A joint physics and radiobiology DREAM team vision - Towards better response prediction models to advance radiotherapy.

Radiotherapy developed empirically through experience balancing tumour control and normal tissue toxicities. Early simple mathematical models formalized this practical knowledge and enabled effective cancer treatment to date. Remarkable advances in technology, computing, and experimental biology now create opportunities to incorporate this knowledge into enhanced computational models. The ESTRO DREAM (Dose Response, Experiment, Analysis, Modelling) workshop brought together experts across disciplines to pursue the vision of personalized radiotherapy for optimal outcomes through advanced modelling. The ultimate vision is leveraging quantitative models dynamically during therapy to ultimately achieve truly adaptive and biologically guided radiotherapy at the population as well as individual patient-based levels. This requires the generation of models that inform response-based adaptations, individually optimized delivery and enable biological monitoring to provide decision support to clinicians. The goal is expanding to models that can drive the realization of personalized therapy for optimal outcomes. This position paper provides their propositions that describe how innovations in biology, physics, mathematics, and data science including AI could inform models and improve predictions. It consolidates the DREAM team's consensus on scientific priorities and organizational requirements. Scientifically, it stresses the need for rigorous, multifaceted model development, comprehensive validation and clinical applicability and significance. Organizationally, it reinforces the prerequisites of interdisciplinary research and collaboration between physicians, medical physicists, radiobiologists, and computational scientists throughout model development. Solely by a shared understanding of clinical needs, biological mechanisms, and computational methods, more informed models can be created. Future research environment and support must facilitate this integrative method of operation across multiple disciplines.

Monte Carlo verification of the holder correction factors for the radiophotoluminescent glass dosimeter used by the IAEA in international dosimetry audits.

The International Atomic Energy Agency (IAEA), jointly with the World Health Organization (WHO), has operated a postal dosimetry audit program for radiotherapy centers worldwide since 1969. In 2017 the IAEA introduced a new methodology based on radiophotoluminescent dosimetry (RPLD) for these audits. The detection system consists of a phosphate glass dosimeter inserted in a plastic capsule that is kept in measuring position with a PMMA holder during irradiation. Correction factors for this holder were obtained using experimental methods. In this work these methods are described and the resulting factors are verified by means of Monte Carlo simulation with the general-purpose code PENELOPE for a range of photon beam qualities relevant in radiotherapy. The study relies on a detailed geometrical representation of the experimental setup. Various photon beams were obtained from faithful modeling of the corresponding linacs. Monte Carlo simulation transport parameters are selected to ensure subpercent accuracy. The simulated correction factors fall in the interval 1.005-1.008 (±0.2%), with deviations with respect to experimental values not larger than 0.2(2)%. This study corroborates the validity of the holder correction factors currently used for the IAEA audits.

Computation of the electron beam quality [Formula: see text] factors for the NE2571, NE2571A and NE2581A thimble ionization chambers using PENELOPE.

The quality correction factor [Formula: see text] for electron beams was calculated for three thimble ionization chambers, namely, NE2571, NE2571A and NE2581A. The Monte Carlo code PENELOPE was used to estimate the overall correction factor fc,Q of these chambers for electron beams with nominal energies ranging between 6 and 22MeV, corresponding to a Varian Clinac 2100 C/D. A 60Co beam was used as reference quality Q0. Also eight monoenergetic electron beams reproducing the quality index R50 of the Clinac beams were considered. The [Formula: see text] factors were calculated as the ratio between fc,Q and [Formula: see text] . Those obtained for the NE2571 ionization chamber show a nice agreement with those calculated by Muir and Rogers with EGSnrc. As it occurred to other ionization chambers analyzed in previous works, the [Formula: see text] factors found for the monoenergetic beams are larger (smaller) than those corresponding to the Clinac beams at low (high) R50 values, the differences being slightly above 0.5%. Finally, the [Formula: see text] factors obtained in the case of the NE2571A chamber are systematically ∼0.5% below those of its predecessor chamber, the NE2571.

A geometrical model for the Monte Carlo simulation of the TrueBeam linac.

Monte Carlo simulation of linear accelerators (linacs) depends on the accurate geometrical description of the linac head. The geometry of the Varian TrueBeam linac is not available to researchers. Instead, the company distributes phase-space files of the flattening-filter-free (FFF) beams tallied at a plane located just upstream of the jaws. Yet, Monte Carlo simulations based on third-party tallied phase spaces are subject to limitations. In this work, an experimentally based geometry developed for the simulation of the FFF beams of the Varian TrueBeam linac is presented. The Monte Carlo geometrical model of the TrueBeam linac uses information provided by Varian that reveals large similarities between the TrueBeam machine and the Clinac 2100 downstream of the jaws. Thus, the upper part of the TrueBeam linac was modeled by introducing modifications to the Varian Clinac 2100 linac geometry. The most important of these modifications is the replacement of the standard flattening filters by ad hoc thin filters. These filters were modeled by comparing dose measurements and simulations. The experimental dose profiles for the 6 MV and 10 MV FFF beams were obtained from the Varian Golden Data Set and from in-house measurements performed with a diode detector for radiation fields ranging from 3 × 3 to 40 × 40 cm(2) at depths of maximum dose of 5 and 10 cm. Indicators of agreement between the experimental data and the simulation results obtained with the proposed geometrical model were the dose differences, the root-mean-square error and the gamma index. The same comparisons were performed for dose profiles obtained from Monte Carlo simulations using the phase-space files distributed by Varian for the TrueBeam linac as the sources of particles. Results of comparisons show a good agreement of the dose for the ansatz geometry similar to that obtained for the simulations with the TrueBeam phase-space files for all fields and depths considered, except for the 40 × 40 cm(2) field where the ansatz geometry was able to reproduce the measured dose more accurately. Our approach overcomes some of the limitations of using the Varian phase-space files. It makes it possible to: (i) adapt the initial beam parameters to match measured dose profiles; (ii) reduce the statistical uncertainty to arbitrarily low values; and (iii) assess systematic uncertainties (type B) by using different Monte Carlo codes. One limitation of using phase-space files that is retained in our model is the impossibility of performing accurate absolute dosimetry simulations because the geometrical description of the TrueBeam ionization chamber remains unknown.

Technical note: Influence of the phantom material on the absorbed-dose energy dependence of the EBT3 radiochromic film for photons in the energy range 3 keV-18 MeV.

PURPOSE: Water is the reference medium for radiation therapy dosimetry, but for film dosimetry it is more practical to use a solid phantom. As the composition of solid phantoms differs from that of water, the energy dependence of film exposed within solid phantoms may also differ. The energy dependence of a radiochromic film for a given beam quality Q (energy for monoenergetic beams) has two components: the intrinsic energy dependence and the absorbed-dose energy dependence f(Q), the latter of which can be calculated through a Monte Carlo simulation of radiation transport. The authors used Monte Carlo simulations to study the influence of the phantom material on the f(Q) of the EBT3 radiochromic film (Ashland Specialty Ingredients, Wayne, NJ) for photon beams with energies between 3 keV and 18 MeV. METHODS: All simulations were carried out with the general-purpose Monte Carlo code penelope 2011. The geometrical model consisted of a cylindrical phantom, with the film positioned at different depths depending on the initial photon energy. The authors simulated monoenergetic parallel photon beams and x-ray beams from a superficial therapy system. To validate their choice of simulation parameters, they also calculated f(Q) for older film models, EBT and EBT2, comparing with published results. In addition to water, they calculated f(Q) of the EBT3 film for solid phantom materials commonly used for film dosimetry: RW1 and RW3 (PTW-Freiburg, Freiburg, Germany), Solid Water (Gammex-RMI, Madison, WI), and PMMA. Finally, they combined their calculated f(Q) with published overall energy response data to obtain the intrinsic energy dependence of the EBT3 film in water. RESULTS: The calculated f(Q) for EBT and EBT2 films was statistically compatible with previously published data. Between 10 keV and 18 MeV, the variation found in f(Q) of the EBT3 film for water was within 2.3%, with a standard statistical uncertainty less than 1%. If the quantity dose-to-water in the phantom is considered, which is the common practice in radiation dosimetry, the maximum difference of energy dependence for the solid phantoms with respect to water is about 6%, at an energy of 50 keV. CONCLUSIONS: The EBT3 film shows a reasonably constant absorbed-dose energy dependence when irradiated in water. If the dose-to-water in the phantom is considered, the maximum difference of EBT3 film energy dependence with the solid phantoms studied with respect to water is about 6% (at an energy of 50 keV). The reported overall energy dependence of the EBT3 film in water at energies below 100 keV is mainly due to the intrinsic energy dependence.

Electron beam quality k(Q,Q0) factors for various ionization chambers: a Monte Carlo investigation with PENELOPE.

In this work we calculate the beam quality correction factor k(Q,Q0) for various plane-parallel ionization chambers. A set of Monte Carlo calculations using the code PENELOPE/PENEASY have been carried out to calculate the overall correction factor f(c,Q) for eight electron beams corresponding to a Varian Clinac 2100 C/D, with nominal energies ranging between 6 MeV and 22 MeV, for a (60)Co beam, that has been used as the reference quality Q0 and also for eight monoenergetic electron beams reproducing the quality index R50 of the Clinac beams. Two field sizes, 10 × 10 cm(2) and 20 × 20 cm(2) have been considered. The k(Q,Q0) factors have been calculated as the ratio between f(c,Q) and f(c,Q0). Values for the Exradin A10, A11, A11TW, P11, P11TW, T11 and T11TW ionization chambers, manufactured by Standard Imaging, as well as for the NACP-02 have been obtained. The results found with the Clinac beams for the two field sizes analyzed show differences below 0.6%, even in the case of the higher energy electron beams. The k(Q,Q0) values obtained with the Clinac beams are 1% larger than those found with the monoenergetic beams for the higher energies, above 12 MeV. This difference can be ascribed to secondary photons produced in the linac head and the air path towards the phantom. Contrary to what was quoted in a previous work (Sempau et al 2004 Phys. Med. Biol. 49 4427-44), the beam quality correction factors obtained with the complete Clinac geometries and with the monoenergetic beams differ significantly for energies above 12 MeV. Material differences existing between chambers that have the same geometry produce non-negligible modifications in the value of these correction factors.

Monte Carlo study for designing a dedicated "D"-shaped collimator used in the external beam radiotherapy of retinoblastoma patients.

PURPOSE: Retinoblastoma is the most common intraocular malignancy in the early childhood. Patients treated with external beam radiotherapy respond very well to the treatment. However, owing to the genotype of children suffering hereditary retinoblastoma, the risk of secondary radio-induced malignancies is high. The University Hospital of Essen has successfully treated these patients on a daily basis during nearly 30 years using a dedicated "D"-shaped collimator. The use of this collimator that delivers a highly conformed small radiation field, gives very good results in the control of the primary tumor as well as in preserving visual function, while it avoids the devastating side effects of deformation of midface bones. The purpose of the present paper is to propose a modified version of the "D"-shaped collimator that reduces even further the irradiation field with the scope to reduce as well the risk of radio-induced secondary malignancies. Concurrently, the new dedicated "D"-shaped collimator must be easier to build and at the same time produces dose distributions that only differ on the field size with respect to the dose distributions obtained by the current collimator in use. The scope of the former requirement is to facilitate the employment of the authors' irradiation technique both at the authors' and at other hospitals. The fulfillment of the latter allows the authors to continue using the clinical experience gained in more than 30 years. METHODS: The Monte Carlo code PENELOPE was used to study the effect that the different structural elements of the dedicated "D"-shaped collimator have on the absorbed dose distribution. To perform this study, the radiation transport through a Varian Clinac 2100 C/D operating at 6 MV was simulated in order to tally phase-space files which were then used as radiation sources to simulate the considered collimators and the subsequent dose distributions. With the knowledge gained in that study, a new, simpler, "D"-shaped collimator is proposed. RESULTS: The proposed collimator delivers a dose distribution which is 2.4 cm wide along the inferior-superior direction of the eyeball. This width is 0.3 cm narrower than that of the dose distribution obtained with the collimator currently in clinical use. The other relevant characteristics of the dose distribution obtained with the new collimator, namely, depth doses at clinically relevant positions, penumbrae width, and shape of the lateral profiles, are statistically compatible with the results obtained for the collimator currently in use. CONCLUSIONS: The smaller field size delivered by the proposed collimator still fully covers the planning target volume with at least 95% of the maximum dose at a depth of 2 cm and provides a safety margin of 0.2 cm, so ensuring an adequate treatment while reducing the irradiated volume.

PRIMO: a graphical environment for the Monte Carlo simulation of Varian and Elekta linacs.

BACKGROUND: The accurate Monte Carlo simulation of a linac requires a detailed description of its geometry and the application of elaborate variance-reduction techniques for radiation transport. Both tasks entail a substantial coding effort and demand advanced knowledge of the intricacies of the Monte Carlo system being used. METHODS: PRIMO, a new Monte Carlo system that allows the effortless simulation of most Varian and Elekta linacs, including their multileaf collimators and electron applicators, is introduced. PRIMO combines (1) accurate physics from the PENELOPE code, (2) dedicated variance-reduction techniques that significantly reduce the computation time, and (3) a user-friendly graphical interface with tools for the analysis of the generated data. PRIMO can tally dose distributions in phantoms and computerized tomographies, handle phase-space files in IAEA format, and import structures (planning target volumes, organs at risk) in the DICOM RT-STRUCT standard. RESULTS: A prostate treatment, conformed with a high definition Millenium multileaf collimator (MLC 120HD) from a Varian Clinac 2100 C/D, is presented as an example. The computation of the dose distribution in 1.86×3.00×1.86 mm3 voxels with an average 2% standard statistical uncertainty, performed on an eight-core Intel Xeon at 2.67 GHz, took 1.8 h-excluding the patient-independent part of the linac, which required 3.8 h but it is simulated only once. CONCLUSION: PRIMO is a self-contained user-friendly system that facilitates the Monte Carlo simulation of dose distributions produced by most currently available linacs. This opens the door for routine use of Monte Carlo in clinical research and quality assurance purposes. It is free software that can be downloaded from http://www.primoproject.net.

Accurate estimation of dose distributions inside an eye irradiated with 106Ru plaques.

BACKGROUND: Irradiation of intraocular tumors requires dedicated techniques, such as brachytherapy with (106)Ru plaques. The currently available treatment planning system relies on the assumption that the eye is a homogeneous water sphere and on simplified radiation transport physics. However, accurate dose distributions and their assessment demand better models for both the eye and the physics. METHODS: The Monte Carlo code PENELOPE, conveniently adapted to simulate the beta decay of (106)Ru over (106)Rh into (106)Pd, was used to simulate radiation transport based on a computerized tomography scan of a patient's eye. A detailed geometrical description of two plaques (models CCA and CCB) from the manufacturer BEBIG was embedded in the computerized tomography scan. RESULTS: The simulations were firstly validated by comparison with experimental results in a water phantom. Dose maps were computed for three plaque locations on the eyeball. From these maps, isodose curves and cumulative dose-volume histograms in the eye and for the structures at risk were assessed. For example, it was observed that a 4-mm anterior displacement with respect to a posterior placement of a CCA plaque for treating a posterior tumor would reduce from 40 to 0% the volume of the optic disc receiving more than 80 Gy. Such a small difference in anatomical position leads to a change in the dose that is crucial for side effects, especially with respect to visual acuity. The radiation oncologist has to bring these large changes in absorbed dose in the structures at risk to the attention of the surgeon, especially when the plaque has to be positioned close to relevant tissues. CONCLUSION: The detailed geometry of an eye plaque in computerized and segmented tomography of a realistic patient phantom was simulated accurately. Dose-volume histograms for relevant anatomical structures of the eye and the orbit were obtained with unprecedented accuracy. This represents an important step toward an optimized brachytherapy treatment of ocular tumors.

Retinoblastoma external beam photon irradiation with a special 'D'-shaped collimator: a comparison between measurements, Monte Carlo simulation and a treatment planning system calculation.

Retinoblastoma is the most common eye tumour in childhood. According to the available long-term data, the best outcome regarding tumour control and visual function has been reached by external beam radiotherapy. The benefits of the treatment are, however, jeopardized by a high incidence of radiation-induced secondary malignancies and the fact that irradiated bones grow asymmetrically. In order to better exploit the advantages of external beam radiotherapy, it is necessary to improve current techniques by reducing the irradiated volume and minimizing the dose to the facial bones. To this end, dose measurements and simulated data in a water phantom are essential. A Varian Clinac 2100 C/D operating at 6 MV is used in conjunction with a dedicated collimator for the retinoblastoma treatment. This collimator conforms a 'D'-shaped off-axis field whose irradiated area can be either 5.2 or 3.1 cm(2). Depth dose distributions and lateral profiles were experimentally measured. Experimental results were compared with Monte Carlo simulations' run with the penelope code and with calculations performed with the analytical anisotropic algorithm implemented in the Eclipse treatment planning system using the gamma test. penelope simulations agree reasonably well with the experimental data with discrepancies in the dose profiles less than 3 mm of distance to agreement and 3% of dose. Discrepancies between the results found with the analytical anisotropic algorithm and the experimental data reach 3 mm and 6%. Although the discrepancies between the results obtained with the analytical anisotropic algorithm and the experimental data are notable, it is possible to consider this algorithm for routine treatment planning of retinoblastoma patients, provided the limitations of the algorithm are known and taken into account by the medical physicist and the clinician. Monte Carlo simulation is essential for knowing these limitations. Monte Carlo simulation is required for optimizing the treatment technique and the dedicated collimator.

A combined approach of variance-reduction techniques for the efficient Monte Carlo simulation of linacs.

A method based on a combination of the variance-reduction techniques of particle splitting and Russian roulette is presented. This method improves the efficiency of radiation transport through linear accelerator geometries simulated with the Monte Carlo method. The method named as 'splitting-roulette' was implemented on the Monte Carlo code [Formula: see text] and tested on an Elekta linac, although it is general enough to be implemented on any other general-purpose Monte Carlo radiation transport code and linac geometry. Splitting-roulette uses any of the following two modes of splitting: simple splitting and 'selective splitting'. Selective splitting is a new splitting mode based on the angular distribution of bremsstrahlung photons implemented in the Monte Carlo code [Formula: see text]. Splitting-roulette improves the simulation efficiency of an Elekta SL25 linac by a factor of 45.

A liquid-filled ionization chamber for high precision relative dosimetry.

Radiosurgery and intensity modulated radiation therapy (IMRT) treatments are based on the delivery of narrow and/or irregularly shaped megavoltage photon beams. This kind of beams present both lack of charged particle equilibrium and steep dose gradients. Quality assurance (QA) measurements involved in these techniques must therefore be carried out with a dosimeter featuring high small volume. In order to obtain a good signal to noise ratio, a relatively dense material is needed as active medium. Non-polar organic liquids were proposed as active mediums with both good tissue equivalence and showing high signal to noise ratio. In this work, a liquid-filled ionization chamber is presented. Some results acquired with this detector in relative dosimetry are studied and compared with results obtained with unshielded diode. Medium-term stability measurements were also carried out and its results are shown. The liquid-filled ionization chamber presented here shows its ability to perform profile measurements and penumbrae determination with excellent accuracy. The chamber features a proper signal stability over the period studied.

Ant colony algorithm implementation in electron and photon Monte Carlo transport: application to the commissioning of radiosurgery photon beams.

PURPOSE: In this work, the authors describe an approach which has been developed to drive the application of different variance-reduction techniques to the Monte Carlo simulation of photon and electron transport in clinical accelerators. METHODS: The new approach considers the following techniques: Russian roulette, splitting, a modified version of the directional bremsstrahlung splitting, and the azimuthal particle redistribution. Their application is controlled by an ant colony algorithm based on an importance map. RESULTS: The procedure has been applied to radiosurgery beams. Specifically, the authors have calculated depth-dose profiles, off-axis ratios, and output factors, quantities usually considered in the commissioning of these beams. The agreement between Monte Carlo results and the corresponding measurements is within approximately 3%/0.3 mm for the central axis percentage depth dose and the dose profiles. The importance map generated in the calculation can be used to discuss simulation details in the different parts of the geometry in a simple way. The simulation CPU times are comparable to those needed within other approaches common in this field. CONCLUSIONS: The new approach is competitive with those previously used in this kind of problems (PSF generation or source models) and has some practical advantages that make it to be a good tool to simulate the radiation transport in problems where the quantities of interest are difficult to obtain because of low statistics.

Determination of the optimal statistical uncertainty to perform electron-beam Monte Carlo absorbed dose estimation in the target volume.

PURPOSE OF STUDY: Monte Carlo based treatment planning system are known to be more accurate than analytical methods for performing absorbed dose estimation, particularly in and near heterogeneities. However, the required computation time can still be an issue. The present study focused on the determination of the optimum statistical uncertainty in order to minimise computation time while keeping the reliability of the absorbed dose estimation in treatments planned with electron-beams. MATERIALS AND METHODS: Three radiotherapy plans (medulloblastoma, breast and gynaecological) were used to investigate the influence of the statistical uncertainty of the absorbed dose on the target volume dose-volume histograms (spinal cord, intramammary nodes and pelvic lymph nodes, respectively). RESULTS: The study of the dose-volume histograms showed that for statistical uncertainty levels (1 S.D.) above 2 to 3%, the standard deviation of the mean dose in the target volume calculated from the dose-volume histograms increases by at least 6%, reflecting the gradual flattening of the dose-volume histograms. CONCLUSIONS: This work suggests that, in clinical context, Monte Carlo based absorbed dose estimations should be performed with a maximum statistical uncertainty of 2 to 3%.

Fast Monte Carlo simulation on a voxelized human phantom deformed to a patient.

PURPOSE: A method for performing fast simulations of absorbed dose using a patient's computerized tomography (CT) scan without explicitly relying on a calibration curve is presented. METHODS: The method is based on geometrical deformations performed on a standard voxelized human phantom. This involves spatially transforming the human phantom to align it with the patient CT image. Since the chemical composition and density of each voxel are given in the phantom data, a calibration curve is not used in the proposed method. For this study, the Monte Carlo (MC) code PENELOPE has been used as the simulation of reference. The results obtained with PENELOPE simulations are compared to those obtained with PENFAST and with the collapsed cone convolution algorithm implemented in a commercial treatment planning system. RESULTS: The comparisons of the absorbed doses calculated with the different algorithms on two patient CTs and the corresponding deformed phantoms show a maximum distance to agreement of 2 mm, and in general, the obtained absorbed dose distributions are compatible within the reached statistical uncertainty. The validity of the deformation method for a broad range of patients is shown using MC simulations in random density phantoms. A PENFAST simulation of a 6 MV photon beam impinging on a patient CT reaches 2% statistical uncertainty in the absorbed dose, in a 0.1 cm3 voxel along the central axis, in 10 min running on a single core of a 2.8 GHz CPU. CONCLUSIONS: The proposed method of the absorbed dose calculation in a deformed voxelized phantom allows for dosimetric studies in the geometry of a patient CT scan. This is due to the fact that the chemical composition and material density of the phantom are known. Furthermore, simulation using the phantom geometry can provide dosimetric information for each organ. The method can be used for quality assurance procedures. In relation to PENFAST, it is shown that a purely condensed-history algorithm (class I) can be used for absorbed dose estimation in patient CTs.

Evaluation of the material assignment method used by a Monte Carlo treatment planning system.

An evaluation of the conversion process from Hounsfield units (HU) to material composition in computerised tomography (CT) images, employed by the Monte Carlo based treatment planning system ISOgray (DOSIsoft), is presented. A boundary in the HU for the material conversion between "air" and "lung" materials was determined based on a study using 22 patients. The dosimetric consequence of the new boundary was quantitatively evaluated for a lung patient plan.

Comparison between PENELOPE and electron Monte Carlo simulations of electron fields used in the treatment of conjunctival lymphoma.

For the treatment of conjunctival lymphoma in the early stages, external beam radiotherapy offers a curative approach. Such treatment requires the use of highly conformed small radiation beams. The beam size is so small that even advanced treatment planning systems have difficulties in calculating dose distributions. One possible approach for optimizing the treatment technique and later performing treatment planning is by means of full Monte Carlo (MC) simulations. In this paper, we compare experimental absorbed dose profiles obtained with a collimator used at the University Hospital Essen, with MC simulations done with the general-purpose radiation transport code PENELOPE. The collimator is also simulated with the hybrid MC code electron Monte Carlo (eMC) implemented in the commercial treatment planning system Eclipse (Varian). The results obtained with PENELOPE have a maximum difference with experimental data of 2.3%, whereas the eMC code differs systematically from the experimental data about 7% in the penumbra tails. We also show that PENELOPE simulations are able to obtain absorbed dose maps with an equivalent statistical uncertainty to the one found with eMC in similar CPU times.

Efficient Monte Carlo simulation of multileaf collimators using geometry-related variance-reduction techniques.

A technique for accelerating the simulation of multileaf collimators with Monte Carlo methods is presented. This technique, which will be referred to as the movable-skin method, is based on geometrical modifications that do not alter the physical shape of the leaves, but that affect the logical way in which the Monte Carlo code processes the geometry. Zones of the geometry from which secondary radiation can emerge are defined as skins and the radiation transport throughout these zones is simulated accurately, while transport in non-skin zones is modelled approximately. The skins method is general and can be applied to most of the radiation transport Monte Carlo codes used in radiotherapy. The code AUTOLINAC for the automatic generation of the geometry file and the physical parameters required in a simulation of a linac with the Monte Carlo code PENELOPE is also introduced. This code has a modularized library of all Varian Clinac machines with their multileaf collimators and electron applicators. AUTOLINAC automatically determines the position of skins and the parameter values employed for other variance-reduction techniques that are adequate for the simulation of a linac. Using the adaptive variance-reduction techniques presented here it is possible to simulate with PENELOPE an entire linac with a fully closed multileaf collimator in two hours. For this benchmark a single core of a 2.8 GHz processor was used and 2% statistical uncertainty (1sigma) of the absorbed dose in water was reached with a voxel size of 2 x 2 x 2 mm(3). Several configurations of the multileaf collimator were simulated and the results were found to be in excellent agreement with experimental measurements.

Quantum monte carlo algorithm based on two-body density functional theory for fermionic many-body systems: application to 3He.

We construct a quantum Monte Carlo algorithm for interacting fermions using the two-body density as the fundamental quantity. The central idea is mapping the interacting fermionic system onto an auxiliary system of interacting bosons. The correction term is approximated using correlated wave functions for the interacting system, resulting in an effective potential that represents the nodal surface. We calculate the properties of 3He and find good agreement with experiment and with other theoretical work. In particular, our results for the total energy agree well with other calculations where the same approximations were implemented but the standard quantum Monte Carlo algorithm was used.

Higher order and infinite Trotter-number extrapolations in path integral Monte Carlo.

Improvements beyond the primitive approximation in the path integral Monte Carlo method are explored both in a model problem and in real systems. Two different strategies are studied: The Richardson extrapolation on top of the path integral Monte Carlo data and the Takahashi-Imada action. The Richardson extrapolation, mainly combined with the primitive action, always reduces the number-of-beads dependence, helps in determining the approach to the dominant power law behavior, and all without additional computational cost. The Takahashi-Imada action has been tested in two hard-core interacting quantum liquids at low temperature. The results obtained show that the fourth-order behavior near the asymptote is conserved, and that the use of this improved action reduces the computing time with respect to the primitive approximation.