Background & Purpose: The current standard dosimetry in brachytherapy treatment planning, the TG-43 formalism, ignore the presence of non-water media and finite patient dimensions. This can cause clinically relevant errors in dose estimates. To over- come the limitations of the TG-43 formalism, Model-Based Dose Calculation Algorithms (MBDCAs) have evolved. One of the commercial available MBDCAs is the Advanced Collapsed cone Engine (ACE) by Elekta. In ACE, the total dose is divided into three components, the primary, the first-scattered and the multiple-scattered dose, where the two last mentioned are calculated by the means of the Collapsed Cone Algorithm. In this study the performance of ACE has been investigated. The study has been di- vided into 2 parts, where the aim of part 1 was to analyze the relationship between the so called discretization artifacts, caused by the collapsed cone approximation, and the number of dwell positions. The severeness of the artifact is thought to decrease as the number of dwell positions are increased. The second part focus on ACE’s behavior in cortical bone, with the aim to form a hypothesis (explanation and solution) to the previously observed dose underestimation of the dose to bone made by ACE. Materials and Methods: The generic 192Ir source, the Oncentra Brachy (OcB) treatment planning system (TPS) and the Monte Carlo (MC) platform ALGEBRA have been utilized. In the first part of the study, six source configurations, all with a different number of dwell positions, were created and placed in the center of large water phantoms, i.e. under TG-43 conditions in which the TG-43 formalism can be assumed to yield a high accuracy of the estimated dose. The accuracy of ACE has been judged by its’ deviation from TG-43. In the second part of the study, a cubic source configuration, of 27 dwell positions, was positioned at the center of a cubic water phantom. Three cases where constructed, with a small cortical bone heterogeneity positioned at different distances from the source configu- ration. The ACE calculated dose distribution has been divided into its’ three constituents. The accuracy of ACE and TG-43 has been judged by its’ deviation from MC. Results: Part 1 showed that increasing the number of dwell positions does not guar- antee an improved accuracy of ACE. Local dose difference ratios of > 2%, caused by the artifacts, were mainly located outside the 5% isodose line. A general dose underestima- tion was observed in ACE, with an increased magnitude as the dose level decreased. The majority of local dose difference ratios below -4% were found where the multi-resolution voxelization grid of ACE has a voxel size of ≥23 mm3, that is at a distance of ≥8 cm from the closest dwell position when using the ACE standard accuracy level. In part 2, ACE underestimated the dose to cortical bone, with an increased magnitude as the bone was positioned farther away from the source configuration. The TG-43 formalism gave slightly better estimates of the mean dose to bone than ACE, especially at higher dose levels. For a mean dose to the cortical bone heterogeneity equal to 45% of the prescribed dose, TG-43 and ACE underestimated the mean dose with 1% and 4%, respectively. The estimated mean dose to a volume located directly behind the heterogeneity agreed within 1% between ACE and MC. However, an increased amount of positive local dose difference ratios were observed in this volume. Conclusions: Increasing the number of dwell positions cause a ”blurring” effect of the artifact, but may also increase the fluence gradient. In such situations the severeness of the artifact may not be improved. In patient cases the dwell positions are usually added in a more random manner which may favor the ”blurring effect”. The underestimations observed in ACE are thought to be caused by both the multiple- resolution voxelization grid of ACE and the relationship between the dimensions of the phantom in which the multiple-scattered kernel has been generated and the current calcu- lation volume. ACE was unsuccessful to predict the dose to cortical bone, and should hence be used with caution when cortical bone is an organ at risk, as long as the problem remains. The results indicates that the error in ACE is located in the scatter dose calculations and that the heterogeneity cause ACE to displace the dose. The error is thought to be located in the multiple-scattered dose component, which was also shown by Terribilni et al.. A hypothesis is that the problem is caused by the neglected effect of media dependent absorption coefficients in the multiple-scattered dose calculation. A suggested solution, left to be proven, is to use effective attenuation scaling factors.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12916号 / 論医博第2091号 / 新制||医||1009(附属図書館) / 32126 / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 伊達 洋至, 教授 鈴木 実 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

A prerequisite for modern radiotherapy is the ability to accurately determine the absorbed dose (D) that is given to the patient. The subject of this thesis has been to develop and evaluate efficient dose calculation models for high-energy photon beams delivered by linear accelerators. Even though the considered calculation models are general, the work has been focused on quality assurance (QA) tools used to independently verify the dose for individual treatment plans. The purpose of this verification is to guarantee patient safety and to improve the treatment outcome. Furthermore, a vital part of this work has been to explore the prospect of estimating the dose calculation uncertainties associated with individual treatment setups. A discussion on how such uncertainty estimations can facilitate improved clinical QA procedures by providing appropriate action levels has also been included within the scope of this thesis. In order to enable efficient modelling of the physical phenomena that are involved in dose output calculations it is convenient to divide them into two main categories; the first one dealing with the radiation exiting the accelerator’s treatment head and a second one associated with the subsequent energy deposition processes. A multi-source model describing the distribution of energy fluence emitted from the treatment head per delivered monitor unit (MU) is presented and evaluated through comparisons with measurements in multiple photon beams and collimator settings. The calculations show close agreement with the extensive set of experimental data, generally within +/-1% of corresponding measurements. The energy (dose) deposition in the irradiated object has been modelled through a photon pencil kernel solely based on a beam quality index (TPR20,10). This model was evaluated in a similar manner as the multi-source model at three different treatment depths. A separate study was focused on the specific difficulties associated with dose calculations in points located at a distance from the central beam axis. Despite the minimal input data required to characterize individual photon beams, the accuracy proved to be very good when comparing the calculated results with experimental data. The evaluated calculation models were finally used to analyse how well the lateral dose distributions from typical megavoltage photon beams are optimized with respect to the resulting beam flatness characteristics. The results did not reveal any obvious reasons why different manufacturers should provide different lateral dose distributions. Furthermore, the performed lateral optimizations indicate that there is room for improved flatness performance for the investigated linear accelerators.

Radiation therapy with light ions improves treatment outcome for a number of tumor types. The advantageous dose distributions of light ion beams en-able exceptional target conformity, which assures high dose delivery to the tumor while minimizing the dose to surrounding normal tissues. The demand of high target conformity necessitates development of accurate methods to calculate absorbed dose distributions. This is especially important for heavy charged particle irradiation, where the patient is exposed to a complex radia-tion field of primary and secondary ions. The presented approach combines accurate Monte Carlo calculations using the SHIELD-HIT07 code with a fast analytical pencil beam model, to pro-vide dose distributions of light ions. The developed model allows for ana-lytical descriptions of multiple scattering and energy loss straggling proc-esses of both primary ions and fragments, transported in tissue equivalent media. By applied parameterization of the radial spread of fragments, im-proved description of radial dose distributions at every depth is obtained. The model provides a fast and accurate tool of practical value in clinical work. Compared to conventional radiation modalities, an enhanced tissue response is seen after light ion irradiation and biological optimization calls for accu-rate model description and prediction of the biological effects of ion expo-sure. In a joint study, the performance of some radiobiological models is compared for facilitating the development towards more robust and precise models. Specifically, cell survival after exposure to various ion species is modeled by a fast analytical cellular track structure approach in conjunction with a simple track-segment model of ion beam transport. Although the stud-ies show that descriptions of complex biological effects of ion beams, as given by simple radiobiological models, are approximate, the models may yet be useful in analyzing clinical results and designing new strategies for ion therapy.

IMRT uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI), a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or “blurred” dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUDf has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques. Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.

IMRT uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI), a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or “blurred” dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUDf has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques. Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.

IMRT uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI), a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or “blurred” dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUDf has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques. Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.

IMRT uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI), a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or “blurred” dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUDf has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques. Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.

The Coarse-Mesh Transport Method (COMET) is a method developed by the Computational Reactor and Medical Physics Group at Georgia Tech. Its original application was neutron transport for nuclear reactor modeling. COMET has since been shown to be effective for coupled photon-electron transport calculations where the goal is to determine the energy deposition of a photon beam. So far COMET can simulate a mono-directional, mono-energetic, spatially-flat photon beam. The goal of this thesis will be to extend COMET by adding a generalized source treatment. The new source will be able to simulate beams that vary in intensity as a function of position, angle, and energy. EGSnrc will be used to verify the accuracy of the new method for 3D photon kerma calculations.

Ce travail a été mené dans un contexte de collaboration étroite entre le Centre de Protonthérapie d’Orsay de l’Institut Curie (ICPO), Dosisoft et le laboratoire Creatis afin de mettre en place un nouveau modèle de calcul de dose pour la nouvelle salle de traitement de l’ICPO. Le projet de rénovation et d’agrandissement de ce dernier a permis l’installation d’un nouvel accélérateur ainsi que d’une nouvelle salle de traitement équipée d’un bras isocentrique de la société IBA, dans le but de diversifier les localisations des cancers traités à l’ICPO. Le premier objectif de cette thèse est de développer un ensemble de méthodologies et de nouveaux algorithmes liés au calcul de dose pour les adapter aux caractéristiques spécifiques des faisceaux délivrés par la nouvelle machine IBA, avec comme finalité de les inclure dans le logiciel Isogray de DOSIsoft. Dans un premier temps, la technique de la double diffusion est abordée en tenant compte des différences avec le système passif des lignes fixes de l’ICPO. Dans un deuxième temps, une modélisation est envisagée pour les modalités de faisceaux balayés. Le deuxième objectif est d’améliorer les modèles de calcul de dose Ray-Tracing et Pencil-Beam existants. En effet, le collimateur personnalisé du patient en fin de banc de mise en forme du faisceau pour les techniques de double diffusion et de balayage uniforme provoque une contamination de la dose délivrée au patient. Une méthodologie de réduction de cet effet a été mise en place pour le système passif de délivrance du faisceau, ainsi qu’un modèle analytique décrivant la fonction de contamination, dont les paramètres ont été validés grâce à des simulations Monte Carlo sur la plateforme GATE. Il est aussi possible d’appliquer ces méthodes aux systèmes actifs. / This work was achieved in collaboration between the Institut Curie Protontherapy Center of Orsay (ICPO), the DOSIsoft company and the CREATIS laboratory, in order to develop a new dose calculation model for the new ICPO treatment room. A new accelerator and gantry room from the IBA company were installed during the up-grade project of the protontherapy center, with the intention of enlarging the cancer localizations treated at ICPO. Developing a package of methods and new dose calculation algorithms to adapt them to the new specific characteristics of the delivered beams by the IBA system is the first goal of this PhD work. They all aim to be implemented in the DOSIsoft treatment planning software, Isogray. First, the double scattering technique is treated in taking into account major differences between the IBA system and the ICPO fixed beam lines passive system. Secondly, a model is explored for the scanned beams modality. The second objective of this work is improving the Ray-Tracing and Pencil-Beam dose calculation models already in use. For the double scattering and uniform scanning techniques, the patient personalized collimator at the end of the beam line causes indeed a patient dose distribution contamination. A reduction method of that phenomenon was set up for the passive beam system. An analytical model was developed which describes the contamination function with parameters validated through Monte-Carlo simulations on the GATE platform. It allows us to apply those methods to active scanned beams.