be assigned to obtain the same tumor control probability (TCP) as the ideal homogeneous distribution, taking into account different CCDs in different PTVs (i.e. visible and subclinical regions). An adapted formulation of the linear-quadratic model, within the F-factor formalism, has been derived to preserve a chosen TCP value for the whole target volume. The F-factor has been investigated to show its potential applications in clinical practice.

Comparison of IMRT planning with two-step and one-step optimization: a strategy for improving therapeutic gain and reducing the integral dose

The aim of this study was to evaluate the effectiveness and efficiency in inverse IMRT planning of one-step optimization with the step-and-shoot (SS) technique as compared to traditional two-step optimization using the sliding windows (SW) technique. The Pinnacle IMRT TPS allows both one-step and two-step approaches. The same beam setup for five head-and-neck tumor patients and dose-volume constraints were applied for all optimization methods. Two-step plans were produced converting the ideal fluence with or without a smoothing filter into the SW sequence. One-step plans, based on direct machine parameter optimization (DMPO), had the maximum number of segments per beam set at 8, 10, 12, producing a directly deliverable sequence. Moreover, the plans were generated whether a split-beam was used or not. Total monitor units (MUs), overall treatment time, cost function and dose-volume histograms (DVHs) were estimated for each plan. PTV conformality and homogeneity indexes and normal tissue complication probability (NTCP) that are the basis for improving therapeutic gain, as well as non-tumor integral dose (NTID), were evaluated. A two-sided t-test was used to compare quantitative variables. All plans showed similar target coverage. Compared to two-step SW optimization, the DMPO-SS plans resulted in lower MUs (20%), NTID (4%) as well as NTCP values. Differences of about 15-20% in the treatment delivery time were registered. DMPO generates less complex plans with identical PTV coverage, providing lower NTCP and NTID, which is expected to reduce the risk of secondary cancer. It is an effective and efficient method and, if available, it should be favored over the two-step IMRT planning.

A mathematical approach for evaluating the influence of dose heterogeneity on TCP for prostate cancer brachytherapy treatment

The low-dose-rate brachytherapy technique has proven suitable for the management of prostate cancer. However, published data generally report the clinical outcome and the minimum peripheral dose (mPD) to the target volume and not the actual dose distribution in patients. To this end, modern guidelines recommend the use of specific dose and volume indices describing dose distribution throughout the target. The introduction of a method, based on the standard linear quadratic model and Poisson statistics, entitled the F-factor allows the TCP from different DVHs to be calculated, by using the TCP from a uniform dose distribution as the reference. The F-factor sensitivity against radiobiological parameters and influence of the DVH were evaluated. We applied the F-formula on the post-plan DVHs of 58 patients treated with (125)I permanent seed implant brachytherapy for localized prostate cancer. F shows a strong correlation with dosimetric parameters already reported as significant predictors of the biochemical outcome.

A modified hypoxia-based TCP model to investigate the clinical outcome of stereotactic hypofractionated regimes for early stage non-small-cell lung cancer (NSCLC).

PURPOSE Stereotactic body radiotherapy (SBRT) has been applied to lung tumors at different stages and sizes with good local tumor control (LC) rates. The linear quadratic model (LQM), in its basic formulation, does not seem to be appropriate to describe the response to radiotherapy for clinical trials, based on a few fractions. Thus, the main aim of this work was to develop a model, which takes into account the hypoxic cells and their reoxygenation. METHODS A parameter named B has been introduced in a modified tumor control probability (TCP) from LQM and linear-quadratic-linear model (LQLM), and represents the fraction of hypoxic cells that survive and become oxygenated after each irradiation. Based on published trials evaluating LC at 3 yr (LC3), values of B were obtained by maximum likelihood minimization between predicted TCP and clinical LC3. Two oxygen enhancement ratio (OER) parameter sets (1 and 2) from literature have been adopted to calculate the B-factors. Initial hypoxic cell fractions (η(h)) from 0.05 to 0.50 were assumed. Log-likelihood (L) and Akaike information criterion (AIC) were determined in an independent clinical validation dataset. RESULTS The B-values of modified TCPs spanned the whole interval from 0 to 1, depending on the fractionation scheme (number of fractions and dose/fraction), showing a maximum (close to 1) at doses/fraction of 8-12 Gy. The B-values calculated using the OER parameter set 1 exhibited a smoother falloff than set 2. An analytical expression was derived to describe the B-values dependence on the fractionation scheme. The R(2)-adjusted values varied from 0.63 to 0.67 for LQ models and OER set 1 and from 0.75 to 0.78 for LQ model and OER set 2. Lower values of R(2)-adjusted were found for LQLM and both OER sets. L and AIC, calculated using a fraction of η(h) = 0.15 and the B-value from the authors analytical expression were higher than for other η(h)-values, irrespective of model or OER set. CONCLUSIONS The authors model allows to predict the clinical outcome associated with SBRT treatment, taking into account both direct killing and indirect vasculature or stromal damage.PURPOSE Stereotactic body radiotherapy (SBRT) has been applied to lung tumors at different stages and sizes with good local tumor control (LC) rates. The linear quadratic model (LQM), in its basic formulation, does not seem to be appropriate to describe the response to radiotherapy for clinical trials, based on a few fractions. Thus, the main aim of this work was to develop a model, which takes into account the hypoxic cells and their reoxygenation. METHODS A parameter namedB has been introduced in a modified tumor control probability (TCP) from LQM and linear-quadratic-linear model (LQLM), and represents the fraction of hypoxic cells that survive and become oxygenated after each irradiation. Based on published trials evaluating LC at 3 yr (LC3), values of B were obtained by maximum likelihood minimization between predicted TCP and clinical LC3. Two oxygen enhancement ratio (OER) parameter sets (1 and 2) from literature have been adopted to calculate the B-factors. Initial hypoxic cell fractions (ηh ) from 0.05 to 0.50 were assumed. Log-likelihood (L) and Akaike information criterion (AIC) were determined in an independent clinical validation dataset. RESULTS TheB-values of modified TCPs spanned the whole interval from 0 to 1, depending on the fractionation scheme (number of fractions and dose/fraction), showing a maximum (close to 1) at doses/fraction of 8-12 Gy. The B-values calculated using the OER parameter set 1 exhibited a smoother falloff than set 2. An analytical expression was derived to describe the B-values dependence on the fractionation scheme. The R2 -adjusted values varied from 0.63 to 0.67 for LQ models and OER set 1 and from 0.75 to 0.78 for LQ model and OER set 2. Lower values of R2 -adjusted were found for LQLM and both OER sets. L and AIC, calculated using a fraction of ηh = 0.15 and the B-value from the authors analytical expression were higher than for other ηh -values, irrespective of model or OER set. CONCLUSIONS The authors model allows to predict the clinical outcome associated with SBRT treatment, taking into account both direct killing and indirect vasculature or stromal damage.

Role of the parameters involved in the plan optimization based on the generalized equivalent uniform dose and radiobiological implications

We investigated the role and the weight of the parameters involved in the intensity modulated radiation therapy (IMRT) optimization based on the generalized equivalent uniform dose (gEUD) method, for prostate and head-and-neck plans. We systematically varied the parameters (gEUDmax and weight) involved in the gEUD-based optimization of rectal wall and parotid glands. We found that the proper value of weight factor, still guaranteeing planning treatment volumes coverage, produced similar organs at risks dose-volume (DV) histograms for different gEUDmax with fixed a=1. Most of all, we formulated a simple relation that links the reference gEUDmax and the associated weight factor. As secondary objective, we evaluated plans obtained with the gEUD-based optimization and ones based on DV criteria, using the normal tissue complication probability (NTCP) models. gEUD criteria seemed to improve sparing of rectum and parotid glands with respect to DV-based optimization: the mean dose, the V40 and V50 values to the rectal wall were decreased of about 10%, the mean dose to parotids decreased of about 20-30%. But more than the OARs sparing, we underlined the halving of the OARs optimization time with the implementation of the gEUD-based cost function. Using NTCP models we enhanced differences between the two optimization criteria for parotid glands, but no for rectum wall.

Monitoring of people and workers exposure to the electric, magnetic and electromagnetic fields in an Italian national cancer Institute

BackgroundThe paper reports the electric, magnetic and electromagnetic fields (emf) measurements carried out in the Regina Elena National Cancer Institute (NCI). Several devices, used in diagnostics and in medical cures, can represent sources of emf for the workers and for the public subjected to the treatments. The aim is to evaluate their exposition, in order to assess the compliance with the law.MethodsThe investigations have been carried out in the departments of: intensive care, physiotherapy, MR presstherapy and in the surgical rooms. The measurements have been performed using broad band probes in the frequency ranges 5 Hz÷30 kHz and 100 kHz-3 GHz.ResultsThe variability of the magnetic induction (B(μT)) levels is between 0,05 μT and 80 μT. The statistical distribution shows that most of the measurements are in the range 0,05<B = 0,5 μT and the 89% of the B(μT) levels are within the 3 μT.ConclusionThe measurement of the emf levels in the NCI is recommended because of the presence of the oncological patients; their long stay near the equipments and their day-long exposure represent additional risk factors for which a prudent avoidance strategy have to de adopted.

Self-organizing ability and living systems.

Abstract In the present paper we have emphasized the actual impossibility to unify thermodynamics and systemology under the same physical formalism. As a consequence, 2 non-isomorphic descriptions of living beings must be given, each of them embracing a number of properties (or phenomena) that, in turn, the other one cannot deal with. We suggest to join the thermodynamic and the systemological approaches by means of a “complementarity relationship”, into a global function Ω whose features are examined with some detail. Such a function is used to depict self-organizing ability; its value characterizes the state of the system. Furthermore, it has both “self-reproduction” and “hierarchical” attributes. Because of considerations given in the text, function Ω is defined in the form of a postulate.

Twenty years of radiobiology in clinical practice: the Italian contribution

Aims and background To present the Italian state-of-the-art contribution to radiobiology of external beam radiotherapy, brachytherapy, and radionuclide radiotherapy. Methods and study design A survey of the literature was carried out, using PubMed, by some independent researchers of the Italian group of radiobiology. Each paper was reviewed by researchers of centers not comprising its authors. The survey was limited to papers in English published over the last 20 years, written by Italian investigators or in Italian institutions, excluding review articles. Results A total of 135 papers have been published in journals with an impact factor, with an increase in the number of published papers over time, for external beam radiotherapy rather than radionuclide radiotherapy. The quantity and quality of the papers researched constitutes a proof of the enduring interest in clinical radiobiology among Italian investigators. Conclusions The survey could be useful to individuate expert partners for an Italian network on clinical radiobiology, addressing future collaborative investigations.

SU‐FF‐T‐129: Comparison of IMRT Planning with Two‐Step and One‐Step Optimization: Strategy for Improving Therapeutic Gain Reducing Integral Dose

Purpose: Intensity‐modulated radiotherapy(IMRT) plans are often complex and time consuming both in the optimization and delivery phase, the latter increasing the potential for dosimetric errors. The purpose of this study is to evaluate the effectiveness and efficiency of one‐step optimization with step‐and‐shoot technique as compared to conventional two with sliding windows technique optimization in inverse IMRT planning. Material and methods: The approach generally employed to generate the photon fluence maps is a two‐step process: first the optimization problem is solved generating an ideal matrix of photon fluence, then the fluence profiles are converted into a deliverablephoton fluences through a sequencer software using step‐and shoot or sliding window modality of multi‐leaf collimators. Machine parameters can be considered directly in direct machine parameter optimization (DMPO) or in the conversion phase in the two step approach. The Pinnacle IMRT TPS allows both approach. One‐step plans had the maximum number of segments set at 50, 70, 90. Two‐step plans were produced using ideal fluence, with or without smooth filter, converted into a sliding windows sequence. Moreover, the plans were generated allowing or not the split of the beams. Results: All plans showed similar target coverage. Compared to traditional two‐step optimization and dynamic modality, DMPO plans resulted in lower MUs, and lower doses to sensitive structures as well as Normal Tissue Complication Probability. The total MUs and the integral dose were lower for plans with the splitted than the no splitted beams. Conclusion: One‐step optimization is an effective and efficient method for simplifying IMRT plans.