Effect of chronic hypoxia on RAGE and its soluble forms in lungs and plasma of mice.

The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor. Alternative splicing and enzymatic shedding produce soluble forms that protect against damage by ligands including Advanced Glycation End products (AGEs). A link between RAGE and oxygen levels is evident from studies showing RAGE-mediated injury following hyperoxia. The effect of hypoxia on pulmonary RAGE expression and circulating sRAGE levels is however unknown. Therefore mice were exposed to chronic hypoxia for 21 d and expression of RAGE, sheddases in lungs and circulating sRAGE were determined. In addition, accumulation of AGEs in lungs and expression of the AGE detoxifying enzyme GLO1 and receptors were evaluated. In lung tissue gene expression of total RAGE, variants 1 and 3 were elevated in mice exposed to hypoxia, whereas mRAGE and sRAGE protein levels were decreased. In the hypoxic group plasma sRAGE levels were enhanced. Although the levels of pro-ADAM10 were elevated in lungs of hypoxia exposed mice, the relative amount of the active form was decreased and gelatinase activity unaffected. In the lungs, the RAGE ligand HMGB1 was decreased and of the AGEs, only LW-1 was increased by chronic hypoxia. Gene expression of AGE receptors 2 and 3 was significantly upregulated. Chronic hypoxia is associated with downregulation of pulmonary RAGE protein levels, but a relative increase in sRAGE. These alterations might be part of the adaptive and protective response mechanism to chronic hypoxia and are not associated with AGE formation except for the fluorophore LW-1 which emerges as a novel marker of tissue hypoxia.

Integration of the M6 Cyberknife in the Moderato Monte Carlo platform and prediction of beam parameters using machine learning.

PURPOSE: This work describes the integration of the M6 Cyberknife in the Moderato Monte Carlo platform, and introduces a machine learning method to accelerate the modelling of a linac. METHODS: The MLC-equipped M6 Cyberknife was modelled and integrated in Moderato, our in-house platform offering independent verification of radiotherapy dose distributions. The model was validated by comparing TPS dose distributions with Moderato and by film measurements. Using this model, a machine learning algorithm was trained to find electron beam parameters for other M6 devices, by simulating dose curves with varying spot size and energy. The algorithm was optimized using cross-validation and tested with measurements from other institutions equipped with a M6 Cyberknife. RESULTS: Optimal agreement in the Monte Carlo model was reached for a monoenergetic electron beam of 6.75 MeV with Gaussian spatial distribution of 2.4 mm FWHM. Clinical plan dose distributions from Moderato agreed within 2% with the TPS, and film measurements confirmed the accuracy of the model. Cross-validation of the prediction algorithm produced mean absolute errors of 0.1 MeV and 0.3 mm for beam energy and spot size respectively. Prediction-based simulated dose curves for other centres agreed within 3% with measurements, except for one device where differences up to 6% were detected. CONCLUSIONS: The M6 Cyberknife was integrated in Moderato and validated through dose re-calculations and film measurements. The prediction algorithm was successfully applied to obtain electron beam parameters for other M6 devices. This method would prove useful to speed up modelling of new machines in Monte Carlo systems.

Monte Carlo dose calculations of shielding disks with different material combinations in intraoperative electron radiation therapy (IOERT).

PURPOSE: Shielding disks play an important role in intraoperative electron radiation therapy, and different designs are currently used in clinical practice. This paper investigates the dosimetric impact of the shielding disk used during intraoperative electron radiation therapy (IOERT). MATERIALS AND METHODS: This paper focuses on the study of four shielding disks types that have been used in our clinic: Aluminum (Al)/Lead (Pb), PMMA/Copper(Cu)/PMMA, Aluminum (Al)/Copper (Cu) and Aluminum (Al)/Steel with their specific thicknesses. The theoretical study was conducted with the EGSnrc Monte Carlo (MC) code. On the other hand, the measurements were carried out with gafchromic films for the four shielding disks for the same setup inside the water phantom. Finally, a comparison of the simulated and measured PDD curves was performed for the four material combinations. RESULTS: MC simulation and gafchromic measurements illustrated that dose values under the four shielding disks types were close to 0, whereas the backscattering enhancement of the disks were 103% with Al/Pb shielding disk, 102% with Al/Steel shielding disk, 102% with Al/Cu shielding disk, 95% with PMMA/Cu/PMMA shielding disk. The PDDs values of the gafchromic films in front of the disks were: 107%, 105%, 104%, and 94% for the Al/Pb, Al/Steel, Al/Cu, and PMMA/Cu/PMMA disks respectively. CONCLUSIONS: The dose values above and under the shielding disks were acceptable for the four studied shielding types. Demonstrated it is possible to use any of them clinically, while the best shielding disk was the Al/Pb since it has minimum thickness and a small backscatter enhancement.

Head-and-Neck MRI-only radiotherapy treatment planning: From acquisition in treatment position to pseudo-CT generation.

PURPOSE: In context of head-and-neck radiotherapy, this study aims to compare MR image quality according to diagnostic (DIAG) and radiotherapy (RT) setups; and to optimise an MRI-protocol (including 3D T1 and T2-weighted sequences) for dose-planning (based on pseudo-CT generation). MATERIALS AND METHODS: To compare DIAG and RT setups, signal-to-noise-ratio (SNR) and percentage-image-uniformity (PIU) were computed on T1 images of phantoms and volunteers. Influence of the sample conductivity on SNR was quantified using homemade phantoms. To obtain reliable T1 and T2 images for RT-planning, an experimental design was performed on volunteers by using SNR, contrast-to-noise-ratio (CNR) and mean-opinion-score (MOS). Further, pseudo-CTs were generated from 8 patients T2 images with a state-of-art deep-learning method. These pseudo-CTs were evaluated by mean-absolute-error (MAE) and mean-error (ME). RESULTS: SNR was higher for DIAG-setup compared to RT-setup (SNR-ratio=1.3). A clear influence of the conductivity on SNR was observed. PIU was higher for DIAG-setup (38.8%) compared to RT-setup (33.5%). Regarding the protocol optimisation, SNR, CNR, and MOS were 20.6, 6.16, and 3.91 for the optimal T1 sequence. For the optimal T2 sequence, SNR, CNR and MOS were 25.6, 44.46 and 4.0. In the whole head-and-neck area, the mean MAE and ME of the pseudo-CTs were 82.8 and -3.9 HU. CONCLUSION: We quantified the image quality decrease induces by using an RT-setup for head-and-neck radiotherapy. To compensate this decrease, an MRI protocol was optimised by using an experimental design. This protocol of 15minutes provides accurate images which could be used for MRI-dose-planning in clinical practice.

The influence of small field sizes, penumbra, spot size and measurement depth on perturbation factors for microionization chambers.

The purpose of this study was the investigation of perturbation factors for microionization chambers in small field dosimetry and the influence of penumbra for different spot sizes. To this purpose, correlated sampling was implemented in the EGSnrc Monte Carlo (MC) user code cavity: CScavity. CScavity was first benchmarked against results in the literature for an NE2571 chamber. An efficiency increase of 17 was attained for the calculation of a realistic chamber perturbation factor in a water phantom. Calculations have been performed for microionization chambers of type PinPoint 31006 and PinPoint 31016 in full BEAMnrc linac simulations. Investigating the physical backgrounds of the differences for these small field settings, perturbation factors have been split up into (1) central electrode perturbation, (2) wall perturbation, (3) air-to-water perturbation (chamber volume air-to-water) and (4) water volume perturbation (water chamber volume to 1 mm(3) voxel). The influence of different spot sizes, position in penumbra, measuring depth and detector geometry on these perturbation factors has been investigated, in a 0.8 x 0.8 cm(2) field setting. p(cel) for the PP31006 steel electrode shows a variation of up to 1% in the lateral position, but only 0.4% for the PP31016 with an Al electrode. The air-to-water perturbation in the optimal scanning direction for both profiles and depth is most influenced by the radiation field, and only to a small extent the chamber geometry. The PP31016 geometry (shorter, larger radius) requires less total perturbation within the central axis of the field, but results in slightly larger variations off axis in the optimal scanning direction. Smaller spot sizes (0.6 mm FWHM) and sharper penumbras, compared to larger spot sizes (2 mm FWHM), result in larger perturbation starting in the penumbra. The longer geometries of the PP31006/14/15 exhibit in the non-optimal scanning direction large variations in total perturbation (p(tot) 1.201(4) (0.6 mm spot, 3 mm off axis, type A MC uncertainty) to 0.803(4) (5 mm off axis)) mainly due to volume perturbation. Therefore in IMRT settings, when the detector is not always in the optimal scanning direction, the PP31016 geometry requires less extreme perturbation (max p(tot) 1.130(3)) and shows less variation. However, these results suggest that small variations in positioning, spot size or MLC result in large differences in perturbation factors. Therefore even these 0.016 cm(3) ionization chambers are limited in their use for a field setting of 0.8 x 0.8 cm(2), as used in this investigation.

PET and MRI based RT treatment planning: Handling uncertainties.

Imaging provides the basis for radiotherapy. Multi-modality images are used for target delineation (primary tumor and nodes, boost volume) and organs at risk, treatment guidance, outcome prediction, and treatment assessment. Next to anatomical information, more and more functional imaging is being used. The current paper provides a brief overview of the different applications of imaging techniques used in the radiotherapy process, focusing on uncertainties and QA. The paper mainly focuses on PET and MRI, but also provides a short discussion on DCE-CT. A close collaboration between radiology, nuclear medicine and radiotherapy departments provides the key to improve the quality of radiotherapy. Jointly developed imaging protocols (RT position setup, immobilization tools, lasers, flat table…), and QA programs are mandatory. For PET, suitable windowing in consultation with a Nuclear Medicine Physician is crucial (differentiation benign/malignant lesions, artifacts…). A basic knowledge of MRI sequences is required, in such a way that geometrical distortions are easily recognized by all members the RT and RT physics team. If this is not the case, then the radiologist should be introduced systematically in the delineation process and multidisciplinary meetings need to be organized regularly. For each image modality and each image registration process, the associated uncertainties need to be determined and integrated in the PTV margin. When using functional information for dose painting, response assessment or outcome prediction, collaboration between the different departments is even more important. Limitations of imaging based biomarkers (specificity, sensitivity) should be known.

[Radiotherapy treatment planning of prostate cancer using magnetic resonance imaging]. / Planification de la radiothérapie du cancer de la prostate par l'imagerie par résonance magnétique.

PURPOSE: Magnetic resonance imaging (MRI) plays an increasing role in radiotherapy dose planning. Indeed, MRI offers superior soft tissue contrast compared to computerized tomography (CT) and therefore could provide a better delineation of target volumes and organs at risk than CT for radiotherapy. Furthermore, an MRI-only radiotherapy workflow would suppress registration errors inherent to the registration of MRI with CT. However, the estimation of the electronic density of tissues using MRI images is still a challenging issue. The purpose of this work was to design and evaluate a pseudo-CT generation method for prostate cancer treatments. MATERIALS AND METHODS: A pseudo-CT was generated for ten prostate cancer patients using an elastic deformation based method. For each patient, dose delivered to the patient was calculated using both the planning CT and the pseudo-CT. Dose differences between CT and pseudo-CT were investigated. RESULTS: Mean dose relative difference in the planning target volume is 0.9% on average and ranges from 0.1% to 1.7%. In organs at risks, this value is 1.8%, 0.8%, 0.8% and 1% on average in the rectum, the right and left femoral heads, and the bladder respectively. CONCLUSION: The dose calculated using the pseudo-CT is very close to the dose calculated using the CT for both organs at risk and PTV. These results confirm that pseudo-CT images generated using the proposed method could be used to calculate radiotherapy treatment doses on MRI images.

Adult Height after Growth Hormone Treatment at Pubertal Onset in Short Adolescents Born Small for Gestational Age: Results from a Belgian Registry-Based Study.

OBJECTIVES: Information on the efficacy of GH treatment in short SGA children starting their treatment in adolescence is limited. Therefore, adult height (AH), total height gain, and pubertal height gain were evaluated in short SGA children who started GH treatment at pubertal onset. PATIENT AND METHODS: Growth data of 47 short SGA adolescents (22 boys) who started GH treatment at pubertal onset (PUB group) were compared with results from 27 short SGA patients (11 boys) who started GH therapy at least 1 year before pubertal onset (PrePUB group). RESULTS: The PUB group achieved a mean (±SD) total height gain of 0.8 ± 0.7 SDS and an AH of -2.5 ± 0.7 SDS after 4.1 ± 1.1 years of GH treatment with a dosage of 41.8 ± 8.4 µg/kg/day. These results were comparable with those in the PrePUB group, which was treated for a longer duration (5.8 ± 2.1 years), resulting in a total height gain of 1.1 ± 0.7 SDS and an AH of -2.1 ± 1.0 SDS. Multiple regression analysis showed a significantly lower height gain in pubertal patients, females, and patients weighing less at start of GH treatment. An AH above -2 SDS and above the parent-specific lower limit of height was, respectively, reached in 28% and 70% of PUB and 44% and 67% of PrePUB patients (NS). AH SDS was positively correlated with the height SDS at start of GH. CONCLUSIONS: Short SGA adolescents starting GH therapy at an early pubertal stage have a modest and variable height gain. A normal AH can be expected in one third of the patients, especially in those with a smaller height deficit at onset of GH treatment.

Monte carlo evaluation of the AAA treatment planning algorithm in a heterogeneous multilayer phantom and IMRT clinical treatments for an Elekta SL25 linear accelerator.

The Anisotropic Analytical Algorithm (AAA) is a new pencil beam convolution/superposition algorithm proposed by Varian for photon dose calculations. The configuration of AAA depends on linear accelerator design and specifications. The purpose of this study was to investigate the accuracy of AAA for an Elekta SL25 linear accelerator for small fields and intensity modulated radiation therapy (IMRT) treatments in inhomogeneous media. The accuracy of AAA was evaluated in two studies. First, AAA was compared both with Monte Carlo (MC) and the measurements in an inhomogeneous phantom simulating lung equivalent tissues and bone ribs. The algorithm was tested under lateral electronic disequilibrium conditions, using small fields (2 x 2 cm(2)). Good agreement was generally achieved for depth dose and profiles, with deviations generally below 3% in lung inhomogeneities and below 5% at interfaces. However, the effects of attenuation and scattering close to the bone ribs were not fully taken into account by AAA, and small inhomogeneities may lead to planning errors. Second, AAA and MC were compared for IMRT plans in clinical conditions, i.e., dose calculations in a computed tomography scan of a patient. One ethmoid tumor, one orophaxynx and two lung tumors are presented in this paper. Small differences were found between the dose volume histograms. For instance, a 1.7% difference for the mean planning target volume dose was obtained for the ethmoid case. Since better agreement was achieved for the same plans but in homogeneous conditions, these differences must be attributed to the handling of inhomogeneities by AAA. Therefore, inherent assumptions of the algorithm, principally the assumption of independent depth and lateral directions in the scaling of the kernels, were slightly influencing AAA's validity in inhomogeneities. However, AAA showed a good accuracy overall and a great ability to handle small fields in inhomogeneous media compared to other pencil beam convolution algorithms.

Monte Carlo modeling of the ModuLeaf miniature MLC for small field dosimetry and quality assurance of the clinical treatment planning system.

The purpose of this investigation was the verification of both the measured data and quality of the implementation of the add-on ModuLeaf miniature multileaf collimator (ML mMLC) into the clinical treatment planning system for conformal stereotactic radiosurgery treatment. To this end the treatment head with ML mMLC was modeled in the BEAMnrc Monte Carlo (MC) code. The 6 MV photon beams used in the setup were first benchmarked with a set of measurements. A total ML mMLC transmission of 1.13% of the 10 x 10 cm2 open field dose was measured and reproduced with the BEAMnrc/DOSXYZnrc code. Correspondence between calculated and measured output factors (OFs) was within 2%. Correspondence between MC and measured profiles was within 2% dose and 2 mm distance, only for the smallest 0.5 x 0.5 cm2 field the results were within 3% dose. In the next step, the MC model was compared with Gafchromic film measurements and Pinnacle(3) 7.4 f (convolution superposition algorithm) calculated dose distributions, using a gamma evaluation comparison, for a multi-beam patient setup delivered to a Lucytrade mark phantom. The gamma evaluation of the MC versus Gafchromic film resulted in 3.4% of points not fulfilling gamma

Use of an in-house Monte Carlo platform to assess the clinical impact of algorithm-related dose differences on DVH constraints.

PURPOSE: The aim of the present work is to evaluate a semi-automatic prescription and validation system of treatment plans for complex delivery techniques, integrated in a Monte Carlo platform, and to investigate the clinical impact of dose differences due to the calculation algorithms, by assessing the changes in DVH constraints. METHODS: A new prescription module was implemented into the Moderato system, an in-house Monte Carlo platform, with corresponding dose constraints generated depending on the anatomical region and fractionation scheme considered. The platform was tested on 83 cases treated with Cyberknife and Tomotherapy machines, to assess whether dose variations between the re-calculated dose and the Treatment Planning System might impact the dose constraints on the sensitive structures. RESULTS: Dose differences were small (within 3%) between calculation algorithms in most of the thoracic, pelvic and abdominal cases, both for the Cyberknife and Tomotherapy machines. On the other hand, spinal and head and neck treatments presented a few significant dose deviations for constraints on small volumes, such as the optic pathways and the spinal cord. These differences range from -11% to +6%, inducing constraint violations of up to 8% over the dose limit. CONCLUSIONS: The Moderato platform offers an interesting tool for plan quality validation, with a prescription module highlighting crucial features in the structures list, and a Monte Carlo dose re-calculation for complex modern techniques. Due to the high number of warnings appearing in some situations, display optimization is required in practice.

About the non-consistency of PTV-based prescription in lung.

PURPOSE: The goal of this study is to show that the PTV concept is inconsistent for prescribing lung treatments when using type B algorithms, which take into account lateral electron transport. It is well known that type A dose calculation algorithms are not capable of calculating dose in lung correctly. Dose calculations should be based on type B algorithms. However, the combination of a type B algorithm with the PTV concept leads to prescription inconsistencies. METHODS: A spherical isocentric setup has been simulated, using multiple realistic values for lung density, tumor density and collimator size. Different prescription methods are investigated using Dose-Volume-Histograms (DVH), Dose-Mass-Histograms (DMH), generalized Equivalent Uniform Dose (gEUD) and surrounding isodose percentage. RESULTS: Isodose percentages on the PTV drop down to 50% for small tumors and low lung density. When applying the same PTV prescription to different patients with different lung characteristics, the effective mean dose to the GTV is very different, with factors up to 1.4. The most consistent prescription method seems to be the D50%DMH (PTV) DMH point, but is also limited to tumors with size over 1cm. CONCLUSIONS: Even when using the different prescription methods, the prescription to the PTV is not consistent for type B-algorithm based dose calculations if clinical studies should produce coherent data. This combination leads to patients' GTV with low lung density possibly receiving very high dose compared to patients with higher lung density. The only solution seems to remove the classical PTV concept for type B dose calculations in lung.

Zero echo time MRI-only treatment planning for radiation therapy of brain tumors after resection.

Using magnetic resonance imaging (MRI) as the sole imaging modality for patient modeling in radiation therapy (RT) is a challenging task due to the need to derive electron density information from MRI and construct a so-called pseudo-computed tomography (pCT) image. We have previously published a new method to derive pCT images from head T1-weighted (T1-w) MR images using a single-atlas propagation scheme followed by a post hoc correction of the mapped CT numbers using local intensity information. The purpose of this study was to investigate the performance of our method with head zero echo time (ZTE) MR images. To evaluate results, the mean absolute error in bins of 20 HU was calculated with respect to the true planning CT scan of the patient. We demonstrated that applying our method using ZTE MR images instead of T1-w improved the correctness of the pCT in case of bone resection surgery prior to RT (that is, an example of large anatomical difference between the atlas and the patient).

Increased levels of enzymes involved in local estradiol synthesis in chronic obstructive pulmonary disease.

INTRODUCTION: Steroid hormones are involved in lung development, pulmonary inflammation, and lung cancer. Estrogen signaling and exposure may play a role in pulmonary disorders, including COPD. In both genders, estrogens can be generated locally in the lungs and this contributes importantly to the tissue exposure to these steroids. OBJECTIVE: To characterize and assess differences in localization of estrogen receptors and enzymes involved in the local generation of estrogens in COPD. METHODS: Estrogen Receptor alpha (ERα/ESR1), Estrogen Receptor beta (ERß/ESR2) and G-protein-coupled estrogen receptor 1 (GPER) were explored by real-time (RT)-PCR analysis (mRNA expression), immunohistochemistry and western blotting in controls and COPD patients. mRNA expression of the enzymes involved in the local estrogen generation - i.e. aromatase (CYP19A1), 17beta-hydroxysteroid dehydrogenases (17ß-HSDs) 1, 2, 4, 5, 7 and 12, steroid sulfatase (STS) and sulfotransferase (SULT1E1) - were analyzed by RT-PCR. RESULTS: ERα, ERß and GPER were expressed in lung tissue, but no differences were observed between patients and controls. The main enzymes involved in local estrogen generation were also present in both normal and COPD lung tissue. In lungs of COPD patients compared with controls, we observed increased expression of the enzymes 17ß-HSD type 1 and aromatase (positive association), both involved in the local synthesis of active estrogens. CONCLUSION: All ER subtypes are present in the lung. The shift in local mRNA level of estrogen metabolic enzymes suggests that exposure to estrogens is involved in the pathogenesis of COPD.

Denoising of Monte Carlo dose calculations: smoothing capabilities versus introduction of systematic bias.

In order to evaluate the performance of denoising algorithms applied to Monte Carlo calculated dose distributions, conventional evaluation methods (rms difference, 1% and 2% difference) can be used. However, it is illustrated that these evaluation methods sometimes underestimate the introduction of bias, since possible bias effects are averaged out over the complete dose distribution. In the present work, a new evaluation method is introduced based on a sliding window superimposed on a difference dose distribution (reference dose-noisy/denoised dose). To illustrate its importance, a new denoising technique (ANRT) is presented based upon a combination of the principles of bilateral filtering and Savitzky-Golay filters. This technique is very conservative in order to limit the introduction of bias in high dose gradient regions. ANRT is compared with IRON for three challenging cases, namely an electron and photon beam impinging on heterogeneous phantoms and two IMRT treatment plans of head-and-neck cancer patients to determine the clinical relevance of the obtained results. For the electron beam case, IRON outperforms ANRT concerning the smoothing capabilities, while no differences in systematic bias are observed. However, for the photon beam case, although ANRT and IRON perform equally well on the conventional evaluation tests (rms difference, 1% and 2% difference), IRON clearly introduces much more bias in the penumbral regions while ANRT seems to introduce no bias at all. When applied to the IMRT patient cases, both denoising methods perform equally well regarding smoothing and bias introduction. This is probably caused by the summation of a large set of different beam segments, decreasing dose gradients compared to a single beam. A reduction in calculation time without introducing large systematic bias can shorten a Monte Carlo treatment planning process considerably and is therefore very useful for the initial trial and error phase of the treatment planning process.

Clinical implementation of a Monte Carlo based treatment plan QA platform for validation of Cyberknife and Tomotherapy treatments.

PURPOSE: The main focus of the current paper is the clinical implementation of a Monte Carlo based platform for treatment plan validation for Tomotherapy and Cyberknife, without adding additional tasks to the dosimetry department. METHODS: The Monte Carlo platform consists of C++ classes for the actual functionality and a web based GUI that allows accessing the system using a web browser. Calculations are based on BEAMnrc/DOSXYZnrc and/or GATE and are performed automatically after exporting the dicom data from the treatment planning system. For Cyberknife treatments of moving targets, the log files saved during the treatment (position of robot, internal fiducials and external markers) can be used in combination with the 4D planning CT to reconstruct the actually delivered dose. The Monte Carlo platform is also used for calculation on MRI images, using pseudo-CT conversion. RESULTS: For Tomotherapy treatments we obtain an excellent agreement (within 2%) for almost all cases. However, we have been able to detect a problem regarding the CT Hounsfield units definition of the Toshiba Large Bore CT when using a large reconstruction diameter. For Cyberknife treatments we obtain an excellent agreement with the Monte Carlo algorithm of the treatment planning system. For some extreme cases, when treating small lung lesions in low density lung tissue, small differences are obtained due to the different cut-off energy of the secondary electrons. CONCLUSIONS: A Monte Carlo based treatment plan validation tool has successfully been implemented in clinical routine and is used to systematically validate all Cyberknife and Tomotherapy plans.

Investigation of geometrical and scoring grid resolution for Monte Carlo dose calculations for IMRT.

Monte Carlo based treatment planning of two different patient groups treated with step-and-shoot IMRT (head-and-neck and lung treatments) with different CT resolutions and scoring methods is performed to determine the effect of geometrical and scoring voxel sizes on DVHs and calculation times. Dose scoring is performed in two different ways: directly into geometrical voxels (or in a number of grouped geometrical voxels) or into scoring voxels defined by a separate scoring grid superimposed on the geometrical grid. For the head-and-neck cancer patients, more than 2% difference is noted in the right optical nerve when using voxel dimensions of 4 x 4 x 4 mm3 compared to the reference calculation with 1 x 1 x 2 mm3 voxel dimensions. For the lung cancer patients, 2% difference is noted in the spinal cord when using voxel dimensions of 4 x 4 x 10 mm3 compared to the 1 x 1 x 5 mm3 calculation. An independent scoring grid introduces several advantages. In cases where a relatively high geometrical resolution is required and where the scoring resolution is less important, the number of scoring voxels can be limited while maintaining a high geometrical resolution. This can be achieved either by grouping several geometrical voxels together into scoring voxels or by superimposing a separate scoring grid of spherical voxels with a user-defined radius on the geometrical grid. For the studied lung cancer cases, both methods produce accurate results and introduce a speed increase by a factor of 10-36. In cases where a low geometrical resolution is allowed, but where a high scoring resolution is required, superimposing a separate scoring grid on the geometrical grid allows a reduction in geometrical voxels while maintaining a high scoring resolution. For the studied head-and-neck cancer cases, calculations performed with a geometrical resolution of 2 x 2 x 2 mm3 and a separate scoring grid containing spherical scoring voxels with a radius of 2 mm produce accurate results and introduce a speed increase by a factor of 13. The scoring grid provides an additional degree of freedom for limiting calculation time and memory requirements by selecting optimized scoring and geometrical voxel dimensions in an independent way.

Experimental verification of lung dose with radiochromic film: comparison with Monte Carlo simulations and commercially available treatment planning systems.

The purpose of this study was to assess the absorbed dose in and around lung tissue by performing radiochromic film measurements, Monte Carlo simulations and calculations with superposition convolution algorithms. We considered a layered polystyrene phantom of 12 x 12 x 12 cm3 containing a central cavity of 6 x 6 x 6 cm3 filled with Gammex RMI lung-equivalent material. Two field configurations were investigated, a small 1 x 10 cm2 field and a larger 10 x 10 cm2 field. First, we performed Monte Carlo simulations to investigate the influence of radiochromic film itself on the measured dose distribution when the film intersects a lung-equivalent region and is oriented parallel to the central beam axis. To that end, the film and the lung-equivalent materials were modelled in detail, taking into account their specific composition. Next, measurements were performed with the film oriented both parallel and perpendicular to the central beam axis to verify the results of our Monte Carlo simulations. Finally, we digitized the phantom in two commercially available treatment planning systems, Helax-TMS version 6.1A and Pinnacle version 6.2b, and calculated the absorbed dose in the phantom with their incorporated superposition convolution algorithms to compare with the Monte Carlo simulations. Comparing Monte Carlo simulations with measurements reveals that radiochromic film is a reliable dosimeter in and around lung-equivalent regions when the film is positioned perpendicular to the central beam axis. Radiochromic film is also able to predict the absorbed dose accurately when the film is positioned parallel to the central beam axis through the lung-equivalent region. However, attention must be paid when the film is not positioned along the central beam axis, in which case the film gradually attenuates the beam and decreases the dose measured behind the cavity. This underdosage disappears by offsetting the film a few centimetres. We find deviations of about 3.6% between Monte Carlo and the superposition convolution algorithm of Pinnacle behind the lung region, for both field configurations. Pinnacle is quite accurate in the lung region. Deviations up to 5.6% for the small field are found in the lung region between Monte Carlo and the superposition convolution algorithm of Helax-TMS. Behind the lung region, Helax-TMS is in better agreement with Monte Carlo. Radiochromic film measurements or Monte Carlo simulations are reliable methods to establish the dose in and around lung tissue.

The importance of accurate linear accelerator head modelling for IMRT Monte Carlo calculations.

Two Monte Carlo dose engines for radiotherapy treatment planning, namely a beta release of Peregrine and MCDE (Monte Carlo dose engine), were compared with Helax-TMS (collapsed cone superposition convolution) for a head and neck patient for the Elekta SLi plus linear accelerator. Deviations between the beta release of Peregrine and MCDE up to 10% were obtained in the dose volume histogram of the optical chiasm. It was illustrated that the differences are not caused by the particle transport in the patient, but by the modelling of the Elekta SLi plus accelerator head and more specifically the multileaf collimator (MLC). In MCDE two MLC modules (MLCQ and MLCE) were introduced to study the influence of the tongue-and-groove geometry, leaf bank tilt and leakage on the actual dose volume histograms. Differences in integral dose in the optical chiasm up to 3% between the two modules have been obtained. For single small offset beams though the FWHM of lateral profiles obtained with MLCE can differ by more than 1.5 mm from profiles obtained with MLCQ. Therefore, and because the recent version of MLCE is as fast as MLCQ, we advise to use MLCE for modelling the Elekta MLC. Nevertheless there still remains a large difference (up to 10%) between Peregrine and MCDE. By studying small offset beams we have shown that the profiles obtained with Peregrine are shifted, too wide and too flat compared with MCDE and phantom measurements. The overestimated integral doses for small beam segments explain the deviations observed in the dose volume histograms. The Helax-TMS results are in better agreement with MCDE, although deviations exceeding 5% have been observed in the optical chiasm. Monte Carlo dose deviations of more than 10% as found with Peregrine are unacceptable as an influence on the clinical outcome is possible and as the purpose of Monte Carlo treatment planning is to obtain an accuracy of 2%. We would like to emphasize that only the Elekta MLC has been tested in this work, so it is certainly possible that alpha releases of Peregrine provide more accurate results for other accelerators.

Decoupling initial electron beam parameters for Monte Carlo photon beam modelling by removing beam-modifying filters from the beam path.

A new method is presented to decouple the parameters of the incident e(-) beam hitting the target of the linear accelerator, which consists essentially in optimizing the agreement between measurements and calculations when the difference filter, which is an additional filter inserted in the linac head to obtain uniform lateral dose-profile curves for the high energy photon beam, and flattening filter are removed from the beam path. This leads to lateral dose-profile curves, which depend only on the mean energy of the incident electron beam, since the effect of the radial intensity distribution of the incident e- beam is negligible when both filters are absent. The location of the primary collimator and the thickness and density of the target are not considered as adjustable parameters, since a satisfactory working Monte Carlo model is obtained for the low energy photon beam (6 MV) of the linac using the same target and primary collimator. This method was applied to conclude that the mean energy of the incident e- beam for the high energy photon beam (18 MV) of our Elekta SLi Plus linac is equal to 14.9 MeV. After optimizing the mean energy, the modelling of the filters, in accordance with the information provided by the manufacturer, can be verified by positioning only one filter in the linac head while the other is removed. It is also demonstrated that the parameter setting for Bremsstrahlung angular sampling in BEAMnrc ('Simple' using the leading term of the Koch and Motz equation or 'KM' using the full equation) leads to different dose-profile curves for the same incident electron energy for the studied 18 MV beam. It is therefore important to perform the calculations in 'KM' mode. Note that both filters are not physically removed from the linac head. All filters remain present in the linac head and are only rotated out of the beam. This makes the described method applicable for practical usage since no recommissioning process is required.