Statistical distribution of depth-integrated local horizontal momentum for second-order random ocean waves in finite water depth

Based on the second-order random wave solutions of water wave equations in finite water depth, statistical distributions of the depth- integrated local horizontal momentum components are derived by use of the characteristic function expansion method. The parameters involved in the distributions can be all determined by the water depth and the wave-number spectrum of ocean waves. As an illustrative example, a fully developed wind-generated sea is considered and the parameters are calculated for typical wind speeds and water depths by means of the Donelan and Pierson spectrum. The effects of nonlinearity and water depth on the distributions are also investigated.

Monte Carlo Analysis and Physics Characterization of a Novel Nanoparticle Detector for Medical and Micro-dosimetry Applications

The outcomes for both (i) radiation therapy and (ii) preclinical small animal radio- biology studies are dependent on the delivery of a known quantity of radiation to a specific and intentional location. Adverse effects can result from these procedures if the dose to the target is too high or low, and can also result from an incorrect spatial distribution in which nearby normal healthy tissue can be undesirably damaged by poor radiation delivery techniques. Thus, in mice and humans alike, the spatial dose distributions from radiation sources should be well characterized in terms of the absolute dose quantity, and with pin-point accuracy. When dealing with the steep spatial dose gradients consequential to either (i) high dose rate (HDR) brachytherapy or (ii) within the small organs and tissue inhomogeneities of mice, obtaining accurate and highly precise dose results can be very challenging, considering commercially available radiation detection tools, such as ion chambers, are often too large for in-vivo use.

In this dissertation two tools are developed and applied for both clinical and preclinical radiation measurement. The first tool is a novel radiation detector for acquiring physical measurements, fabricated from an inorganic nano-crystalline scintillator that has been fixed on an optical fiber terminus. This dosimeter allows for the measurement of point doses to sub-millimeter resolution, and has the ability to be placed in-vivo in humans and small animals. Real-time data is displayed to the user to provide instant quality assurance and dose-rate information. The second tool utilizes an open source Monte Carlo particle transport code, and was applied for small animal dosimetry studies to calculate organ doses and recommend new techniques of dose prescription in mice, as well as to characterize dose to the murine bone marrow compartment with micron-scale resolution.

Hardware design changes were implemented to reduce the overall fiber diameter to <0.9 mm for the nano-crystalline scintillator based fiber optic detector (NanoFOD) system. Lower limits of device sensitivity were found to be approximately 0.05 cGy/s. Herein, this detector was demonstrated to perform quality assurance of clinical 192Ir HDR brachytherapy procedures, providing comparable dose measurements as thermo-luminescent dosimeters and accuracy within 20% of the treatment planning software (TPS) for 27 treatments conducted, with an inter-quartile range ratio to the TPS dose value of (1.02-0.94=0.08). After removing contaminant signals (Cerenkov and diode background), calibration of the detector enabled accurate dose measurements for vaginal applicator brachytherapy procedures. For 192Ir use, energy response changed by a factor of 2.25 over the SDD values of 3 to 9 cm; however a cap made of 0.2 mm thickness silver reduced energy dependence to a factor of 1.25 over the same SDD range, but had the consequence of reducing overall sensitivity by 33%.

For preclinical measurements, dose accuracy of the NanoFOD was within 1.3% of MOSFET measured dose values in a cylindrical mouse phantom at 225 kV for x-ray irradiation at angles of 0, 90, 180, and 270˝. The NanoFOD exhibited small changes in angular sensitivity, with a coefficient of variation (COV) of 3.6% at 120 kV and 1% at 225 kV. When the NanoFOD was placed alongside a MOSFET in the liver of a sacrificed mouse and treatment was delivered at 225 kV with 0.3 mm Cu filter, the dose difference was only 1.09% with use of the 4x4 cm collimator, and -0.03% with no collimation. Additionally, the NanoFOD utilized a scintillator of 11 µm thickness to measure small x-ray fields for microbeam radiation therapy (MRT) applications, and achieved 2.7% dose accuracy of the microbeam peak in comparison to radiochromic film. Modest differences between the full-width at half maximum measured lateral dimension of the MRT system were observed between the NanoFOD (420 µm) and radiochromic film (320 µm), but these differences have been explained mostly as an artifact due to the geometry used and volumetric effects in the scintillator material. Characterization of the energy dependence for the yttrium-oxide based scintillator material was performed in the range of 40-320 kV (2 mm Al filtration), and the maximum device sensitivity was achieved at 100 kV. Tissue maximum ratio data measurements were carried out on a small animal x-ray irradiator system at 320 kV and demonstrated an average difference of 0.9% as compared to a MOSFET dosimeter in the range of 2.5 to 33 cm depth in tissue equivalent plastic blocks. Irradiation of the NanoFOD fiber and scintillator material on a 137Cs gamma irradiator to 1600 Gy did not produce any measurable change in light output, suggesting that the NanoFOD system may be re-used without the need for replacement or recalibration over its lifetime.

For small animal irradiator systems, researchers can deliver a given dose to a target organ by controlling exposure time. Currently, researchers calculate this exposure time by dividing the total dose that they wish to deliver by a single provided dose rate value. This method is independent of the target organ. Studies conducted here used Monte Carlo particle transport codes to justify a new method of dose prescription in mice, that considers organ specific doses. Monte Carlo simulations were performed in the Geant4 Application for Tomographic Emission (GATE) toolkit using a MOBY mouse whole-body phantom. The non-homogeneous phantom was comprised of 256x256x800 voxels of size 0.145x0.145x0.145 mm3. Differences of up to 20-30% in dose to soft-tissue target organs was demonstrated, and methods for alleviating these errors were suggested during whole body radiation of mice by utilizing organ specific and x-ray tube filter specific dose rates for all irradiations.

Monte Carlo analysis was used on 1 µm resolution CT images of a mouse femur and a mouse vertebra to calculate the dose gradients within the bone marrow (BM) compartment of mice based on different radiation beam qualities relevant to x-ray and isotope type irradiators. Results and findings indicated that soft x-ray beams (160 kV at 0.62 mm Cu HVL and 320 kV at 1 mm Cu HVL) lead to substantially higher dose to BM within close proximity to mineral bone (within about 60 µm) as compared to hard x-ray beams (320 kV at 4 mm Cu HVL) and isotope based gamma irradiators (137Cs). The average dose increases to the BM in the vertebra for these four aforementioned radiation beam qualities were found to be 31%, 17%, 8%, and 1%, respectively. Both in-vitro and in-vivo experimental studies confirmed these simulation results, demonstrating that the 320 kV, 1 mm Cu HVL beam caused statistically significant increased killing to the BM cells at 6 Gy dose levels in comparison to both the 320 kV, 4 mm Cu HVL and the 662 keV, 137Cs beams.

Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy.

The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential large block sections of whole prostatectomy specimens. Inverse planned IMRT dose distributions were created to irradiate the prostate to 70 Gy and all the IPTNs to 90 Gy. A second plan was produced to escalate only the dominant IPTN (DIPTN) to 90 Gy, mimicking current imaging techniques. These plans were compared with homogeneous prostate irradiation to 70 Gy using dose–volume histograms, tumour control probability (TCP) and normal tissue complication probability (NTCP) for the rectum. The mean dose to IPTNs was increased from 69.8 Gy to 89.1 Gy if all the IPTNs were dose escalated (p=0.0003). This corresponded to a mean increase in TCP of 8.7–31.2% depending on the /ß ratio of prostate cancer (p

Implications of Intercellular Signaling for Radiation Therapy: A Theoretical Dose-Planning Study

Purpose
Recent in vitro results have shown significant contributions to cell killing from signaling effects at doses that are typically used in radiation therapy. This study investigates whether these in vitro observations can be reconciled with in vivo knowledge and how signaling may have an impact on future developments in radiation therapy.
Methods and Materials
Prostate cancer treatment plans were generated for a series of 10 patients using 3-dimensional conformal therapy, intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy techniques. These plans were evaluated using mathematical models of survival following modulated radiation exposures that were developed from in vitro observations and incorporate the effects of intercellular signaling. The impact on dose-volume histograms and mean doses were evaluated by converting these survival levels into "signaling-adjusted doses" for comparison.
Results
Inclusion of intercellular communication leads to significant differences between the signalling-adjusted and physical doses across a large volume. Organs in low-dose regions near target volumes see the largest increases, with mean signaling-adjusted bladder doses increasing from 23 to 33 Gy in IMRT plans. By contrast, in high-dose regions, there is a small decrease in signaling-adjusted dose due to reduced contributions from neighboring cells, with planning target volume mean doses falling from 74 to 71 Gy in IMRT. Overall, however, the dose distributions remain broadly similar, and comparisons between the treatment modalities are largely unchanged whether physical or signaling-adjusted dose is compared. Conclusions Although incorporating cellular signaling significantly affects cell killing in low-dose regions and suggests a different interpretation for many phenomena, their effect in high-dose regions for typical planning techniques is comparatively small. This indicates that the significant signaling effects observed in vitro are not contradicted by comparison with clinical observations. Future investigations are needed to validate these effects in vivo and to quantify their ranges and potential impact on more advanced radiation therapy techniques.

Dose, dose-rate and field size effects on cell survival following exposure to non-uniform radiation fields

For the delivery of intensity-modulated radiation therapy (IMRT), highly modulated fields are used to achieve dose conformity across a target tumour volume. Recent in vitro evidence has demonstrated significant alterations in cell survival occurring out-of-field which cannot be accounted for on the basis of scattered dose. The radiobiological effect of area, dose and dose-rate on out-of-field cell survival responses following exposure to intensity-modulated radiation fields is presented in this study. Cell survival was determined by clonogenic assay in human prostate cancer (DU-145) and primary fibroblast (AG0-1522) cells following exposure to different modulated field configurations delivered using a X-Rad 225 kVp x-ray source. Uniform survival responses were compared to in- and out-of-field responses in which 25-99% of the cell population was shielded. Dose delivered to the out-of-field region was varied from 1.6-37.2% of that delivered to the in-field region using different levels of brass shielding. Dose rate effects were determined for 0.2-4 Gy min⁻¹ for uniform and modulated exposures with no effect seen in- or out-of-field. Survival responses showed little dependence on dose rate and area in- and out-of-field with a trend towards increased survival with decreased in-field area. Out-of-field survival responses were shown to scale in proportion to dose delivered to the in-field region and also local dose delivered out-of-field. Mathematical modelling of these findings has shown survival response to be highly dependent on dose delivered in- and out-of-field but not on area or dose rate. These data provide further insight into the radiobiological parameters impacting on cell survival following exposure to modulated irradiation fields highlighting the need for refinement of existing radiobiological models to incorporate non-targeted effects and modulated dose distributions.

Impact of using different radiation therapy techniques in breat cancer: contralateral breast dose

RESUMO: O cancro de mama e o mais frequente diagnoticado a indiv duos do sexo feminino. O conhecimento cientifico e a tecnologia tem permitido a cria ção de muitas e diferentes estrat egias para tratar esta patologia. A Radioterapia (RT) est a entre as diretrizes atuais para a maioria dos tratamentos de cancro de mama. No entanto, a radia ção e como uma arma de dois canos: apesar de tratar, pode ser indutora de neoplasias secund arias. A mama contralateral (CLB) e um orgão susceptivel de absorver doses com o tratamento da outra mama, potenciando o risco de desenvolver um tumor secund ario. Nos departamentos de radioterapia tem sido implementadas novas tecnicas relacionadas com a radia ção, com complexas estrat egias de administra ção da dose e resultados promissores. No entanto, algumas questões precisam de ser devidamente colocadas, tais como: E seguro avançar para tecnicas complexas para obter melhores indices de conformidade nos volumes alvo, em radioterapia de mama? O que acontece aos volumes alvo e aos tecidos saudaveis adjacentes? Quão exata e a administração de dose? Quais são as limitações e vantagens das técnicas e algoritmos atualmente usados? A resposta a estas questões e conseguida recorrendo a m etodos de Monte Carlo para modelar com precisão os diferentes componentes do equipamento produtor de radia ção(alvos, ltros, colimadores, etc), a m de obter uma descri cão apropriada dos campos de radia cão usados, bem como uma representa ção geometrica detalhada e a composição dos materiais que constituem os orgãos e os tecidos envolvidos. Este trabalho visa investigar o impacto de tratar cancro de mama esquerda usando diferentes tecnicas de radioterapia f-IMRT (intensidade modulada por planeamento direto), IMRT por planeamento inverso (IMRT2, usando 2 feixes; IMRT5, com 5 feixes) e DCART (arco conformacional dinamico) e os seus impactos em irradia ção da mama e na irradia ção indesejada dos tecidos saud aveis adjacentes. Dois algoritmos do sistema de planeamento iPlan da BrainLAB foram usados: Pencil Beam Convolution (PBC) e Monte Carlo comercial iMC. Foi ainda usado um modelo de Monte Carlo criado para o acelerador usado (Trilogy da VARIAN Medical Systems), no c odigo EGSnrc MC, para determinar as doses depositadas na mama contralateral. Para atingir este objetivo foi necess ario modelar o novo colimador multi-laminas High- De nition que nunca antes havia sido simulado. O modelo desenvolvido est a agora disponí vel no pacote do c odigo EGSnrc MC do National Research Council Canada (NRC). O acelerador simulado foi validado com medidas realizadas em agua e posteriormente com c alculos realizados no sistema de planeamento (TPS).As distribui ções de dose no volume alvo (PTV) e a dose nos orgãos de risco (OAR) foram comparadas atrav es da an alise de histogramas de dose-volume; an alise estati stica complementar foi realizadas usando o software IBM SPSS v20. Para o algoritmo PBC, todas as tecnicas proporcionaram uma cobertura adequada do PTV. No entanto, foram encontradas diferen cas estatisticamente significativas entre as t ecnicas, no PTV, nos OAR e ainda no padrão da distribui ção de dose pelos tecidos sãos. IMRT5 e DCART contribuem para maior dispersão de doses baixas pelos tecidos normais, mama direita, pulmão direito, cora cão e at e pelo pulmão esquerdo, quando comparados com as tecnicas tangenciais (f-IMRT e IMRT2). No entanto, os planos de IMRT5 melhoram a distribuição de dose no PTV apresentando melhor conformidade e homogeneidade no volume alvo e percentagens de dose mais baixas nos orgãos do mesmo lado. A t ecnica de DCART não apresenta vantagens comparativamente com as restantes t ecnicas investigadas. Foram tamb em identi cadas diferen cas entre os algoritmos de c alculos: em geral, o PBC estimou doses mais elevadas para o PTV, pulmão esquerdo e cora ção, do que os algoritmos de MC. Os algoritmos de MC, entre si, apresentaram resultados semelhantes (com dferen cas at e 2%). Considera-se que o PBC não e preciso na determina ção de dose em meios homog eneos e na região de build-up. Nesse sentido, atualmente na cl nica, a equipa da F sica realiza medi ções para adquirir dados para outro algoritmo de c alculo. Apesar de melhor homogeneidade e conformidade no PTV considera-se que h a um aumento de risco de cancro na mama contralateral quando se utilizam t ecnicas não-tangenciais. Os resultados globais dos estudos apresentados confirmam o excelente poder de previsão com precisão na determinação e c alculo das distribui ções de dose nos orgãos e tecidos das tecnicas de simulação de Monte Carlo usados.---------ABSTRACT:Breast cancer is the most frequent in women. Scienti c knowledge and technology have created many and di erent strategies to treat this pathology. Radiotherapy (RT) is in the actual standard guidelines for most of breast cancer treatments. However, radiation is a two-sword weapon: although it may heal cancer, it may also induce secondary cancer. The contralateral breast (CLB) is a susceptible organ to absorb doses with the treatment of the other breast, being at signi cant risk to develop a secondary tumor. New radiation related techniques, with more complex delivery strategies and promising results are being implemented and used in radiotherapy departments. However some questions have to be properly addressed, such as: Is it safe to move to complex techniques to achieve better conformation in the target volumes, in breast radiotherapy? What happens to the target volumes and surrounding healthy tissues? How accurate is dose delivery? What are the shortcomings and limitations of currently used treatment planning systems (TPS)? The answers to these questions largely rely in the use of Monte Carlo (MC) simulations using state-of-the-art computer programs to accurately model the di erent components of the equipment (target, lters, collimators, etc.) and obtain an adequate description of the radiation elds used, as well as the detailed geometric representation and material composition of organs and tissues. This work aims at investigating the impact of treating left breast cancer using di erent radiation therapy (RT) techniques f-IMRT (forwardly-planned intensity-modulated), inversely-planned IMRT (IMRT2, using 2 beams; IMRT5, using 5 beams) and dynamic conformal arc (DCART) RT and their e ects on the whole-breast irradiation and in the undesirable irradiation of the surrounding healthy tissues. Two algorithms of iPlan BrainLAB TPS were used: Pencil Beam Convolution (PBC)and commercial Monte Carlo (iMC). Furthermore, an accurate Monte Carlo (MC) model of the linear accelerator used (a Trilogy R VARIANR) was done with the EGSnrc MC code, to accurately determine the doses that reach the CLB. For this purpose it was necessary to model the new High De nition multileaf collimator that had never before been simulated. The model developed was then included on the EGSnrc MC package of National Research Council Canada (NRC). The linac was benchmarked with water measurements and later on validated against the TPS calculations. The dose distributions in the planning target volume (PTV) and the dose to the organs at risk (OAR) were compared analyzing dose-volume histograms; further statistical analysis was performed using IBM SPSS v20 software. For PBC, all the techniques provided adequate coverage of the PTV. However, statistically significant dose di erences were observed between the techniques, in the PTV, OAR and also in the pattern of dose distribution spreading into normal tissues. IMRT5 and DCART spread low doses into greater volumes of normal tissue, right breast, right lung, heart and even the left lung than tangential techniques (f-IMRT and IMRT2). However,IMRT5 plans improved distributions for the PTV, exhibiting better conformity and homogeneity in target and reduced high dose percentages in ipsilateral OAR. DCART did not present advantages over any of the techniques investigated. Di erences were also found comparing the calculation algorithms: PBC estimated higher doses for the PTV, ipsilateral lung and heart than the MC algorithms predicted. The MC algorithms presented similar results (within 2% di erences). The PBC algorithm was considered not accurate in determining the dose in heterogeneous media and in build-up regions. Therefore, a major e ort is being done at the clinic to acquire data to move from PBC to another calculation algorithm. Despite better PTV homogeneity and conformity there is an increased risk of CLB cancer development, when using non-tangential techniques. The overall results of the studies performed con rm the outstanding predictive power and accuracy in the assessment and calculation of dose distributions in organs and tissues rendered possible by the utilization and implementation of MC simulation techniques in RT TPS.

Otimização de esquemas terapêuticos do carcinoma da próstata envolvendo braquiterapia de baixa taxa de dose e radioterapia externa : abordagens física e radiobiológica

RESUMO: Este trabalho teve como objetivo a determinação de esquemas de tratamento alternativos para o carcinoma da próstata com radioterapia externa (EBRT) e braquiterapia de baixa taxa de dose (LDRBT) com implantes permanentes de Iodo-125, biologicamente equivalentes aos convencionalmente usados na prática clínica, com recurso a modelos teóricos e a métodos de Monte Carlo (MC). Os conceitos de dose biológica efetiva (BED) e de dose uniforme equivalente (EUD) foram utilizados, com o modelo linear-quadrático (LQ), para a determinação de regimes de tratamento equivalentes. Numa primeira abordagem, utilizou-se a BED para determinar: 1) esquemas hipofracionados de EBRT mantendo as complicações retais tardias de regimes convencionais com doses totais de 75,6 Gy, 77,4 Gy, 79,2 Gy e 81,0 Gy; e 2) a relação entre as doses totais de EBRT e LDRBT de modo a manter a BED do regime convencional de 45 Gy de EBRT e 110 Gy de LDRBT. Numa segunda abordagem, recorreu-se ao código de MC MCNPX para a simulação de distribuições de dose de EBRT e LDRBT em dois fantomas de voxel segmentados a partir das imagens de tomografia computorizada de pacientes com carcinoma da próstata. Os resultados das simulações de EBRT e LDRBT foram somados e determinada uma EUD total de forma a obterem-se: 1) esquemas equivalentes ao tratamento convencional de 25 frações de 1,8 Gy de EBRT em combinação com 110 Gy de LDRBT; e 2) esquemas equivalentes a EUD na próstata de 67 Gy, 72 Gy, 80 Gy, 90 Gy, 100 Gy e 110 Gy. Em todos os resultados nota-se um ganho terapêutico teórico na utilização de esquemas hipofracionados de EBRT. Para uma BED no reto equivalente ao esquema convencional, tem-se um aumento de 2% na BED da próstata com menos 5 frações. Este incremento dá-se de forma cada vez mais visível à medida que se reduz o número de frações, sendo da ordem dos 10-11% com menos 20 frações e dos 35-45% com menos 40 frações. Considerando os resultados das simulações de EBRT, obteve-se uma EUD média de 107 Gy para a próstata e de 42 Gy para o reto, com o esquema convencional de 110 Gy de LDRBT, seguidos de 25 frações de 1,8 Gy de EBRT. Em termos de probabilidade de controlo tumoral (igual EUD), é equivalente a este tratamento a administração de EBRT em 66 frações de 1,8 Gy, 56 de 2 Gy, 40 de 2,5 Gy, 31 de 3 Gy, 20 de 4 Gy ou 13 de 5 Gy. Relativamente à administração de 66 frações de 1,8 Gy, a EUD generalizada no reto reduz em 6% com o recurso a frações de 2,5 Gy e em 10% com frações de 4 Gy. Determinou-se uma BED total de 162 Gy para a administração de 25 frações de 1,8 Gy de EBRT em combinação com 110 Gy de LDRBT. Variando-se a dose total de LDRBT (TDLDRBT) em função da dose total de EBRT (TDEBRT), de modo a garantir uma BED de 162 Gy, obteve-se a seguinte relação:.......... Os resultados das simulações mostram que a EUD no reto diminui com o aumento da dose total de LDRBT para dose por fração de EBRT (dEBRT) inferiores a 2, Gy e aumenta para dEBRT a partir dos 3 Gy. Para quantidades de TDLDRBT mais baixas (<50 Gy), o reto beneficia de frações maiores de EBRT. À medida que se aumenta a TDLDRBT, a EUD generalizada no reto torna-se menos dependente da dEBRT. Este trabalho mostra que é possível a utilização de diferentes regimes de tratamento para o carcinoma da próstata com radioterapia que possibilitem um ganho terapêutico, quer seja administrando uma maior dose biológica com efeitos tardios constantes, quer mantendo a dose no tumor e diminuindo a toxicidade retal. A utilização com precaução de esquemas hipofracionados de EBRT, para além do benefício terapêutico, pode trazer vantagens ao nível da conveniência para o paciente e economia de custos. Os resultados das simulações deste estudo e conversão para doses de efeito biológico para o tratamento do carcinoma da próstata apresentam linhas de orientação teórica de interesse para novos ensaios clínicos. --------------------------------------------------ABSTRACT: The purpose of this work was to determine alternative radiotherapy regimens for the treatment of prostate cancer using external beam radiotherapy (EBRT) and low dose-rate brachytherapy (LDRBT) with Iodine-125 permanent implants which are biologically equivalent to conventional clinical treatments, by the use of theoretical models and Monte Carlo techniques. The concepts of biological effective dose (BED) and equivalent uniform dose (EUD), together with the linear-quadratic model (LQ), were used for determining equivalent treatment regimens. In a first approach, the BED concept was used to determine: 1) hypofractionated schemes of EBRT maintaining late rectal complications as with the conventional regimens with total doses of 75.6 Gy, 77.4 Gy, 79.2 Gy and 81.0 Gy; and 2) the relationship between total doses of EBRT and LDRBT in order to keep the BED of the conventional treatment of 45 Gy of EBRT and 110 Gy of LDRBT. In a second approach, the MC code MCNPX was used for simulating dose distributions of EBRT and LDRBT in two voxel phantoms segmented from the computed tomography of patients with prostate cancer. The results of the simulations of EBRT and LDRBT were added up and given an overall EUD in order to obtain: 1) equivalent to conventional treatment regimens of 25 fraction of 1.8 Gy of EBRT in combination with 110Gy of LDRBT; and 2) equivalent schemes of EUD of 67 Gy, 72 Gy, 80 Gy, 90 Gy, 100 Gy, and 110Gy to the prostate. In all the results it is noted a therapeutic gain using hypofractionated EBRT schemes. For a rectal BED equivalent to the conventional regimen, an increment of 2% in the prostate BED was achieved with less 5 fractions. This increase is visibly higher as the number of fractions decrease, amounting 10-11% with less 20 fractions and 35-45% with less 20 fractions. Considering the results of the EBRT simulations an average EUD of 107 Gy was achieved for the prostate and of 42 Gy for the rectum with the conventional scheme of 110 Gy of LDRBT followed by 25 fractions of 1.8 Gy of EBRT. In terms of tumor control probability (same EUD) it is equivalent to this treatment, for example, delivering the EBRT in 66 fractions of 1.8 Gy, 56 fractions of 2 Gy, 40 fractions of 2.5 Gy, 31 fractions of 3 Gy, 20 fractions of 4 Gy or 13 fractions of 5 Gy. Regarding the use of 66 fractions of 1.8 Gy, the rectum EUD is reduced to 6% with 2.5 Gy per fraction and to 10% with 4 Gy. A total BED of 162 Gy was achieved for the delivery of 25 fractions of 1.8 Gy of EBRT in combination with 110 Gy of LDRBT. By varying the total dose of LDRBT (TDLDRBT) with the total dose of EBRT (TDEBRT) so as to ensure a BED of 162 Gy, the following relationship was obtained: ....... The simulation results show that the rectum EUD decreases with the increase of the TDLDRBT, for EBRT dose per fracion (dEBRT) less than 2.5 Gy and increases for dEBRT above 3 Gy. For lower amounts of TDLDRBT (< 50Gy), the rectum benefits of larger EBRT fractions. As the TDLDRBT increases, the rectum gEUD becomes less dependent on the dEBRT. The use of different regimens which enable a therapeutic gain, whether deivering a higher dose with the same late biological effects or maintaining the dose to the tumor and reducing rectal toxicity is possible. The use with precaution of hypofractionated regimens, in addition to the therapeutic benefit, can bring advantages in terms of convenience for the patient and cost savings. The simulation results of this study together with the biological dose conversion for the treatment of prostate cancer serve as guidelines of interest for new clinical trials.

Implantation et validation d’un modèle Monte Carlo du Cyberknife dans un outil de calcul de dose clinique

Le travail de modélisation a été réalisé à travers EGSnrc, un logiciel développé par le Conseil National de Recherche Canada.

Tomotherapy dose distribution verification using MAGIC-f polymer gel dosimetry

Purpose: This paper presents the application of MAGIC-f gel in a three-dimensional dose distribution measurement and its ability to accurately measure the dose distribution from a tomotherapy unit. Methods: A prostate intensity-modulated radiation therapy (IMRT) irradiation was simulated in the gel phantom and the treatment was delivered by a TomoTherapy equipment. Dose distribution was evaluated by the R2 distribution measured in magnetic resonance imaging. Results: A high similarity was found by overlapping of isodoses of the dose distribution measured with the gel and expected by the treatment planning system (TPS). Another analysis was done by comparing the relative absorbed dose profiles in the measured and in the expected dose distributions extracted along indicated lines of the volume and the results were also in agreement. The gamma index analysis was also applied to the data and a high pass rate was achieved (88.4% for analysis using 3%/3 mm and of 96.5% using 4%/4 mm). The real three-dimensional analysis compared the dose-volume histograms measured for the planning volumes and expected by the treatment planning, being the results also in good agreement by the overlapping of the curves. Conclusions: These results show that MAGIC-f gel is a promise for tridimensional dose distribution measurements. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4704496]

An evaluation of dosimetric characteristics of MAGIC gel modified by adding formaldehyde (MAGIC-f)

Purpose: To evaluate the dosimetric characteristics of a new formulation of MAGIC gel, called MAGIC-f, which contains the addition of 3.3% formaldehyde, resulting in a gel with increased thermal stability. Methods: MAGIC-f gel was prepared and stored in hermetically sealed plastic containers. After irradiation, magnetic resonance images (MRI) were acquired to evaluate dose and dose distribution. Dosimetric characterization was performed by means of depth dose measurements, dose response sensitivity and linearity, temporal stability, energy and dose rate dependence, dose integration using sequential beams, temperature influence during MRI acquisition and dose distribution integrity. Results: MAGIC-f depth dose measurements are compatible with the dosimetric table data within +/- 4% uncertainty. The dosimeter's R-2 response varies linearly with dose at least from 0 to 6 Gy. The time-course of the sensitivity of the dosimeter following irradiation, indicated stabilization after 2 weeks. The dosimeter's response to irradiation was altered by 6% when increasing the energy from cobalt beams to 10 MV beams. The dose rate dependence of this new formulation of gel dosimeter is small: less than 2.5% for a variation from 200 to 500 cGy/min, and the dependence with the fractionation scheme is about 50% smaller than for standard MAGIC gel, The dependence on scanning temperature was also verified, and the integrity of the dose distribution was confirmed for a period of 90 days. Conclusions: The results demonstrate the applicability of this new dosimeter in tridimensional dose distribution measurements. (C) 2012 Elsevier Ltd. All rights reserved.

Validation of the Swiss Monte Carlo Plan for a static and dynamic 6 MV photon beam

Monte Carlo (MC) based dose calculations can compute dose distributions with an accuracy surpassing that of conventional algorithms used in radiotherapy, especially in regions of tissue inhomogeneities and surface discontinuities. The Swiss Monte Carlo Plan (SMCP) is a GUI-based framework for photon MC treatment planning (MCTP) interfaced to the Eclipse treatment planning system (TPS). As for any dose calculation algorithm, also the MCTP needs to be commissioned and validated before using the algorithm for clinical cases. Aim of this study is the investigation of a 6 MV beam for clinical situations within the framework of the SMCP. In this respect, all parts i.e. open fields and all the clinically available beam modifiers have to be configured so that the calculated dose distributions match the corresponding measurements. Dose distributions for the 6 MV beam were simulated in a water phantom using a phase space source above the beam modifiers. The VMC++ code was used for the radiation transport through the beam modifiers (jaws, wedges, block and multileaf collimator (MLC)) as well as for the calculation of the dose distributions within the phantom. The voxel size of the dose distributions was 2mm in all directions. The statistical uncertainty of the calculated dose distributions was below 0.4%. Simulated depth dose curves and dose profiles in terms of [Gy/MU] for static and dynamic fields were compared with the corresponding measurements using dose difference and γ analysis. For the dose difference criterion of ±1% of D(max) and the distance to agreement criterion of ±1 mm, the γ analysis showed an excellent agreement between measurements and simulations for all static open and MLC fields. The tuning of the density and the thickness for all hard wedges lead to an agreement with the corresponding measurements within 1% or 1mm. Similar results have been achieved for the block. For the validation of the tuned hard wedges, a very good agreement between calculated and measured dose distributions was achieved using a 1%/1mm criteria for the γ analysis. The calculated dose distributions of the enhanced dynamic wedges (10°, 15°, 20°, 25°, 30°, 45° and 60°) met the criteria of 1%/1mm when compared with the measurements for all situations considered. For the IMRT fields all compared measured dose values agreed with the calculated dose values within a 2% dose difference or within 1 mm distance. The SMCP has been successfully validated for a static and dynamic 6 MV photon beam, thus resulting in accurate dose calculations suitable for applications in clinical cases.

Generalized eMC implementation for Monte Carlo dose calculation of electron beams from different machine types

The electron Monte Carlo (eMC) dose calculation algorithm available in the Eclipse treatment planning system (Varian Medical Systems) is based on the macro MC method and uses a beam model applicable to Varian linear accelerators. This leads to limitations in accuracy if eMC is applied to non-Varian machines. In this work eMC is generalized to also allow accurate dose calculations for electron beams from Elekta and Siemens accelerators. First, changes made in the previous study to use eMC for low electron beam energies of Varian accelerators are applied. Then, a generalized beam model is developed using a main electron source and a main photon source representing electrons and photons from the scattering foil, respectively, an edge source of electrons, a transmission source of photons and a line source of electrons and photons representing the particles from the scrapers or inserts and head scatter radiation. Regarding the macro MC dose calculation algorithm, the transport code of the secondary particles is improved. The macro MC dose calculations are validated with corresponding dose calculations using EGSnrc in homogeneous and inhomogeneous phantoms. The validation of the generalized eMC is carried out by comparing calculated and measured dose distributions in water for Varian, Elekta and Siemens machines for a variety of beam energies, applicator sizes and SSDs. The comparisons are performed in units of cGy per MU. Overall, a general agreement between calculated and measured dose distributions for all machine types and all combinations of parameters investigated is found to be within 2% or 2 mm. The results of the dose comparisons suggest that the generalized eMC is now suitable to calculate dose distributions for Varian, Elekta and Siemens linear accelerators with sufficient accuracy in the range of the investigated combinations of beam energies, applicator sizes and SSDs.

Leaf transmission reduction using moving jaws for dynamic MLC IMRT

The aim of this work is to investigate to what extent it is possible to use the secondary collimator jaws to reduce the transmitted radiation through the multileaf collimator (MLC) during an intensity modulated radiation therapy (IMRT). A method is developed and introduced where the jaws follow the open window of the MLC dynamically (dJAW method). With the aid of three academic cases (Closed MLC, Sliding-gap, and Chair) and two clinical cases (prostate and head and neck) the feasibility of the dJAW method and the influence of this method on the applied dose distributions are investigated. For this purpose the treatment planning system Eclipse and the Research-Toolbox were used as well as measurements within a solid water phantom were performed. The transmitted radiation through the closed MLC leads to an inhomogeneous dose distribution. In this case, the measured dose within a plane perpendicular to the central axis differs up to 40% (referring to the maximum dose within this plane) for 6 and 15 MV. The calculated dose with Eclipse is clearly more homogeneous. For the Sliding-gap case this difference is still up to 9%. Among other things, these differences depend on the depth of the measurement within the solid water phantom and on the application method. In the Chair case, the dose in regions where no dose is desired is locally reduced by up to 50% using the dJAW method instead of the conventional method. The dose inside the chair-shaped region decreased up to 4% if the same number of monitor units (MU) as for the conventional method was applied. The undesired dose in the volume body minus the planning target volume in the clinical cases prostate and head and neck decreased up to 1.8% and 1.5%, while the number of the applied MU increased up to 3.1% and 2.8%, respectively. The new dJAW method has the potential to enhance the optimization of the conventional IMRT to a further step.

Collapsed cone convolution and analytical anisotropic algorithm dose calculations compared to VMC++ Monte Carlo simulations in clinical cases

The purpose of this work was to study and quantify the differences in dose distributions computed with some of the newest dose calculation algorithms available in commercial planning systems. The study was done for clinical cases originally calculated with pencil beam convolution (PBC) where large density inhomogeneities were present. Three other dose algorithms were used: a pencil beam like algorithm, the anisotropic analytic algorithm (AAA), a convolution superposition algorithm, collapsed cone convolution (CCC), and a Monte Carlo program, voxel Monte Carlo (VMC++). The dose calculation algorithms were compared under static field irradiations at 6 MV and 15 MV using multileaf collimators and hard wedges where necessary. Five clinical cases were studied: three lung and two breast cases. We found that, in terms of accuracy, the CCC algorithm performed better overall than AAA compared to VMC++, but AAA remains an attractive option for routine use in the clinic due to its short computation times. Dose differences between the different algorithms and VMC++ for the median value of the planning target volume (PTV) were typically 0.4% (range: 0.0 to 1.4%) in the lung and -1.3% (range: -2.1 to -0.6%) in the breast for the few cases we analysed. As expected, PTV coverage and dose homogeneity turned out to be more critical in the lung than in the breast cases with respect to the accuracy of the dose calculation. This was observed in the dose volume histograms obtained from the Monte Carlo simulations.

Conversion of CT numbers into tissue parameters for Monte Carlo dose calculations: a multi-centre study

The conversion of computed tomography (CT) numbers into material composition and mass density data influences the accuracy of patient dose calculations in Monte Carlo treatment planning (MCTP). The aim of our work was to develop a CT conversion scheme by performing a stoichiometric CT calibration. Fourteen dosimetrically equivalent tissue subsets (bins), of which ten bone bins, were created. After validating the proposed CT conversion scheme on phantoms, it was compared to a conventional five bin scheme with only one bone bin. This resulted in dose distributions D(14) and D(5) for nine clinical patient cases in a European multi-centre study. The observed local relative differences in dose to medium were mostly smaller than 5%. The dose-volume histograms of both targets and organs at risk were comparable, although within bony structures D(14) was found to be slightly but systematically higher than D(5). Converting dose to medium to dose to water (D(14) to D(14wat) and D(5) to D(5wat)) resulted in larger local differences as D(5wat) became up to 10% higher than D(14wat). In conclusion, multiple bone bins need to be introduced when Monte Carlo (MC) calculations of patient dose distributions are converted to dose to water.