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.

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.

An indirect in vivo dosimetry system for ocular proton therapy.

Secondary radiation, particularly neutron radiation, is a cause of concern in proton therapy. However, one can take advantage of its presence by using it to retrieve useful information on the primary proton beam. At the Centre Antoine Lacassagne the secondary radiation in the treatment room has been studied in function of the beam modulation. A strong correlation was found between the secondary ambient dose equivalent per proton dose H*(10)/D and proton dose rate D/MU. A large volume ionisation chamber fixed on the wall at 2.5 m from the nozzle was used with an in-house computer interface to retrieve the value of D/MU derived from the measurement of photon H*(10) integrated over treatment time, using the correlation curve. This system enables the verification of D and D/MU to be made independently of the monitoring of the primary beam and represents a first step towards an alternative in vivo dosimetry in proton therapy.

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.

Study of the secondary neutral radiation in proton therapy: toward an indirect in vivo dosimetry.

PURPOSE: Secondary particles produced in the collision of protons with beam modifiers are of concern in proton therapy. Nevertheless, secondary radiation can provide information on the dosimetric parameters through its dependency on the modulating accessories (range shifter and range modulating wheel). Relatively little data have been reported in the literature for low-energy proton beams. The present study aims at characterizing the neutron and photon secondary radiation at the low-energy proton therapy facility of the Centre Antoine Lacassagne (CAL), and studying their correlation to the dosimetric parameters to explore possible practical uses of secondary radiation in the treatment quality for proton therapy. METHODS: The Monte Carlo code MCNPX was used to simulate the proton therapy facility at CAL. Neutron and photon fluence, Φ, and ambient dose equivalent per proton dose, H∗(10)∕D, were determined across the horizontal main plane spanning the whole treatment room. H∗(10)∕D was also calculated at two positions of the treatment room where dosimetric measurements were performed for validation of the Monte Carlo calculations. Calculations and measurements were extended to 100 clinical spread-out Bragg Peaks (SOBPs) covering the whole range of therapeutic dose rates (D∕MU) employed at CAL. In addition, the values of D and MU were also calculated for each SOBP and the results analyzed to study the relationship between secondary radiation and dosimetric parameters. RESULTS: The largest production of the secondary particles takes place at the modulating devices and the brass collimators located along the optical bench. Along the beam line and off the beam axis to 2.5 m away, H∗(10)∕D values ranged from 5.4 µSv∕Gy to 5.3 mSv∕Gy for neutrons, and were 1 order of magnitude lower for photons. H∗(10)∕D varied greatly with the distance and angle to the beam axis. A variation of a factor of 5 was found for the different range of modulations (SOBPs). The ratios between calculations and measurements were 2.3 and 0.5 for neutrons and photons, respectively, and remained constant for all the range of SOBPs studied, which provided validation for the Monte Carlo calculations. H∗(10)∕D values were found to correlate to the proton dose rate D∕MU with a power fit, both for neutrons and photons. This result was exploited to implement a system to obtain D∕MU values from the measurement of the integrated photon ambient dose equivalent H∗(10) during treatment, which provides a method to control the dosimetric parameters D∕MU and D. CONCLUSIONS: The treatment room at CAL is moderately polluted by secondary particles. The constant ratio between measurements and calculations for all SOBPs showed that simulations correctly predict the dosimetric parameters and the dependence of the production of secondary particles on the modulation. The correlation between H∗(10)∕D and D∕MU is a useful tool for quality control and is currently used at CAL. This system works as an indirect in vivo dosimetry method, which is so far not feasible in proton therapy. This tool requires very simple instrumentation and can be implemented from the measurement of either photons or neutrons.

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.

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.

Extension of the calibration curve for the PGRA facility in Petten.

At the boron neutron capture therapy (BNCT) facility in Petten, the Netherlands, (10)B concentrations in biological materials are measured with the prompt gamma ray analyses facility that is calibrated using certified (10)B solutions ranging from 0 to 210 ppm. For this study, newly certified (10)B solutions ranging up to 1972 ppm are added. MCNP simulations of the setup range to 5000 ppm. A second order polynomial (as already used) will fit (10)B-concentrations less than 300 ppm. Above 300 ppm a fitted third order polynomial is needed to describe the calibration curve accurately.

Early clinical trial concept for boron neutron capture therapy: a critical assessment of the EORTC trial 11001.

BNCT causes selective damage to tumor cells by neutron capture reactions releasing high LET-particles where (10)B-atoms are present. Neither the (10)B-compound nor thermal neutrons alone have any therapeutic effect. Therefore, the development of BNCT to a treatment modality needs strategies, which differ from the standard phase I-III clinical trials. An innovative trial design was developed including translational research and a phase I aspect. The trial investigates as surrogate endpoint BSH and BPA uptake in different tumor entities.

Validation of a pencil beam model-based treatment planning system for fast neutron therapy.

Treatment planning systems (TPSs) are used to compute dose delivered to the patient. In the case of fast neutron therapy, TPSs are mostly not of general purpose but are dedicated to one facility. This is due to the few fast neutron facilities worldwide and due to the high variation in the neutron energy distributions. Efforts have been undertaken to develop a new TPS that could be applied to all the existing fast neutron facilities. The University Hospital of Essen operates a d (14 MeV) + Be fast neutron beam and the TPS used is based on an empirical model. In a previous study, the empirical model has been evolved to a pencil beam model of 35 monoenergetic neutron beams. Monte Carlo techniques have been utilized to compute distributions of the energy deposition due to primary and scattered neutrons in a simple geometry water phantom. The experimental validation of the method is now presented. Depth dose curves in water of monoenergetic neutrons have been derived from the distributions of energy deposition. The resultant depth dose curves have been utilized in order to determine the depth dose curves of the fast neutron beam of the Essen facility for the 14 radiation field sizes available in this facility. This determination requires the initial neutron spectrum. As this spectrum could not be measured at the Essen facility, the initial neutron spectrum of the Physikalisch Technische Bundesanstalt, Braunschweig, Germany, which operates the same cyclotron, was used. The calculated depth dose curves were compared to experimental depth dose curves that have been obtained in water at the University Hospital of Essen. The comparison between calculated and experimental depth dose curves showed significant deviations in the case of large radiation fields and of depth less than 5 cm. In the case of radiation field areas less than 150 cm2 and depth more than 5 cm (usual clinical situation), the measured and calculated values are in a good agreement. In the case of clinical situation, the dependence on the radiation field size is relatively well taken into account by the model presented here.

Empirical description and Monte Carlo simulation of fast neutron pencil beams as basis of a treatment planning system.

The fast neutron beam, used for fast neutron therapy in Essen, is produced by the nuclear reaction of a 14 MeV cyclotron-based deuteron beam on a thick beryllium target. The resulting neutron beam has a continuous energy spectrum with a mean and a maximum energy equal to 5.5 and 18 MeV, respectively. The dose delivered to the patient is computed by a treatment planning system (TPS) based on an empirical model, in which the dose components (neutron and photon) are described by analytical functions. In order to improve the dose calculation, and thus to use the fast neutron beam for other applications (e.g., Boron Neutron Capture Enhancement of Fast Neutron Therapy), in this work we aim to develop a new TPS. For this purpose, a model based on pencil beams of mono-energetic neutrons has been created. The neutron energy ranged from 0.25 MeV up to 17.25 MeV by steps of 0.5 MeV in order to cover the energy range of the Essen facility. The Monte Carlo method was then used to simulate the transport of neutrons within such pencil beams in a homogeneous water phantom. By using Monte Carlo techniques, it is possible to distinguish the energy deposition due to a primary collision in water to that due to scattered neutrons. The energy deposition due to pencil beams of 2.224 MeV photons, coming from hydrogen neutron capture reaction in the phantom or in the collimator, was also determined. In order to complete this work, air filled cylinders have been introduced in the water phantom. It is shown that the resulting depth dose curves for primary neutrons can be easily derived using the homogeneous phantom, and that the description of the effect on scattered neutron dose distribution is more complex. In this work we demonstrate the relevance of Monte Carlo simulations of mono-energetic neutron pencil beams for purposes of neutron treatment planning. Some additional work is still required to describe a clinical situation (continuous energy neutron spectrum) as well as to experimentally validate the method described here.

Towards in vivo monitoring of neutron distributions for quality control of BNCT.

Dose delivery in boron neutron capture therapy (BNCT) is complex because several components contribute to the dose absorbed in tissue. This dose is largely determined by local boron concentration, thermal neutron distribution and patient positioning. In vivo measurements of these factors would considerably improve quality control and safety. During therapy, a y-ray telescope measures the y-rays emitted following neutron capture by hydrogen and boron in a small volume of the head of a patient. Scans of hydrogen y-ray emissions could be used to verify the actual distribution of thermal neutrons during neutron irradiation. The method was first tested on different phantoms. These measurements showed good agreement with calculations based on thermal neutron distributions derived from a treatment planning program and from Monte Carlo N-particle (MCNP) simulations. Next, the feasibility of telescope scans during patient irradiation therapy was demonstrated. Measurements were reproducible between irradiation fractions. In theory, this method can be used to verify the positioning of the patient in vivo and the delivery of thermal neutrons in tissue. However, differences between measurements and calculations based on a routine treatment planning program were observed. These differences could be used to refine the treatment planning. Further developments will be necessary for this method to become a standard quality control system.

Calculation of boron neutron capture cell inactivation in vitro based on particle track structure and x-ray sensitivity.

The Monte-Carlo technique was used to perform quantitative microdosimetric model calculations of cell survival after boron neutron capture irradiations in vitro. The high energy 7Li and alpha-particles resulting from the neutron capture reaction 10B (n,alpha)7Li are of short range and are highly damaging to cells. The biophysical model of the Monte-Carlo calculations is based on the track structure of these a-particles and 7Li-ions and the x-ray sensitivity of the irradiated cells. The biological effect of these particles can be determined if the lethal effect of local doses deposited in very small fractional volumes of the cell nucleus is known. This lethal effect can be deduced from experimental data of cell survival after x-ray irradiation assuming a Poisson distribution for lethal events. The input data used in a PC-based computer program are the radial dose distribution inside the track of the released particles, cell survival after x-ray irradiation, geometry of the tumor cells, subcellular 10B concentration, and thermal neutron fluence. The basic concept of this Monte-Carlo computer model is demonstrated. Validations of computer calculations are presented by comparing them with experimental data on cell survival.

Assessment of local recurrence after breast-conserving therapy with MRI.

PURPOSE: The purpose of our study was to evaluate the relevance of MR mammography in the diagnosis of early and late tumor recurrence after breast-conserving therapy. METHOD: Sixty-seven patients receiving breast-conserving therapy underwent 84 MR mammographies in a period between 1 month and 14 years after end of therapy. Dynamic measurements were made following application of contrast agent. The course of signal intensity changes was evaluated in focal lesions and irradiated and contralateral glandular tissue. RESULTS: All 10 malignant lesions (7 local recurrences, 1 chest wall recurrence, 2 contralateral carcinomas) showed a > 75% increase in signal intensity within th first minute after contrast agent application. In all patients examined during the first year after end of therapy (n = 29), increased enhancement in irradiated parenchyma was observed compared with the contralateral breast, but only in two patients the increase was > 75% within the first minute. CONCLUSION: Already in the first year after end of therapy, MRI can improve diagnostic accuracy in the assessment of breast cancer recurrence. More than 12 months following end of therapy, MR mammography can demonstrate tumor recurrence with a sensitivity of nearly 100% and a specificity rising to > 90% in differentiating tumor from therapy-induced changes.

Monte Carlo simulation of the biological effects of boron neutron capture irradiation with d(14)+Be neutrons in vitro.

It was shown that radiation effects in tumor cells treated with fast neutrons may be increased by the neutron capture reaction 10B(n, alpha)7Li. The classic approach for macroscopic dosimetry in fast-neutron therapy cannot be applied to the dose in boron neutron capture therapy (BNCT). The effectiveness of BNCT in killing tumor cells depends on the number of 10B atoms delivered to the tumor, the subcellular distribution of 10B and the thermal neutron fluence at the site of the tumor. Monte Carlo calculations of the energy depositions of short-range particles with high LET coming from 10B disintegrations were performed and compared to the observed biological effects. The simulation allows us to study the influence of the localization of intracellular 10B in the nucleus, cytoplasma, plasma membrane or extracellular space. The biological response function which describes the probability of the lethal effect produced by a single particle track through the cell nucleus was found by comparing the calculated microscopic dose distribution spectra for single events with the survival observed experimentally. Calculations for a human melanoma cell population treated as a monolayer in the presence or absence of boron with d(14)+Be neutrons will be demonstrated. Two different boron compounds enriched in 10B were investigated in this study: boric acid (H3 10BO3) and p-dihydroxyboryl phenylalanine (BPA). The study shows that a high fraction of BPA enters the cytoplasm while boric acid was found only in the extracellular space. The computer simulations indicate that BPA yields a higher potential effectiveness for inactivation of melanoma cells than boric acid.

Monte Carlo calculation of dose enhancement by neutron capture of 10B in fast neutron therapy.

Since 1978 the Essen Medical Cyclotron Facility has been used for fast neutron therapy. The treatment of deep-seated tumours by d(14) + Be neutron beam therapy (mean energy = 5.8 MeV) is still limited because of the steep decrease in depth-dose distribution. The interactions of fast neutrons in tissue leads to a thermal neutron distribution. These partially thermalized neutrons can be used to produce neutron capture reactions with 10B. Thus incorporation of 10B in tumours treated with fast neutrons will increase the relative local tumour dose due to the reaction 10B (n, alpha) 7Li. The magnitude of dose enhancement by 10B depends on the distribution of the thermal neutron fluence, 10B concentration, field size of the neutron beam, beam energy and the specific phantom geometry. The slowing down of the fast neutrons, resulting in a thermal neutron distribution in a phantom, has been computed using a Monte Carlo model. This model, which includes a deep-seated tumour, was experimentally verified by measurements of the thermal neutron fluence rate in a phantom using neutron activation of gold foil. When non-boronated water phantoms were irradiated with a total dose of 1 Gy at a depth of 6 cm, the thermal fluencies at this depth were found to be 2 x 10(10) cm-2. The absorbed dose in a tumour with 100 ppm 10B, at the same depth, was enhanced by 15%.