Dissertations / Theses on the topic 'Cancer Radiotherapy Planning'

Radiotherapy is the most widely used treatment for cancer, with 4 out of 10 cancer patients receiving radiotherapy as part of their treatment. The delineation of gross tumour volume (GTV) is crucial in the treatment of radiotherapy. An automatic contouring system would be beneficial in radiotherapy planning in order to generate objective, accurate and reproducible GTV contours. Image guided radiotherapy (IGRT) acquires patient images just before treatment delivery to allow any necessary positional correction. Consequently, real-time contouring system provides an opportunity to adopt radiotherapy on the treatment day. In this thesis, freely deformable models (FDM) and shape constrained deformable models (SCDMs) were used to automatically delineate the GTV for brain cancer and prostate cancer. Level set method (LSM) is a typical FDM which was used to contour glioma on brain MRI. A series of low level image segmentation methodologies are cascaded to form a case-wise fully automatic initialisation pipeline for the level set function. Dice similarity coefficients (DSCs) were used to evaluate the contours. Results shown a good agreement between clinical contours and LSM contours, in 93% of cases the DSCs was found to be between 60% and 80%. The second significant contribution is a novel development to the active shape model (ASM), a profile feature was selected from pre-computed texture features by minimising the Mahalanobis distance (MD) to obtain the most distinct feature for each landmark, instead of conventional image intensity. A new group-wise registration scheme was applied to solve the correspondence definition within the training data. This ASM model was used to delineated prostate GTV on CT. DSCs for this case was found between 0.75 and 0.91 with the mean DSC 0.81. The last contribution is a fully automatic active appearance model (AAM) which captures image appearance near the GTV boundary. The image appearance of inner GTV was discarded to spare the potential disruption caused by brachytherapy seeds or gold markers. This model outperforms conventional AAM at the prostate base and apex region by involving surround organs. The overall mean DSC for this case is 0.85.

External beam radiotherapy is delivered from outside the body aimed at cancer cells to damage their DNA making them unable to divide and reproduce. The beams travel through the body and may damage nearby healthy tissues unless carefully planned. Therefore, the goal of treatment plan optimization is to find the best system configuration to deliver sufficient dose to target structures while avoiding damage to healthy tissues. This thesis investigates optimization approaches for two external beam radiation therapy techniques: Intensity-Modulated Radiation Therapy (IMRT) and Volumetric-Modulated Arc Therapy (VMAT). We develop an automated treatment planning technology for IMRT which generates several high-quality treatment plans satisfying the provided requirements in a single invocation and without human guidance. Our approach is based on an existing linear programming-based fluence map optimization model that approximates dose-volume requirements using conditional value-at-risk (C-VaR) constraints. We show how the parameters of the C-VaR constraints can be used to control various metrics of treatment plan quality. A novel bi-criteria scoring based beam selection algorithm is developed which finds the best beam configuration at least ten times faster for real-life brain, prostate, and head and neck cases as compared to an exact mixed integer programming model. Patient anatomy changes due to breathing during the treatment of lung cancer need to be considered in treatment planning. To date, a single phase of the breathing cycle is typically selected for treatment and radiation is shut-off in other phases. We investigate optimization technology that finds optimal fluence maps for each phase of the breathing cycle by considering the overall dose delivered to a patient using image registration algorithms to track target structures and organs at risk. Because the optimization exploits the opportunities provided in each phase, better treatment plans are obtained. The improvements are shown on a real-life lung case. VMAT is a recent radiation treatment technology which has the potential to provide treatments in less time compared to other delivery techniques. This enhances patient comfort and allows for the treatment of more patients. We build a large-scale mixed-integer programming model for VMAT treatment plan optimization. The solution of this model is computationally prohibitive. Therefore, we develop an iterative MIP-based heuristic algorithm which solves the model multiple times on a reduced set of decision variables. We introduce valid inequalities that decrease solution times, and, more importantly, that identify higher quality integer solutions within specified time limits. Computational studies on a spinal tumor and a prostate tumor case produce clinically acceptable results.

This thesis developed predictive models and risk profiles for pre-treatment identification of suitable adaptive radiotherapy candidates, from a cohort of oropharyngeal and nasopharyngeal cancer patients. This unique prospective approach could facilitate effective implementation of head and neck cancer adaptive radiotherapy into radiotherapy departments in Australia and internationally, through forward planning and appropriate resource allocation. Predicting those patients more likely to need adaptive radiotherapy in an efficient and judicious manner provides numerous benefits to radiotherapy departments across the world and ultimately, the patients under our care.

In this thesis, a novel case-based reasoning (CBR) approach to radiotherapy treatment planning for brain cancer patients is presented. In radiotherapy, tumour cells are destroyed using ionizing radiation. For each patient, a treatment plan is generated that describes how the radiation should be applied in order to deliver a tumouricidal radiation dose while avoiding irradiation of healthy tissue and organs at risk in the vicinity of the tumour. The traditional, manual trial and error approach is a time-consuming process that depends on the experience and intuitive knowledge of medical physicists. CBR is an artificial intelligence methodology, which attempts to solve new problems based on the solutions of previously solved similar problems. In this research work, CBR is used to generate the parameters of a treatment plan by capturing the subjective and intuitive knowledge of expert medical physicists stored intrinsically in the treatment plans of similar patients treated in the past. This work focusses on the retrieval stage of the CBR system, in which given a new patient case, the most similar case in the archived case base is retrieved along with its treatment plan. A number of research issues that arise from using CBR for radiotherapy treatment planning for brain cancer are addressed. Different approaches to similarity calculation between cases are investigated and compared, in particular, the weighted nearest neighbour similarity measure and a novel non-linear, fuzzy similarity measure designed for our CBR system. A local case attribute weighting scheme has been developed that uses rules to assign attribute weights based on the values of the attributes in the new case and is compared to global attribute weighting, where the attribute weights remain constant for all target cases. A multi-phase case retrieval approach is introduced in which each phase considers one part of the solution. In addition, a framework developed for the imputation of missing values in the case base is described. The research was carried out in collaboration with medical physicists at the Nottingham University Hospitals NHS Trust, City Hospital Campus, UK. The performance of the developed methodologies was tested using brain cancer patient cases obtained from the City Hospital. The results obtained show that the success rate of the retrieval mechanism provides a good starting point for adaptation, the next phase in development for the CBR system. The developed automated CBR system will assist medical physicists in quickly generating treatment plans and can also serve as a teaching and training aid for junior, inexperienced medical physicists. In addition, the developed methods are generic in nature and can be adapted to be used in other CBR or intelligent decision support systems for other complex, real world, problem domains that highly depend on subjective and intuitive knowledge.

This dissertation addresses the issue of robustness in proton therapy treatment planning for cancer treatment. Proton therapy is considered to be advantageous in treating most childhood cancers and certain adult cancers, including those of the skull base, spine and head and neck. Protons, unlike X-rays, have a finite range highly dependent on the electron density of the material they are traversing, resulting in a steep dose gradient at the distal edge of the Bragg peak. These characteristics, together with advancements in computation and technology have led to the ability to plan and deliver treatments with greater conformality, sparing normal tissue and organs at risk. Radiotherapy treatment plans aim to meet set dosimetric constraints, and meet them at every fraction. Plan robustness is a measure of deviation between the delivered dose distribution and the planned dose distribution. Due to the same characteristics that make protons advantageous, conventional means of using margins to create a Planning Target Volume (PTV) to ensure plan robustness are inadequate. Additional to this, without a PTV, a new method of analysing plan quality is required in proton therapy. My original contribution to the knowledge in this area is the demonstration of how site- and centre- specific robustness constraints can be established. Robustness constraints can be used both for proton plan analysis and to identify patients that require plans of greater individualisation. I have also used the daily volumetric imaging from patients previously treated with conventional radiotherapy to quantify range uncertainty from inter- and intra-fraction motion. These new methods of both quantifying and analysing the change in proton range in the patient can aid in the choice of beam directions, provide input into a multi- criteria optimisation algorithm or can be used as criteria to determine when adaptive planning may be required. This greater understanding in range uncertainty better informs the planner on how best to balance the trade-off between plan conformality and robustness in proton therapy. This research is directly relevant to furthering the knowledge base in light of HM Government pledging £250 million to build two proton centres in England, to treat NHS patients from 2018. Use of methods described in this dissertation will aid in the establishment of clear and pre-defined protocols for treating patients in the future.

In this thesis, a two-part investigation was conducted to determine methods of reducing the inaccuracy in the treatment of solid tumors in the lung. In the first part, a visual feedback system was investigated for use during respiratory gating procedures, both during simulation and treatment. The visual feedback system was installed in the clinic and was used by three patients during radiotherapy and by approximately 15 patients during simulation. The use of the visual feedback was found to increase the regularity of the patients’ breathing patterns and improved the ability of the gating technique to compensate for internal tumor motion. The second part consisted of a comparison of the dose distribution algorithms of the Eclipse treatment planning system with dose calculations performed using Monte Carlo methods based on the EGSnrc and DOSXYZnrc user codes for BEAMnrc. Four patients with lung tumors, whose treatment plans called for small, 18 MV photon fields, were recalculated using both systems. Results showed that the algorithms used by the TPS consistently overestimated the dose in the lung, due to the lack of lateral electron equilibrium in the lung tissue.
Dans ce mémoire, une enquête en deux parties à été entreprise pour analyser des méthodes permettant la réduction d’erreurs dans le traitement des cancers pulmonaires. Dans la première partie de l’enquête, nous analysons un système de « feedback » visuel utilisé avec les procédures de « gating » en simulation et en radiothérapie. Ce système a été installé dans la clinique et utilisé par trois patients pendant la radiothérapie et une quinzaine de patients pendant des simulations CTs. Il a ainsi été observé que l’utilisation du « feedback » permettait de régulariser la respiration des patients et ainsi d’optimiser l’utilisation des techniques de « gating » afin de réduire l’effet des mouvements interne des tumeurs durant la thérapie et les simulations. La deuxième partie de l’enquête consistait en une étude retrospective qui avait pour but de permettre la comparaison de plusieurs algorithmes de calcul de dose. Les résultats obtenus à l’aide des algorithmes du système de planification de traitements Eclipse ont été comparés à ceux qui ont été calculés en utilisant les codes Monte Carlos EGSnrc et DOSXYZnrc. Les données de quatre patients souffrant du cancer du poumon qui avaient étés traités avec des faisceaux de photons 18 MV ont ainsi été recalculées. Les résultats obtenus ont démontré que les algorithmes d’Eclipse surestimaient systématiquement les doses à cause de la faible densité des tissus pulmonaires et du manque d’équilibre électronique dû au dimensions des faisceaux.

La radioterapia è una tecnica molto impiegata per la cura del cancro. Attualmente la somministrazione avviene principalmente attraverso la intensity modulated radiotherapy (IMRT, sovrapposizione di campi ad intensità modulata), un cui sviluppo recente è la volumetric modulated arc therapy (VMAT, irradiazione continua lungo un arco ininterrotto). La generazione di piani richiede esperienza ed abilità: un dosimetrista seleziona cost functions ed obiettivi ed un TPS ottimizza la disposizione dei segmenti ad intensità modulata. Se il medico giudica il risultato non soddisfacente, il processo riparte da capo (trial-and-error). Una alternativa è la generazione automatica di piani. Erasmus-iCycle, software prodotto presso ErasmusMC (Rotterdam, The Netherlands), è un algoritmo di ottimizzazione multicriteriale di piani radioterapici per ottimizzazione di intensità basato su una wish list. L'output consiste di piani Pareto-ottimali ad intensità modulata. La generazione automatica garantisce maggiore coerenza e qualità più elevata con tempi di lavoro ridotti. Nello studio, una procedura di generazione automatica di piani con modalità VMAT è stata sviluppata e valutata per carcinoma polmonare. Una wish list è stata generata attraverso una procedura iterativa su un gruppo ristretto di pazienti con la collaborazione di fisici medici ed oncologi e poi validata su un gruppo più ampio di pazienti. Nella grande maggioranza dei casi, i piani automatici sono stati giudicati dagli oncologi migliori rispetto ai rispettivi piani IMRT clinici generati manualmente. Solo in pochi casi una rapida calibrazione manuale specifica per il paziente si è resa necessaria per soddisfare tutti i requisiti clinici. Per un sottogruppo di pazienti si è mostrato che la qualità dei piani VMAT automatici era equivalente o superiore rispetto ai piani VMAT generati manualmente da un dosimetrista esperto. Complessivamente, si è dimostrata la possibilità di generare piani radioterapici VMAT ad alta qualità automaticamente, con interazione umana minima. L'introduzione clinica della procedura automatica presso ErasmusMC è iniziata (ottobre 2015).

Lung cancer is the leading cause of cancer-related deaths worldwide. Radiotherapy is one of the main treatment modalities of lung cancer. However, the achievable accuracy of radiotherapy treatment is limited for lung-based tumors due to respiratory motion. Four-dimensional radiotherapy explicitly accounts for anatomic motion by characterizing the motion, creating a treatment plan that accounts for this motion, and delivering this plan to the moving anatomy. This thesis focuses on the current problems and solutions throughout the course of four-dimensional radiotherapy. For characterization of respiratory-induced motion, patient tumor motion data were analyzed. It is shown that tumor motion can be significant during radiotherapy treatment, and its extent, direction, and linearity vary considerably between patients, between treatment fractions, and between respiratory cycles. After this, approaches to four-dimensional intensity-modulated radiation therapy treatment planning were developed and investigated. Among the techniques to manage respiratory motion, tumor tracking using a dynamic multileaf collimator delivery technique was chosen as a promising method. A formalism to solve a general four-dimensional intensity-modulated radiation therapy treatment-planning problem was developed. Specific solutions to this problem accounting for tumor motion initially in one dimension and extending this to three dimensions were developed and investigated using four-dimensional computed tomography planning scans of lung cancer patients. For four-dimensional radiotherapy treatment delivery, accuracy of two-dimensional projection imaging methods was investigated. Geometric uncertainty due to the limitation of two-dimensional imaging in monitoring three-dimensional tumor motion during treatment delivery was quantified. This geometric uncertainty can be used to estimate proper margins when a single two-dimensional projection imager is used for four-dimensional treatment delivery. Lastly, tumor-tracking delivery using a moving average algorithm was investigated as an alternative delivery technique that reduces mechanical motion constraints of a multileaf collimator. Moving average tracking provides an approximate solution that can be immediately implemented for delivery of four-dimensional intensity-modulated radiation therapy treatment. The clinical implementation of four-dimensional guidance, intensity-modulated radiation therapy treatment planning, and dynamic multileaf collimator tracking delivery may have a positive impact on the treatment of lung cancer.

The radiotherapy clinics in Sweden have been without a functioning national platform consisting of dose data from patients undergoing radiotherapy. A national collaboration between clinics will improve the quality of radiotherapy since clinics will be able to compare dose data from treatment plans between clinics. It will also help and improve future researches in radiotherapy. A new national quality registry for radiotherapy in Sweden is under development and is located on the INCA platform. The aim of this study is to do a quality assurance of the INCA registry. The data stored in the registry are calculated from the treatment plans stored locally at the clinics. The quality assurance of the registry is done by creating a program run by Python code and by using Streamlit as the graphical user interface. The program takes dose and volume data from the dose volume histograms located in treatment plans from the INCA database and compares it with the dose and volume data from the local clinics' treatment planning system. The different treatment planning systems considered in the program are Oncentra(Elekta, Sweden), Eclipse(Varian, U.S.), RayStation(RaySearch Laboratories, Sweden) and Monaco(Electa, Sweden). The compared absorbed doses are the dose to 99% of the structure volume(D99%), D98%, D50%, D2% and D1%. The program generates how much the INCA data differs from the TPS data in percent and is named QARS(Quality Assurance of the Radiotherapy Database in Sweden). A verification of the created program and a preliminary evaluation is done on a limited dataset containing three patient groups(prostate patients, lung patients and head and neck patients) with five patients in each group. The dataset is run through the program with patient data from both Oncentra and Eclipse. The result indicates that all the near-maximum doses, D2% and D1% in INCA are very close to their corresponding TPS dose. There is a more noticeable difference in the near-minimum doses, D99% and D98% but also for some D50% where the difference seems to increase in larger structure volumes with very low doses and in very small structure volumes, smaller than 0.01 cm3. It is compared how well INCA agrees with Oncentra and Eclipse respectively and it is clear that Eclipse has a smaller difference to INCA than Oncentra for structures with very small volumes and larger structures with low doses. To summarise the study, it generates a program for quality assurance of the national quality registry for radiotherapy in Sweden which hopefully can help improve the quality of radiotherapy and help future researches in the field.

The flattening filter is a conical shaped piece of metal sitting within the treatment head of a linear accelerator, used to produce a flat, uniform beam of X-rays from the forward-peaked distribution exiting the target. Despite their routine use since the introduction of the linac in the 1950’s, however, there are still several unresolved issues surrounding their use. The photon scatter and electron contamination introduced by modifying the fluence are difficult to model, as is the variation in energy spectrum caused by differential absorption across the field. Leakage radiation also causes increased whole body doses to the patient, and the filter itself causes acts as an amplifier for beam bending and steering issues. With advances in tumour imaging, dose optimisation and in-room image-guidance it is now possible to locate a tumour accurately in space and to design radiation fields to conform to its shape, avoiding adjacent normal and critical tissues. This active production of non-flat fields means that the prerequisite for flat fields no longer exists, and the filter is potentially no longer a necessary component. This thesis reports on research to produce a filter-free linear accelerator, from basic operation and optimisation, dosimetric characterisation and beam modelling, through to treatment planning and dose delivery. FFF beams have been shown reduce many of the problems seen with the current generation of linear accelerators, producing beams that are inherently more stable, simple to model and with reduced patient leakage (leading to reduced secondary cancers). The increase in dose rate also translates into shorter treatment times for many treatments, aiding patient comfort and reducing problems associated with intra-fraction motion.

There has been an increasing interest in proton beam therapy (PBT) in recent years related to the advantageous depth-dose characteristics of proton beams compared to what is achievable with standard external photon beam radiotherapy (RT). With PBT, improved target dose conformity can be achieved together with a reduction in the dose to the organs at risk (OARs). This can for certain cases lead to an increased tumour control probability (TCP) at the same time as the probabilities for normal tissue complications (NTCP) and radiation-induced secondary cancers are reduced. However, there are challenges with PBT, in the form of uncertainties in the dose delivery to the patient, due to different influencing factors. These perturbing factors are contributing to the uncertainties during different steps in the RT flow process, from the treatment planning to the irradiation. In the present work, a comparative treatment planning study of PBT and photon RT for a few clinical liver- and stomach-cancer cases were performed with the aim of determining possible advantages of PBT. The treatment planning comparisons were performed by means of dosimetric evaluations and by use of tissue response models. The later included the calculation of TCP and NTCP as well as the assessment of risk of radiation-induced secondary cancer for the two compared RT techniques. A total of eleven patients previously treated with RT at Karolinska University Hospital were included in the study. Three of these patients had been treated for liver cancer and eight for stomach cancer. The photon plans which had been used in the real treatments at the hospital were taken as reference plans. The treatment planning for the liver cancer cases had been performed on conventional CT images, but 4D-CT images were used for target definition to account for the target motion.  Three distinct CT images were used in the planning of the stomach cancer cases, the original CT image study on which the photon plans had been done and two CT image studies with artificially changed physical density for some of the internal organs to simulate different possible fillings of the stomach. The extra- or reduced gas filling was drawn on the CT slices by the radiation oncologist to estimate two worst-case scenarios for changes in density within the irradiated volume. The results indicate an improved target dose conformity, dose homogeneity and sparing of OARs for the PBT plans compared to the photon RT plans for the two clinical cases studied. The sparing of the OARs was also observed in the form of decreased NTCP for the PBT plans. The PBT plans showed to be worse than the photon plans when some structures were replaced by air and water. In the case of extra air there was a shift of the higher doses beyond the distal edge of the planned proton range which caused both an increase of the irradiated volumes of sensitive normal tissues and of the maximum doses to the OARs. In the case of extra water in the stomach, the maximum range of the protons was reduced causing target underdosage.  The calculations of probabilities for radiation-induced secondary malignancies indicated a reduced risk for all the OARs with the proton plans for the liver cancer cases. For the stomach cancer cases, reduced risks were obtained for induction of cancer in the liver but an increased risk was calculated for the bowel(-)PTV, with the proton- compared to the photon-plans. The results of the calculations of risk for radiation-induced cancer in the kidneys were inconclusive. The assessment of risk of secondary cancer for other organs, not delineated in this work (to obtain the whole body risk), is needed in order to obtain more comprehensive and clinically useful results.

La radiothérapie externe est un traitement locorégional du cancer. L’objectif de la radiothérapie impose un compromis entre la délivrance d’une dose maximale dans la tumeur afin d’augmenter le contrôle local et la curabilité, et d’une dose minimale aux organes sains afin de limiter la toxicité. Les symptômes urinaires peuvent être liés à l’irradiation de régions spécifiques de la vessie ou de l'urètre. Dans ce cas, la dose reçue par l'ensemble de la vessie peut ne pas suffire à expliquer la toxicité urinaire. Dans le contexte du traitement du cancer de la prostate par radiothérapie, ce travail de thèse vise à analyser les corrélations spatiales entre la dose et les effets secondaires, cette problématique étant abordée dans un cadre d'analyse de population. Pour évaluer la contribution de l'urètre à la toxicité urinaire, nous proposons une méthode de segmentation basée sur plusieurs atlas pour identifier avec précision cette structure sur les images CT. Nous utilisons ensuite deux méthodes pour analyser la distribution de dose spatiale. L'une basée sur la construction de cartes 2D dose-surface (DSM) couplée à des comparaisons pixel par pixel et l'autre basée sur des cartes 3D dose-volume (DVM) combinées à des comparaisons par voxel. Les sous-régions identifiées ont été validées dans des populations externes, ouvrant la perspective d'une planification de traitement spécifique du patient. Nous étudions également le potentiel d'une amélioration complémentaire de la prédiction en exploitant de méthodes d'apprentissage automatique
External beam radiotherapy (EBRT) is a clinical standard for treating prostate cancer. The objective of EBRT is to deliver a high radiation dose to the tumor to maximize the probability of local control while sparing the neighboring organs (mainly the rectum and the bladder) in order to minimize the risk of complications. Developing reliable predictive models of genitourinary (GU) toxicity is of paramount importance to prevent radiation-induced side-effects, and improve treatment reliability. Urinary symptoms may be linked to the irradiation of specific regions of the bladder or the urethra, in which case the dose received by the entire bladder may not be sufficient to explain GU toxicity. Going beyond the global, whole-organ-based models towards more local, sub-organ approaches, this thesis aims to improve our understanding of radiation-induced urinary side-effects and ameliorate the prediction of urinary toxicity following prostate cancer radiotherapy. With the objective to assess the contribution of urethra damage to urinary toxicity, we propose a multi-atlas-based segmentation method to accurately identify this structure on CT images. The second objective is to identify specific symptom-related subregions in the bladder and the urethra predictive of different urinary symptoms. For this purpose, we propose two methodologies for analyzing the spatial dose distribution; one based on the construction of 2D dose-surface maps (DSM) coupled with pixel wise comparisons and another based on 3D dosevolume maps (DVMs) combined with voxel-wise comparisons. Identified subregions are validated in external populations, opening the perspective for patient specific treatment planning. We also implement and compare different machine learning strategies and data augmentation techniques, paving the way to further improve urinary toxicity prediction. We open the perspective of patient-specific treatment planning with reduced risk of complications

Aims: To develop clinical protocols for acquiring PET images, performing CT-PET registration and tumour volume definition based on the PET image data, for radiotherapy for lung cancer patients and then to test these protocols with respect to levels of accuracy and reproducibility. Method: A phantom-based quality assurance study of the processes associated with using registered CT and PET scans for tumour volume definition was conducted to: (1) investigate image acquisition and manipulation techniques for registering and contouring CT and PET images in a radiotherapy treatment planning system, and (2) determine technology-based errors in the registration and contouring processes. The outcomes of the phantom image based quality assurance study were used to determine clinical protocols. Protocols were developed for (1) acquiring patient PET image data for incorporation into the 3DCRT process, particularly for ensuring that the patient is positioned in their treatment position; (2) CT-PET image registration techniques and (3) GTV definition using the PET image data. The developed clinical protocols were tested using retrospective clinical trials to assess levels of inter-user variability which may be attributed to the use of these protocols. A Siemens Somatom Open Sensation 20 slice CT scanner and a Philips Allegro stand-alone PET scanner were used to acquire the images for this research. The Philips Pinnacle3 treatment planning system was used to perform the image registration and contouring of the CT and PET images. Results: Both the attenuation-corrected and transmission images obtained from standard whole-body PET staging clinical scanning protocols were acquired and imported into the treatment planning system for the phantom-based quality assurance study. Protocols for manipulating the PET images in the treatment planning system, particularly for quantifying uptake in volumes of interest and window levels for accurate geometric visualisation were determined. The automatic registration algorithms were found to have sub-voxel levels of accuracy, with transmission scan-based CT-PET registration more accurate than emission scan-based registration of the phantom images. Respiration induced image artifacts were not found to influence registration accuracy while inadequate pre-registration over-lap of the CT and PET images was found to result in large registration errors. A threshold value based on a percentage of the maximum uptake within a volume of interest was found to accurately contour the different features of the phantom despite the lower spatial resolution of the PET images. Appropriate selection of the threshold value is dependant on target-to-background ratios and the presence of respiratory motion. The results from the phantom-based study were used to design, implement and test clinical CT-PET fusion protocols. The patient PET image acquisition protocols enabled patients to be successfully identified and positioned in their radiotherapy treatment position during the acquisition of their whole-body PET staging scan. While automatic registration techniques were found to reduce inter-user variation compared to manual techniques, there was no significant difference in the registration outcomes for transmission or emission scan-based registration of the patient images, using the protocol. Tumour volumes contoured on registered patient CT-PET images using the tested threshold values and viewing windows determined from the phantom study, demonstrated less inter-user variation for the primary tumour volume contours than those contoured using only the patient’s planning CT scans. Conclusions: The developed clinical protocols allow a patient’s whole-body PET staging scan to be incorporated, manipulated and quantified in the treatment planning process to improve the accuracy of gross tumour volume localisation in 3D conformal radiotherapy for lung cancer. Image registration protocols which factor in potential software-based errors combined with adequate user training are recommended to increase the accuracy and reproducibility of registration outcomes. A semi-automated adaptive threshold contouring technique incorporating a PET windowing protocol, accurately defines the geometric edge of a tumour volume using PET image data from a stand alone PET scanner, including 4D target volumes.

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O presente estudo consiste na análise da viabilidade econômica e financeira da implantação da radioterapia de intensidade modulada (IMRT) no tratamento do câncer de próstata e comparar seus benefícios clínicos frente aos procedimentos similares custeados pelos sistemas de saúde públicos e privados. Para tanto, foram analisadas as distribuições de dose de radiação preconizadas nos planejamentos radioterápicos com as técnicas de radioterapia conformacional tridimensional (3D-CRT) e de intensidade modulada (IMRT), prescrita para 20 pacientes com câncer de próstata tratados em um serviço de radioterapia privado. Para verificação da qualidade da distribuição de dose de radiação no volume de tratamento, foram analisados os índices de homogeneidade (IH) e de conformidade (IC) de cada um dos planos radioterápicos estudados. Em comparação com a técnica 3D-CRT, a técnica de IMRT permitiu uma melhor cobertura e conformação da dose prescrita no volume alvo de planejamento (PTV), porém distribuída de forma mais heterogênea. Além disso, avaliou-se os custos financeiros para aquisição dos equipamentos de irradiação e manutenção dos tratamentos, bem como os valores de repasses feitos pelos sistemas de saúde para os procedimentos de radioterapia em próstata.
The present study consists in analyzing the economic and financial viability to establish the intensity modulated radiotherapy (IMRT) in the treatment for prostate cancer and compare its clinical benefits to similar procedures funded by public and private health systems. In order to do so, the radiation absorbed-dose distributions recommended in the radiotherapy plans with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques, prescribed for 20 patients with prostate cancer treated in a private radiotherapy clinic, were evaluated. To verify the quality of the radiation dose distribution in the treatment volume, the homogeneity index (HI) and the conformity index (CI) of each radiotherapy plans studied were analyzed. In contrast to the 3D-CRT technique, the IMRT technique allowed a better coverage and conformation of the radiation dose prescribed in the planning target volume (PTV), but distributed in a more heterogeneous way. It was also evaluated the financial costs for the acquisition of the irradiation equipment and for the maintenance of the treatments, as well as the values of the on-lending made by the health systems for the radiotherapy procedures for the prostate.

Orientador: Marco Antônio Rodrigues Fernandes
Resumo: O presente estudo consiste na análise da viabilidade econômica e financeira da implantação da radioterapia de intensidade modulada (IMRT) no tratamento do câncer de próstata e comparar seus benefícios clínicos frente aos procedimentos similares custeados pelos sistemas de saúde públicos e privados. Para tanto, foram analisadas as distribuições de dose de radiação preconizadas nos planejamentos radioterápicos com as técnicas de radioterapia conformacional tridimensional (3D-CRT) e de intensidade modulada (IMRT), prescrita para 20 pacientes com câncer de próstata tratados em um serviço de radioterapia privado. Para verificação da qualidade da distribuição de dose de radiação no volume de tratamento, foram analisados os índices de homogeneidade (IH) e de conformidade (IC) de cada um dos planos radioterápicos estudados. Em comparação com a técnica 3D-CRT, a técnica de IMRT permitiu uma melhor cobertura e conformação da dose prescrita no volume alvo de planejamento (PTV), porém distribuída de forma mais heterogênea. Além disso, avaliou-se os custos financeiros para aquisição dos equipamentos de irradiação e manutenção dos tratamentos, bem como os valores de repasses feitos pelos sistemas de saúde para os procedimentos de radioterapia em próstata.
Mestre

OBJETIVOS: Verificar o índice de erros geográficos no planejamento radioterápico convencional de pacientes com carcinoma de colo uterino por meio da ressonância magnética (RM); comparar os dados de estadiamento da FIGO pelos exames físico e de RM e avaliar o estudo do Raio-X contrastado de reto na previsão do erro geográfico. MATERIAIS E MÉTODOS: Oitenta pacientes com diagnóstico histológico de carcinoma espinocelular de colo uterino, com indicação de radioterapia, foram analisadas. Após o estadiamento clínico (FIGO), foi realizada ressonância magnética da pelve e estas imagens comparadas aos campos clássicos de radioterapia, técnica de 4 campos em tijolo. Considerou-se erro geográfico, quando o volume alvo não foi englobado pelos campos, com margens mínimas de 1cm. Os dados de exame físico e RM foram comparados. RESULTADOS: Entre as 80 pacientes analisadas, os limites clássicos dos campos não foram adequados em 45 (56%). Os limites críticos foram as bordas anterior (1/3 anterior da sínfise púbica) ou posterior (limite em S2-S3) dos campos laterais de irradiação. Evidenciou-se grande discrepância entre o exame físico e a RM no que se refere à análise de informações para o estadiamento. Na maioria das vezes, o exame físico sub-estadiou as lesões, principalmente na detecção de doença vaginal e parametrial. Lesões com diâmetro antero-posterior maior que 6cm e volume acima de 100cm3 apresentaram correlação estatisticamente significante com o erro geográfico. O posicionamento da parede anterior do reto fora do limite posterior dos campos laterais, no raio-X contrastado mostrou correlação estatisticamente significante com o erro geográfico. CONCLUSÕES: Em relação aos limites dos campos de irradiação a RM foi decisória para adequação dos campos de radioterapia, na maioria das pacientes. O estadiamento por RM, comparado ao exame físico, mostrou-se preciso na avaliação de volume tumoral e extensão da doença. No presente estudo, a avaliação do deslocamento da parede anterior do reto na radiografia dos campos laterais de irradiação mostrou associação com o risco de erro geográfico.
OBJECTIVES The purposes of this study were to verify the chances of geographic miss in conventional 2-dimensional radiotherapy planning in patients with uterine cervix cancer, by means of magnetic resonance imaging (MRI); to compare the data from FIGO staging system with MRI findings; and to evaluate the influence of contrasted rectum X-ray in predicting geographic miss. MATERIAL AND METHODS: Eighty patients with uterine cervical carcinoma were analyzed. After clinical staging (FIGO), magnetic resonance imaging of the pelvis was performed. The images were compared to the classic 4-field technique (box) of radiotherapy. Geographic miss was considered when the tumor volume was not included in the irradiation fields with at least 1cm margins. Data of physical examination and RM were compared. RESULTS: In 45 (56,2%) of the 80 studied patients, fields? limits were not adequate. The anterior (anterior 1/3 of pubis) and posterior limits (S2-S3) of the lateral fields of irradiation were critical. Great discrepancy was observed when physical exam was compared to MRI findings. In most cases, physical exam tended to under-stage the tumors, mainly due to vaginal and parametrial extension. Tumors with antero-posterior diameter larger than 6cm and volume above 100cm3 presented statistically significant correlation with geographical miss. Displacement of the anterior rectal wall outside the posterior limit of the lateral fields in the contrasted X-ray was also significantly correlated with geographical miss. CONCLUSIONS: MRI findings detected and prevented geographic misses in the majority of the patients. When compared to physical examination, tumor volume and extension were better defined by MRI. In the present study, the evaluation of the anterior rectal wall displacement in the lateral x-ray of the irradiation fields was associated with the risk of geographical miss.

Au-delà des techniques conventionnelles de diagnostic et de suivi du cancer, l’analyse radiomique a pour objectif de permettre une médecine plus personnalisée dans le domaine de la radiothérapie, en proposant une caractérisation non invasive de l’hétérogénéité tumorale. Basée sur l’extraction de paramètres quantitatifs avancés (histogrammes des intensités, texture, forme) issus de l’imagerie multimodale, cette technique a notamment prouvé son intérêt pour définir des signatures prédictives de la réponse aux traitements. Dans le cadre de cette thèse, des signatures de la récidive des cancers du col utérin ont notamment été développées, à partir de l’analyse radiomique seule ou en combinaison avec des biomarqueurs conventionnels, apportant des perspectives majeures dans la stratification des patients pouvant aboutir à une adaptation spécifique de la dosimétrie.En parallèle de ces études cliniques, différentes barrières méthodologiques ont été soulevées, notamment liées à la grande variabilité des protocoles et technologies d’acquisition des images, qui entraîne un biais majeur dans les études radiomiques multicentriques. Ces biais ont été évalués grâce à des images de fantômes et des images multicentriques de patients pour l’imagerie TEP, et deux méthodes de correction de l’effet de stratification ont été proposées. En IRM, une méthode de standardisation des images par harmonisation des histogrammes a été évaluée dans les tumeurs cérébrales.Pour aller plus loin dans la caractérisation de l’hétérogénéité intra-tumorale et permettre la mise en œuvre d’une radiothérapie personnalisée, une méthode d’analyse locale de la texture a été développée. Adaptée particulièrement aux images IRM de tumeurs cérébrales, ses capacités à différencier des sous-régions de radionécrose ou de récidive tumorale ont été évaluées. Dans ce but, les cartes paramétriques d’hétérogénéité ont été proposées à des experts comme des séquences IRM additionnelles.À l’issue de ce travail, une validation dans des centres extérieurs des modèles développés, ainsi que la mise en place d’essais cliniques intégrant ces méthodes pour personnaliser les traitements seront des étapes majeures dans l’intégration de l’analyse radiomique en routine clinique
Beyond the conventional techniques of diagnosis and follow-up of cancer, radiomic analysis allows to personalize radiotherapy treatments, by proposing a non-invasive characterization of tumor heterogeneity. Based on the extraction of advanced quantitative parameters (histograms of intensities, texture, shape) from multimodal imaging, this technique has notably proved its interest in determining predictive signatures of treatment response. During this thesis, signatures of cervical cancer recurrence have been developed, based on radiomic analysis alone or in combination with conventional biomarkers, providing major perspectives in the stratification of patients that can lead to dosimetric treatment plan adaptation.However, various methodological barriers were raised, notably related to the great variability of the protocols and technologies of image acquisition, which leads to major biases in multicentric radiomic studies. These biases were assessed using phantom acquisitions and multicenter patient images for PET imaging, and two methods enabling a correction of the stratification effect were proposed. In MRI, a method of standardization of images by harmonization of histograms has been evaluated in brain tumors.To go further in the characterization of intra-tumor heterogeneity and to allow the implementation of a personalized radiotherapy, a method for local texture analysis has been developed. Specifically adapted to brain MRI, its ability to differentiate sub-regions of radionecrosis or tumor recurrence was evaluated. For this purpose, parametric heterogeneity maps have been proposed to experts as additional MRI sequences.In the future, validation of the predictive models in external centers, as well as the establishment of clinical trials integrating these methods to personalize radiotherapy treatments, will be mandatory steps for the integration of radiomic in the clinical routine

碩士
中國醫藥大學
生物醫學影像暨放射科學學系碩士班
105
Radiotherapy is currently one of the main treatment of the cancer. In order to avoid the normal tissue to accept too much radiation, the radiotherapy treatment planning will be designed before clinical radiation therapy. The Radiotherapy treatment planning is usually performed by experienced radiophysicists and oncologists, who are according to personal experience and imaging information, routinely contour organs near the tumor and the treatment range, and this process usually spends a lot of time. We believe that the contours of the organ can be obtained by the result of image segmentation, and if reducing the time of the contouring process during designing the radiotherapy treatment planning can increase the efficiency and reduce the human consumption. We used the random walks algorithm to segment the image, and built a graphical user interface system to assist the user to set seed points, using the random walks algorithm for image segmentation obtained organ contours through the seed points are provided by the user. We contoured the lungs, trachea, heart, spinal cord, body and target tumor volume in the experiment, and compared with the contours of the experts. In our experimental results, the most of the results of each organ in contour cases and clinical cases were good, only slightly higher in the volume of the spinal cord. In the results of the calculus, the average amount of time spent in each study in our study was about two minutes, and it was effectively to save time.

PURPOSE: To demonstrate the feasibility of using a knowledge base of prior treatment plans to generate new prostate intensity modulated radiation therapy (IMRT) plans. Each new case would be matched against others in the knowledge base. Once the best match is identified, that clinically approved plan is used to generate the new plan. METHODS: A database of 100 prostate IMRT treatment plans was assembled into an information-theoretic system. An algorithm based on mutual information was implemented to identify similar patient cases by matching 2D beam's eye view projections of contours. Ten randomly selected query cases were each matched with the most similar case from the database of prior clinically approved plans. Treatment parameters from the matched case were used to develop new treatment plans. A comparison of the differences in the dose-volume histograms between the new and the original treatment plans were analyzed. RESULTS: On average, the new knowledge-based plan is capable of achieving very comparable planning target volume coverage as the original plan, to within 2% as evaluated for D98, D95, and D1. Similarly, the dose to the rectum and dose to the bladder are also comparable to the original plan. For the rectum, the mean and standard deviation of the dose percentage differences for D20, D30, and D50 are 1.8% +/- 8.5%, -2.5% +/- 13.9%, and -13.9% +/- 23.6%, respectively. For the bladder, the mean and standard deviation of the dose percentage differences for D20, D30, and D50 are -5.9% +/- 10.8%, -12.2% +/- 14.6%, and -24.9% +/- 21.2%, respectively. A negative percentage difference indicates that the new plan has greater dose sparing as compared to the original plan. CONCLUSIONS: The authors demonstrate a knowledge-based approach of using prior clinically approved treatment plans to generate clinically acceptable treatment plans of high quality. This semiautomated approach has the potential to improve the efficiency of the treatment planning process while ensuring that high quality plans are developed.
Dissertation

Advanced-stage nasopharyngeal carcinoma (NPC) presents very difficult scenarios for radiation therapy (RT) planning. The infiltration of tumor to the skull base and beyond means that the tumor is very close to critical normal organs (organs at risk, OARs). Despite the advent of intensity-modulated radiotherapy (IMRT) treatment technique---the state-of-art RT technique, conflicting requirements between organ protection and target dose conformity is still problematic. The objectives of the present research are (1) to investigate the dosimetry properties of IMRT treatment in advanced-stage NPC in respect of its dosimetric limitations and planning problems, (2) to develop new methods and tools to resolve such problems, in particular to improve the quality of treatment plans and efficiency of the dose planning and optimization process. A series of four inter-linked studies were conducted to address these issues.
In conclusion, the solutions to several major problems in IMRT planning for advanced-stage NPC were investigated and established. It has been demonstrated in this research that, by applying these methods and tools, significant improvement in the dosimetry and efficiency of IMRT treatment planning can be accomplished as compared with conventional IMRT planning techniques. It is expected that such would translate into an improvement in treatment throughput, better tumor control and reduction in normal tissues complications. The methods developed have potential to be applied to all stages of NPC and to other tumor sites.
The first study was to improve the efficacy in target coverage and organs sparing using an "organ-splitting" approach. The OARs which overlapped with targets were split into target-overlapping and non-overlapping segments and each segment was assigned with different constraints parameters to increase the degree of flexibility during optimization. As a result, a steep gradient in the dose distribution at the regions of interface between the targets and normal critical organs could be achieved and treatment quality was improved. In the second study, a thorough dosimetric comparison between conventional 2-dimensional (2D) RT and IMRT plans was conducted to determine, with reference to outcome of 2D treatments, the extended tolerance dose limits for the critical organs, especially that of the brainstem and spinal cord, and their planning organ at risk volume. Such data could then serve as reference in IMRT planning when the dose of critical organs need be exceeded in order to allow adequate dose to a very close by target. In the third study, the feasibility of using interpolated contours for segmentation of targets and OARs in IMRT planning was investigated. The result indicated that the use of interpolated contours in IMRT planning could significantly reduce the contouring time by about 50% without degrading the target coverage and OARS sparing. In the final study, an array of dose constraint templates that could accommodate different degrees of overlap between the targets and OARs, together with a template selection program, were developed to improve the efficiency of IMRT planning. By applying the methods and tools developed, IMRT treatment planning of advanced NPC could become more efficient and less dependent on planner's experience.
Chau, Ming Chun.
Adviser: Anthony Chan Tak Cheung.
Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0948.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2007.
Includes bibliographical references (leaves 118-128).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
School code: 1307.

碩士
國立高雄應用科技大學
電子工程系碩士班
104
Purpose: Currently, analysis of second cancer risk (SCR) induced radiation dose in radiotherapy is quite important but is also not convenient. This study develops a quick, convenient, simple analysis platform of SCR with the models of risk analysis. Materials and methods: In this study, the graphical user interface (GUI) in Matlab and risk equivalent dose (RED) response curve published Schneider et al. in 2011 are used to develop the user-friendly operating platform. According to fractionation effects and cell repopulation, RED response curve can be divided into linear model, linear-exponential model and plateau model. Three models calculate individual organ equivalent dose (OED), and estimate excess absolute risk (EAR) and lifetime attributable risk (LAR). The RANDO phantoms of whole body irradiation are used to simulation analysis the therapy-induced second cancer risks of breast cancer of female and nasopharyngeal cancer of male. Results: In the present study, SCR of platform designs graphical buttons to operate easily for users. In order to operate fast and simply, functions of platform are data loading, input of basic information (age, sex, organ, classification of tissues, etc.), estimation of risks of second cancer and output of result. Because supporting windows operating system, the system of SCR can be popularly applied to the general computers, and can be used to enhance convenience of research in future. Besides, the simulation results of EAR of patients of ipsilateral breast are 183.11, 43.52 and 50.71 people per million in linear model, linear-exponential model and plateau model, respectively. In the simulation results of patients of nasopharyngeal cancers, the EAR of second cancers induced in different organs are ten or less people per ten million in linear-exponential model and plateau model except the overestimation of linear model is potential. Conclusions: This study develops a fast, convenient, simple-operated platform which analyzes probability of second cancers. Not only can doctors and researchers use it and the dose-volume histogram (DVH) provided by treatment systems of hospitals to estimate the excess absolute risk (EAR) and lifetime attributable risk (LAR), but they also make treatment plans of patients perfect. Finally, patient’s the quality of life (QoL) can be improved by this platform.

Research Doctorate - Doctor of Philosophy (PhD)
Radiotherapy is one of the main methods used to treat prostate cancer. Radiotherapy treatment relies on accurate planning and simulation before any radiation is administered. Currently this is mainly based on CT (computed tomography) imaging, although MR (magnetic resonance) imaging provides superior soft-tissue contrast and is therefore often used to assist with accurate organ delineation. The overall treatment planning workflow and performance can be improved if the entire workflow is solely performed using MR images. In order to achieve such MR-only treatment planning, three main challenges need to be overcome: 1) the geometric accuracy of MR images needs to be assured ; 2) the MR simulator needs to be commissioned and evaluated ; 3) electron density information required for dose calculation needs to be generated from MR images. This thesis examines each of these challenges. First, a pelvic shape phantom was used to quantify the geometric distortion arising in prostate treatment. The CT image was acquired as the gold reference and the distortion of the MR image was corrected with the vendor’s built-in algorithm. Using the image registration method, the maximum geometric distortion was reduced from nearly 8 mm to within the radiotherapy tolerance level. Second, commercial radiotherapy-dedicated equipment was implemented on the Siemens Skyra 3 Tesla MR scanner. This involved a hard flat tabletop which mimicked the flat radiotherapy treatment table, and coil mounts to lift the MR coil above the patient’s body and minimise coil-induced disagreement between the MR planning and treatment geometry. A reduction in image quality was observed on the MR simulator, but no clinically significant difference was found in the accuracy of organ delineation. Furthermore, use of the MR simulator eliminated patient positioning error associated with conventional MR scanner design and thus reduced the systematic dosimetric error. The entire workflow of MR-based planning was tested using an anthropomorphic phantom and no significant difference was found between MR- and CT-based plans. Finally, substitute (also known as synthetic or pseudo) sCT images were generated from MR images using a multi-atlas local weighted voting method. Validation was conducted on 39 patients and the sCT images were in high level agreement with the CT images. In summary, MR-based radiotherapy planning for treating prostate cancer has been thoroughly tested and evaluated in this study. This may provide an important stepping stone for the future clinical implementation.

碩士
長庚大學
醫學影像暨放射科學系
101
With advances of modern radiotherapy techniques, effectiveness of radiation therapy is receiving wide attention. Seven postoperative oral cancer patients were enrolled into this study to explore dose variation due to weekly organ volume change under fractionated treatment scheme. The study also evaluated weekly treatment plans under the adaptive IMRT and the RapidArc re-planning protocols. An initial treatment plan generated using the pre-treatment CT image set of a patient was re-assigned to the sequential weekly CT image sets for dose recalculation, to evaluate dose differences between the planned and presumedly delivered dose distributions. In addition, adaptive weekly IMRT and RapidArc plans on the weekly CT image sets were performed. Consequently, dose differences between the existing treatment protocoland the adaptive re-planning protocols were evaluated. Results showed that no matter for the existing or the adaptive treatment protocols, their weekly CTV target doses did not result in significant difference. For the existing treatment protocol, weekly doses to critical organs such as the brain stem, spinal cord and parotid glands increased significantly. This dose increases can be improved to within the dose tolerance levels with the adaptive re-planning strategy. Finally, due to the small number of study subjects, no statistical evaluation is attempted.

碩士
元培醫事科技大學
醫學影像暨放射技術系碩士班
107
Abstract Purpose: Nowadays, radiation therapy comes to the standard treatment for prostate cancer. There are many critical Organ at Risks (OARs) can be affected during and after the treatment, which can negatively affect patients’ later life. In our study, we made comparisons in terms of the optimal dose to target as well as sparing dose to OARs among three techniques 3D-CRT, IMRT and VMAT in late stage (T3, T4) of prostate cancer. Materials and Methods: Ten late-stages (T3-T4) of prostate cancer patients after being treated by IMRT 5-7 fields were recruited and their CT simulation data formed two more planning: 3D-CRT and VMAT technique. Treatment plan system is Philips Healthcare. The dose influence in PTV was evaluated by Homogeneity index (HI) and Conformation index (CI). Simultaneously, we compared the dose in OARs among three planning methods. All data analyzed with SPSS version 20 by Paired samples T-test to find the statistical significance of each factor. Results: Three treatment planning met the target coverage (over 95% prescription) and dose distribution. However, IMRT and VMAT showed the optimal dose in mean dose in the target, p<0.05. Besides, distribution dose in OARs of IMRT and VMAT was significantly lower comparing with 3D-CRT planning, p<0.05. MU of IMRT (793.4±37.2) planning illustrated higher than 3D-CRT (305.5±19.80) and VMAT (483.8±21.3). VMAT planning was successful in reducing MU and treatment time. Conclusion: Our study demonstrated that VMAT planning was significantly better in planning quality compared with 3D-CRT and IMRT in the optimal dose to target, OARs and treatment time. Keywords: PTV, OARs, Prostate cancer, Dosimitry, 3D-CRT, IMRT and VMAT.

碩士
中國醫藥大學
臨床醫學研究所碩士班
99
Purpose: Studies suggested PET overlay on CT has shown to have some impact on the definition of the gross tumor volume (GTV), decrease inter-observer variability and change the treatment planning. Organs or tumor motion always influenced the accuracy and quality of CT images in the thoracic malignancy, including esophageal cancer during free breathing cycle. To estimate the feasibility of the combined four-dimensional computed tomography with four-dimensional 18F-fluorodeoxyglucose positron emission tomography (4D PET/CT) in GTV delineation of esophageal cancer. We hypothesized that some standards can be obtained when defining GTV for esophageal cancer by using biological target volume from 4D-PET/CT images. Methods and Materials: This study was a prospective analysis, approved by local institutional review board (DMR98- IRB-171-1 and DMR98- IRB-171-2), of 4D-PET/CT in radiotherapy planning of esophageal cancer. Patients with histologically approved esophageal cancer who would undergo definitive radiotherapy, concurrent chemoradiotherapy or radical surgery were eligible for this study. Eighteen patients with esophageal squamous cell cancer were enrolled between December 2009 and January 2011. Each of them was administered intravenously with 370 MBq (10 mCi) of 18F-FDG and rested supine in a quiet and dimly room. Patients were positioned and simulated in a radiotherapy planning position using the Real-time Position Management system respiratory gating hardware (Varian Medical Systems Inc). Four-dimensional CT images with 2.50-mm slice thickness, and 4D PET images with two table positions, 7 minutes per position, were acquired. All phases of CT images and PET images were automatically fused for this gating study. In 4D images during respiratory cycle, an average phase of CT images was fused with average phase of FDG PETs for analysis of optimal threshold or standardized uptake values (SUV). PET-based GTV (GTVPET) was determined with 8 different threshold methods by autocontouring function at the AW workstation (Advantage SimTM 7.6.0, GE, Healthcare): SUV15%, SUV 2, SUV 2.5, SUV 20%, SUV 25%, SUV 30%, SUV 40% and SUV 50%. The information of tumor extent from the contrast CT scan, panendoscopy and endoscopic ultrasonography (EUS) were used when delineating the CT-based GTV (GTVCT). Excluding the adjacent metastatic lymph nodes, the volume of GTVCT was contoured as a reference tumor volume. To reduce inter-observer variations, at least 2 different radiation oncologists carried out the contouring of the tumors for each patient. GTVPET was compared with GTVCT by volume ratio (VR) and conformality index (CI). CI is the ratio of the volume of intersection of two volumes compared with the volume of union of the two volumes under comparison. VR is the ratio of two volumes, and the denominator is the volume of GTVCT. A suitable threshold level could be defined when GTVPET was observed to be the best fitness of the length, CI or VR from the GTVCT. Results: Automatic co-registrations of 4D CT-FDG PET were successful in 12 patients with 13 GTVCT. The fused images were not available in the other 6 patients. The median age was 48.5years (range, 38-76 years). All patients were men. Eleven lesions (85%) were T3 and T4 stage. EUS was performed for 9 patients (75%). The mean length of GTVCT was 5.73 ± 2.40cm (range, 1.75-10.01cm). The mean volume of GTVCT was 29.41 ± 19.14mL (range, 3.65-70.76 mL). The mean SUVmax was 13.26 ± 2. 78 (range, 9.4-16.9). The decision coefficient (R2) of tumor length difference at the threshold levels of SUV2.5, SUV20% and SUV25% were 0.79, 0.65 and 0.54, respectively. The mean VR ranged from 0.30 to 1.48 (0.86±0.24). The optimal VR, 0.98, close to 1, was at SUV 20% or SUV 2.5. All SUV thresholds compare with SUV 2.5, the p values of SUV15%, SUV40% and SUV50% are 0.007, 0.002, and 0.000, respectively. The mean CI ranged from 0.28 to 0.58. The best fitness for CI was at SUV 20% (0.58 ± 0.10) or SUV 2.5 (0.57 ± 0.13). All SUV thresholds compare with SUV20%, the p values of SUV40% and SUV50% are 0.014, and 0.000, respectively. Conclusions: This study demonstrated that 4D-PET/CT is applicable when contouring the GTV in radiation planning for esophageal cancer. The use of threshold levels of SUV 20% or SUV 2.5 achieves the optimal correlation with tumor length, VR and CI. To assess final treatment outcome, the benefits of RT planning using 4D-PET/CT need more clinical investigations.

博士
國立高雄應用科技大學
電機工程系博碩士班
103
Purpose: To assist the clinical decision making, we aim to develop a radiotherapy treatment planning clinical decision support system. We quantify the influence parameters for different radiotherapy techniques through Taguchi analytic method to investigate the optimal techniques by these parameters in different kind of breast cancer. We also develop an analytic normal tissue complication probability platform for planning evaluation. Materials and Methods: In total 20 early stage breast cancer patients (10-right and 10- left) were enrolled. Five different treatment techniques were used i.e. wedged-tangential fields (WT), intensity modulated radiation therapy (IMRT), hybrid IMRT (H-IMRT), volumetric modulated arc therapy (VMAT), and an innovative hybrid VMAT (H-VMAT) technique we proposed. Using the Taguchi analysis method to analysis the optimal influence parameters for corresponding technique with modified planning quality index (mPQI). With the optimal influence parameters, we compared different techniques in different breast cancer patients. In sequential right or left breast cancer, WT, IMRT, H-IMRT, VMAT and H-VMAT techniques comparison were made. In simultaneous integrated boost right or left breast cancers, IMRT, H-IMRT, VMAT and H-VMAT techniques comparison were done. In bilateral breast cancers, IMRT and VMAT have been compared. We use multiple quantitative indices, including conformity index (CI), homogeneity index(HI), modified planning quality index (mPQI), equivalent uniform dose (EUD), tumor control probability (TCP), normal tissue complication probability (NTCP), to evaluate these techniques for seeking the optimal techniques in different breast cancer treatment for clinical decision support.delivery efficiency. Results: By using Taguchi analysis method, there are different dominant control parameters in different techniques for breast cancers. The forward adjust process is needed to get better plan quality in WT. 6MV photon energy are suitable in H-IMRT technique in left sequencial mode (SQM) patients and VMAT technique in right SQM patients. For the comparison of 5 techniques in SQM breast cancer, all plans can achieve > 95% coverage in planning target volume (PTV), and the organ at risks (OARs) are better sparing in VMAT technique. For the comparison of 4 techniques in simultaneous integrated boost (SIB) breast cancer, the organ at risk is better sparing in VMAT technique. In bilateral breast cancer patients, VMAT technique has better dosimetric results in PTV or OARs.

碩士
國立臺灣大學
醫學工程學研究所
103
Lung cancer is one of the leading cause of cancer deaths worldwide, including Taiwan, across gender. In Taiwan, the male mortality rate of lung cancer is as high as 48.9%. Surgery is the best and effective method in the early stage of the lung cancer. However, only 15% of the diagnosed patients are suitable for early-stage surgery. Surgery only is no longer considered for those being diagnosed at the middle to the late stage. Treatment for patients with middle-stage and late-stage may involve chemotherapy, radiotherapy, or a concurrent chemoradiation therapy. Radiation therapy, which is one of the primary therapeutic approaches for non-small cell lung cancer, is a treatment that uses high-energy rays or particles that destroy lung cancer cells. Radiation-induced lung damage (RILD) is a severe complication of radiotherapy in lung cancer patients that presents as a progressive pulmonary injury affecting prognosis and quality of life in patients. In this study a longitudinal registration algorithm is proposed for evaluating the lung parenchyma change after radiotherapy and the correlation to the given radiation strength and distribution of dosage. The proposed registration algorithm overcomes the large parenchyma change which makes the registration much harder by using anatomical structures around the lung, including using spine for the reference set of rigid registration step; using three anatomical structures: bone structures surface, including sternal, rib and spine, airway wall and surface of lower lung to describe the longitudinal difference of breath holding degree. Reference points are sampled from these three anatomical feature structures for the further step of coherent point set registration. Registered by the proposed longitudinal registration algorithm developed by this study, the correlation of regional dose distribution with longitudinal parenchyma change has been evaluated and obvious parenchyma change in the region of radiation dosage above 22 Gy and in 3~7 month is observed.

Tese mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2022
A Radioterapia é uma das modalidades principais para tratamentos de foro oncológico que visa destruir a ação proliferativa das células cancerígenas e reduzir o volume tumoral. A sua ação terapêutica através do uso de radiação ionizante tem, subjacente, a máxima de irradiar o tumor com uma elevada dose, ao mesmo tempo que os órgãos de risco (OARs) adjacentes, são tanto quanto possível protegidos. Quando um tumor se localiza no pulmão ou abdómen superior, como no fígado ou pâncreas, o seu movimento devido à respiração pode alcançar até 4 cm, especialmente na direção crânio-caudal, aumentando as incertezas relativas à posição do tumor. No Centro Clínico Champalimaud (CCC), o planeamento convencional dos tratamentos de radioterapia faz uso de uma tomografia computadorizada (CT) que é adquirida aquando da respiração livre do doente e que, por isso, apresenta geralmente artefactos que podem ser uma fonte de erro durante o planeamento. Nos casos em que o movimento do tumor é considerável, é ainda adquirida uma tomografia computadorizada quadrimensional (4DCT) que consiste entre 8 e 10 CTs que representam fases do ciclo respiratório. Posteriormente, a 4DCT é utilizada para delinear o volume interno do alvo (ITV) que engloba toda a extensão do movimento do tumor. Apesar da estratégia do ITV garantir uma adequada cobertura do volume-alvo, os OARs ficam expostos a doses de radiação desnecessárias e a um maior risco de toxicidade. Este efeito é ainda mais preocupante em tratamentos hipofracionados, onde doses mais elevadas são administradas num número reduzido de frações. Nos últimos anos têm sido desenvolvidas estratégias que visam tornar os tratamentos de radioterapia mais eficazes. Uma delas é a reconstrução de uma CT que representa a posição média do doente ao longo do ciclo respiratório (Mid-P CT). Esta estratégia resulta em volumes de tratamento menores do que a estratégia do ITV, possibilitando o aumento da dose e maior controlo tumoral local. O primeiro passo para a reconstrução do Mid-P CT é o registo deformável de imagens (DIR) entre uma das fases da respiração (uma CT da 4DCT), definida como a fase de referência, e as restantes fases. Deste processo resultam campos vetoriais deformáveis (DVF) que contém informação do deslocamento dos tecidos. Os DVFs são subsequentemente utilizados para transformar cada uma das fases da respiração para a posição média. O método do Mid-P foi implementado com sucesso no Instituto do Cancro Holandês (NKI) em 2008. Apesar dos bons resultados clínicos, o número de centros de radioterapia que utiliza esta técnica é muito reduzido. Tal deve-se, por um lado, à inexistência de soluções comerciais com esta funcionalidade e, por outro, ao esforço necessário alocar para implementar e validar soluções desenvolvidas internamente. O presente projeto teve como principal objetivo implementar a estratégia do Mid-P no CCC (Portugal). Para tal, foi otimizado um módulo – RunMidP – desenvolvido para o software 3D Slicer, que calcula o Mid-P CT e estima a amplitude do movimento do tumor e OARs com base nos DVFs. Considerando que a precisão do módulo e a qualidade de imagem do Mid-P CT devem atender os requisitos para o planeamento em radioterapia, foram realizados testes para validar o módulo. Sempre que possível, a sua performance foi comparada com outras aplicações desenvolvidas para a implementação da técnica do Mid-P, nomeadamente com um protótipo desenvolvido pela empresa Mirada Medical Ltd. (Reino Unido) – Mirada – e com o software desenvolvido no NKI (Holanda) – Wimp. Os testes foram divididos em três estudos diferentes, cada um com um conjunto de dados diferente. No primeiro estudo (estudo A), foram utilizadas 4DCT de 2 fantomas digitais, cuja função respiratória e cardíaca foi modelada de forma simplificada, e de 18 doentes com tumores localizados no pulmão (N = 8), no fígado (N = 6) e no pâncreas (N = 4). Neste estudo, foram comparados dois algoritmos DIR disponíveis no software 3D Slicer, o Plastimatch e o Elastix, em termos da precisão do registo e da qualidade de imagem do Mid-P CT reconstruído. Foi ainda avaliado a capacidade dos softwares RunMidP e Mirada representarem corretamente a posição média do doente e as diferenças das amplitudes do movimento do tumor estimadas pelos dois softwares. No estudo B, foram realizados testes de verificação semelhantes aos supre mencionados, em imagens sintéticas provenientes de 16 doentes, desta vez com a vantagem de se conhecer o “verdadeiro” Mid-P CT e as “verdadeiras” amplitudes do movimento do tumor. Estes foram comparados com os resultados obtidos com os softwares RunMidP e Mirada. Ainda, as unidades de Hounsfield (HU) no Mid-P CT reconstruído por RunMidP e Mirada foram comparadas com as HU na fase de referência, de modo a verificar se os Mid P CTs produziriam diferenças dosimétricas relevantes. No último estudo (estudo C), a qualidade de imagem do Mid-P CT foi avaliada quantitativamente e qualitativamente. Durante a análise qualitativa, foi pedido a dois médicos especialistas que avaliassem a viabilidade dos Mid-P CTs, reconstruídos pelos três softwares (RunMidP, Mirada e Wimp), para o planeamento dos tratamentos. O tempo da reconstrução do Mid-P CT a partir da 4DCT foi de cerca de 1h. Ambos os algoritmos, Plastimach e Elastix, demonstraram ser adequados para DIR de imagens do pulmão e abdómen superior, com diferenças estatisticamente não significativas (p > 0.05) em termos da precisão do registo. Contudo, o Mid-P CT reconstruído com Elastix apresentou uma melhoria na qualidade de imagem, sendo assim o algoritmo DIR escolhido para ser implementado no RunMidP. Em termos de métricas aplicadas a contornos definidos manualmente, tais como a distância de Hausdorf (HD) e coeficiente de Dice (DSC), o erro do registo de imagem foi menor que 1 mm, dentro do contorno do tumor, e 2 mm no pulmão. Os Mid-P CTs reconstruídos com o RunMidP e Mirada apresentaram maiores diferenças, relativamente ao “verdadeiro” Mid-P CT, na região do diafragma e zonas de maior homogeneidade como, por exemplo, no ar presente no intestino. Contudo, para a maioria dos doentes do estudo B, o Mid-P CT reconstruído com o software Mirada apresentou maior índice de similaridade estrutural (SSIM) relativamente ao “verdadeiro” Mid-P CT. Estes resultados podem estar na origem do uso de diferentes algoritmos DIR, mas deveram-se principalmente a uma falha na aplicação das transformações deformáveis pelo módulo RunMiP que foi corrigida posteriormente. Ainda, as diferenças entre as amplitudes estimadas e previstas foram menores que 1 mm para 37 tumores (78,9%), que resultam em diferenças menores que 0.3mm quando convertidas em margens de planeamento. Para além disso, as diferenças nos valores de HU dos Mid-P CTs comparativamente à fase de referência foram, em média, de 1 HU no tumor e OARs. Foram também observadas melhorias na qualidade de imagem do Mid-P CT, nomeadamente um aumento da relação sinal-ruído (SNR) e diminuição dos artefactos. Estes resultados estão de acordo com a avaliação dos médicos que, em geral, consideraram que os Mid-P CTs reconstruídos pelos três softwares são adequados para o planeamento dos tratamentos. No entanto, os Mid-P CTs reconstruídos com dados 4DCT provenientes do CCC apresentaram classificações inferiores aos reconstruídos com dados 4DCT do NKI. Em suma, as modificações do algoritmo DIR Plastimach para Elastix e a correção do método para aplicar as transformações deformáveis, permitiram uma melhoria na qualidade de imagem do Mid P CT e melhor performance do algoritmo, respetivamente. O módulo RunMidP, neste projeto otimizado e validado, apresenta um forte potencial para a reconstrução e implementação da estratégia do Mid-P na clínica, com performance comparável a outras aplicações existentes (Mirada e Wimp). Atenção especial deve ser dada aos dados 4DCT de input que parecem afetar a qualidade de imagem final do Mid-P CT. No futuro, valerá a pena otimizar os parâmetros de aquisição e reconstrução da 4DCT de modo a melhorar a qualidade de imagem e, ainda, o módulo RunMidP pode potencialmente ser otimizado no que respeita ao tempo de reconstrução do Mid-P CT e à precisão do DIR.
Radiotherapy for tumours in the thorax and upper abdomen is challenging since they move notably with breathing. To cover the whole extent of tumour motion, relatively large margins are added to treatment volumes, posing a higher risk of toxicity for surrounding organs-at-risk (OARs). The Mid Position (Mid-P) method accounts for breathing motion by using deformable image registration (DIR) to transform all phases of a 4DCT scan to a time-weighted average 3DCT scan (Mid-P CT). The Mid-P strategy results in smaller treatment volumes, potentially boosting the delivery of hypofractionated treatments. To bring the Mid-P approach to the Champalimaud Clinical Centre (CCC), an in-house Mid position software module – RunMidP – was optimized. The module reconstructs the Mid-P CT and estimates breathing motion amplitudes of tumours and relevant OARs. In addition, this project presents a set of experiments to evaluate the performance of the Mid-P method and its feasibility for clinical implementation. The experiments were conducted throughout three different studies using 4DCT data from 18 phantoms and 23 patients. In Study A, the accuracy and image quality of two DIR algorithms (Plastimatch and Elastix) were assessed using quantitative metrics applied on either warped images or manually delineated contours. The reproduction of the patient’s mean position by the Mid-P CT and the estimation of motion amplitudes were compared to a soon-to-be Mid-P commercial software developed by Mirada Medical Ltd. In Study B,similar experiments were performed, this time using a more rigorous reference – “true” Mid-P CT scans and “true” motion estimations. In Study C, the image quality of Mid P CT scans was assessed quantitatively and qualitatively. Both Plastimatch and Elastix registration showed comparable registration accuracy, although Elastix showed superior image quality of reconstructed Mid-P CTs. Based on contour metrics, the registration error was less than 2 mm. In-house Mid-P CTs showed a slightly lower match to ground truth Mid-P CTs than the ones reconstructed by the Mirada prototype due to differences in DIR methods and small shifts to the original image geometry. Higher image differences were found in the diaphragm lung interface, where the patient's anatomy moves faster due to breathing, and in homogeneous regions such as the air regions in the bowel. On the other hand, differences (estimated-predicted) in motion amplitudes smaller than 1 mm were observed in 37 moving tumours (78.7%), showing a good performance of the Mid-P algorithm. Regarding the image quality, improvements in the signal-to-noise ratio and removal of image artefacts in Mid-P CTs are great advantages for using them as the planning CT. Clinicians also gave a good assessment of the suitability of Mid-P CT scans for treatment planning. No significant differences were found in the performance of the RunMidP compared to other Mid-Position packages, although worse scores were given to the CCC dataset than the dataset from another hospital. The in-house Mid-position algorithm shows promising results regarding the use of the software module in radiotherapy for lung and upper abdomen cancer. Further exploration must be given to improve the registration accuracy, image quality of the input data, and speed up the reconstruction of the Mid-P CT scan.

Ο σκοπός της διπλωματικής εργασίας ήταν η βελτιστοποίηση του πλάνου θεραπείας στο μαστό για τα 2 εφαπτόμενα συνεπίπεδα πεδία ενέργειας 6 MV. Η ανάγκη αυτή πρόκυψε από το γεγονός της εμφάνισης ελλείμματος στην κατανομή της δόσης καθώς όπως φαίνεται και στις παρακάτω εικόνες (στην αξονική και στην οβελιαία τομή) είχαμε ικανοποιητική κάλυψη του CTV στην περιφέρεια του μαστού αλλά στο κέντρο του CTV και σε μεγαλύτερα βάθη όχι. Για την πραγματοποίηση του παραπάνω σκοπού εφαρμόστηκαν 4 τεχνικές ακτινοβόλησης: 1. Δύο εφαπτόμενα συνεπίπεδα πεδία ενέργειας 6 MV, 2. Δύο εφαπτόμενα συνεπίπεδα πεδία ενέργειας 15 MV, 3. Δύο εφαπτόμενα συνεπίπεδα πεδία ενέργειας 6 MV + 1 Field In a Filed (FiF) πεδίο ενέργειας 15 MV και 4. . Δύο εφαπτόμενα συνεπίπεδα πεδία ενέργειας 6 MV + 2 Field In a Filed (FiF) πεδία ενέργειας 15 MV. Η παραπάνω μεθοδολογία εφαρμόστηκε σε πλήθος Ν=100 ασθενών, κατά 95% μεγέθους όγκου Τ1 (έως 2cm) και Τ2 (2-5 cm) και με αριθμό διηθημένων λεμφαδένων Ν<3. Ο υλικοτεχνικός εξοπλισμός που χρησιμοποιήθηκε για την υλοποίηση της εργασίας ήταν: 1. Αξονικός τομογράφος- Simulator Somatom Duo Siemens, 2. Σύστημα διαχείρισης (RVS) ακτινοθεραπευτικού τμήματος ARIA της VARIAN, 3. Σύστημα σχεδιασμού θεραπείας (TPS) Eclipse της VARIAN, 4. Σύστημα κλασσικού εξομοιωτή Aquity της VARIAN και 5. Γραμμικός Επιταχυντής ELEKTA SL 15. Για την στατιστική επεξεργασία των αποτελεσμάτων για πλήθος Ν=100 ασθενών χρησιμοποιήθηκε το πρόγραμμα IBM SPSS (Statistical Package for Social Sciences) έκδοση 20. Η στατιστική επεξεργασία έδειξε ότι μέσος όρος της μέσης δόσης για τις διάφορες τεχνικές ήταν 96.5%, 98.9%, 100.7%, 101.9% για τα 6MV, 15MV, 6MV + 1FIF 15MV και 6MV + 2FIF 15MV, αντίστοιχα. Τα 95% διαστήματα εμπιστοσύνης (Confidence Intervals) ήταν (96.2-96.8), (98.6-99.1), (100.4-100.9), (101.7-102.1) αντίστοιχα. Η ανάλυση έδειξε πως όλες οι ομάδες διέφεραν μεταξύ τους σε επίπεδο στατιστικής σημαντικότητας p < 0.001. Τα αποτελέσματα της εργασίας ήταν ότι η μέση δόση αυξάνεται από μέθοδο σε μέθοδο όπως έδειξε και η στατιστική ανάλυση, ο δείκτης ομοιογένειας μειώνεται αντίστοιχα από μέθοδο σε μέθοδο και αυτό αποτελεί δείγμα βελτίωσης της κατανομής της δόσης. Ακόμα ότι από ένα συγκεκριμένο όγκο του CTV και πάνω η καλύτερη μέθοδος αποδείχτηκε ότι είναι η 6MV + 2FIF 15MV, ενώ από ένα συγκεκριμένο όγκο του CTV και κάτω οι μέθοδοι έχουν περίπου την ίδια αποτελεσματικότητα. Τέλος όσον αφορά τα φυσιολογικά όργανα (organs at risk), τον αντίστοιχο πνεύμονα και την καρδιά, μετρήθηκε το V20 (ο όγκος του οργάνου που λαμβάνει από 2000 cGy και πάνω) και αποδείχτηκε ότι είναι ανεξάρτητο από την τεχνική ακτινοβόλησης.
The purpose of this thesis is to optimize the breast cancer treatment planning for the coplanar tangential fields of 6MV energy. The need for this arose as the dose distribution appears deficient both at the center and deeper in the CTV, as shown in the CT and sagittal images below, whereas the dose is satisfactory distributed at the perimeter of the breast. In order to accomplish that, there were applied 4 radiation techniques: 1. Two coplanar tangential fields of 6MV energy, 2. Two coplanar tangential fields of 15MV energy, 3. Two coplanar tangential fields of 6MV energy with Field in a Field (FiF) of 15MV energy and 4. Two coplanar tangential fields of 6MV energy with two Fields in a Field (FiF’s) of 15MV energy. The method above was applied on 100 patients. 95% of them had T1 tumor (T<2cm), T2 tumor (T=2-5cm) and a number of infiltrated lymph N<3. The equipment that has been used for the materialization of the procedure was: 1. A Computed Tomographer Somatom Duo Siemens, 2. An RVS system of VARIAN, 3. A TPS Eclipse system of VARIAN, 4. A Simulator Aquity of VARIAN and 5. A linear accelerator ELEKTA SL 15. Using the program IBM SPSS 20 (Statistical Package for Social Sciences), for a hundred patients, the statistical analysis showed that the average of the mean dose was 96.5% for the 6MV, 98.9% for the 15MV, 100.7% for the 6MV + 1 FIF of 15MV and 101.9% for the 6MV + 2 FIF of 15MV respectively (95% CI, p<0.001). There was an interaction between CTV size and mean dose, notably for large breasted patients (CTV>750cc). In this particular clinical scenario two 6MV tangential fields with 2 FIFs consistently outperformed the others. Minimum dose was also statistically different among all groups (p<0.05) except for the two FIF-less tangential fields with 6 and 15 MV. Interestingly, minimum dose (%) lacked a dependence on volume size. The result of this procedure was that the mean dose increases from method to method as it was obvious from the statistical analysis. The homogeneity index decreases respectively from method to method which indicates improvement of the dose distribution. It was also proved that, for certain large volumes of CTV the best method was the 6MV with two FIF’s of 15MV energy, whereas for smaller volumes of CTV the other three methods were of the same effectiveness. In conclusion, as far as the organs at risk concern, it has been found that the V20, of the heart and the right or left lung each time, is irrelevant of the technique that has been used each time.

Les néoplasies pulmonaires demeurent la première cause de décès par cancer au Québec représentant près de 6000 décès par année. Au cours des dernières années, la radiothérapie stéréotaxique d’ablation (SABR) s’est imposée comme un traitement alternatif à la résection anatomique pour les patients inopérables atteints d’un cancer pulmonaire non à petites cellules de stade précoce. Il s’agit d’une modalité de traitement qui permet d’administrer des doses élevées, typiquement 30-60 Gy en 1-8 fractions, dans le but de cibler précisément le volume de traitement tout en épargnant les tissus sains. Le Centre Hospitalier de l’Université de Montréal s’est muni en 2009 d’un appareil de SABR de fine pointe, le CyberKnife™ (CK), un accélérateur linéaire produisant un faisceau de photons de 6 MV dirigé par un bras robotisé, permettant d’administrer des traitements non-coplanaires avec une précision infra-millimétrique. Ce mémoire est dédié à la caractérisation de certains enjeux cliniques et physiques associés au traitement par CK. Il s’articule autour de deux articles scientifiques revus par les pairs. D’une part, une étude prospective clinique présentant les avantages de la SABR pulmonaire, une technique qui offre un excellent contrôle tumoral à long terme et aide au maintien de la qualité de vie et de la fonction pulmonaire. D’autre part, une étude de physique médicale illustrant les limites de l’acquisition d’images tomodensitométriques en auto-rétention respiratoire lors de la planification de traitement par CK.
Lung neoplasia remains the leading cause of cancer death accounting for nearly 6,000 deaths per year in Quebec. In recent years, stereotactic ablative radiotherapy (SABR) has emerged as an alternative treatment to anatomical resection for inoperable patients suffering from early stage non-small cell lung cancer. This technique can deliver highly focused doses such as 30-60 Gy in 1-8 fractions in order to target precisely the treatment volume while sparing healthy tissue. In 2009, the Centre Hospitalier de l’Université de Montréal acquired a robotic SABR apparatus, the CyberKnife™ (CK), a linear accelerator mounted on a moving arm producing non-coplanar photon beams of 6 MV with millimetric precision. This thesis presents two scientific peer reviewed articles adressing some clinical and physical challenges with CK. On one hand, a clinical prospective study reporting the advantages of lung SABR, a technic that offers excellent long-term tumor control and helps maintain the quality of life and lung function. On the other hand, a medical physics study exposing the limits of computed tomography scan acquisition in breath-holding for CK treatment planning.

碩士
高雄醫學大學
醫學放射技術學研究所
100
Purpose: The purpose of this study is to compare the radiation dose distribution inverse-planned intensity-modulated radiotherapy (ipIMRT) and helical TomoTherapy (HT) for breast cancer patients undergoing whole breast radiation with simultaneous integrated boost (SIB), which may be related to radiation-induced pneumonitis and cardiac mortality. To investigate whether some geometric/dosimetric indicators can be determined to estimate the normal tissue complication probability. Material and methods： Thirty-six patients with left breast cancer (clinical stage T1–2N0–1M0) were eligible for the trial. All patients generated their treatment planning from both HT and ipIMRT under the prescription of SIB technique. The whole breast and tumor bed were prescribed 50.4Gy and 60.2Gy, in 28 fractions, respectively. These parameters include conformity index（CI）、homogeneity index （HI）、different dose point and normal tissue complication probability. And three geometric parameters were measured for each patient: the thorax width/thickness ratio, breast volume and the angle of the nipple–sternum to nipple-chest wall. Results： The HI and CI were better in HT than in ipIMRT (p<0.001), and differenr dose points such as maximum dose、minimum dose and so on were more closer the prescribed dose. But there were more volume received lower dose（Ipsilateral lung V5Gy：HT about 71.7% vs ipIMR about 36.8%，p<0.001；Heart V5Gy：HT about 94.4% vs ipIMRT about 30.2%， p<0.001。）；there were more volume received more higher dose in ipIMRT（Ipsilaterla lung V20Gy：HT about 13.6% vs ipIMRT about 17.7%，p<0.001；Heart V30Gy：HT about 1.7% vs ipIMRT about 5.6%，p<0.001）. The NTCP was higher in HT than in ipIMRT. Three geometric parameters, the breast volume, angle and thorax width/thickness ratio, were the determining factors for evaluating the NTCP. Except, the breast volume, angle and thorax width/thickness ratio were the significant factor for evaluating the NTCP. When the thorax width/thickness ratio >1.6, the NTCP for heart will become double in ipIMRT；°the NTCP for ipsilateral lung of the angle>91°was 2.7times as great as the angle<91 in HT；the NTCP for ipsilateral lung of the breast volume<350c.c was 2.2 times greater than the breast volume>350c.c. Conclusion: Our results showed there were more volume received lower dose in HT. When the radiation oncologist judges which techniques is better to the patient, he should be think about the effect of the body characteristic and low dose carefully.