New methods for solving the inverse problem of radiotherapy planning

New methods for the automatic determination and optimization of irradiation parameters for percutaneous radiotherapy with high energy photons are developed. The methods are based on an irradiation technique with intensity-modulated radiation fields. The essential problem is therefore to determine the shape of the modulation profiles for the individual fields, based on the specified target dose distribution. This problem is called the inverse problem of radiotherapy planning. It is shown that this is the mirrored version of the problem of reconstructing an image from its projections, such as occurs in computed tomography (CT). Based on this fact, the methods for image reconstruction known from CT are consistently transferred to the optimization of radiotherapy. By appropriate modifications of the methods, special features characteristic for this new field of application are taken into account. This includes in particular the fact that no negative radiation intensities can be realized and that one is limited to a few fields for practical reasons. It is shown that in most cases seven or nine radiation fields are sufficient and that the use of more fields does not lead to clinically significant improvements. The main methods of image reconstruction, namely filtered back projection and iterative reconstruction technique, are used alternatively in CT. In the present application, on the other hand, these methods are used quasi “symbiotically”. The filtered back projection, referred to here as filtered projection is used to quickly determine a starting value for the modulation profiles. These initial profiles are further optimized by an iterative procedure corresponding to the iterative reconstruction technique. The introduction of penalty functions makes it possible for the first time to adequately consider medically indicated constraints. The iterative optimization procedure is based on an algorithm for three-dimensional dose calculation. Therefore, another focus of this work is the development of such an algorithm for intensity modulated radiation fields. Conventional dose calculation algorithms cannot adequately account for modulations. To verify the newly developed method, a first comparison of the dose calculated with it with measured data is carried out. The methods presented here allow the direct determination of the irradiation parameters without the trial and error procedure that is common today. In addition, dose distributions can be generated that are hardly feasible even with the most complex conventional irradiation techniques. These are especially those with extended concave areas. Some examples of this type are presented

Dose Conformation in Tumor Therapy with External Ionizing Radiation: Physical Possibilities and Limitations

The central problem in tumor irradiation is to deposit a high and spatially uniform dose in the tumor target volume while sparing the surrounding normal tissue as much as possible. The present work investigates how such an adaptation ("conformation") of the spatial dose distribution to arbitrarily shaped target volumes can be achieved, and where the physical limits lie. In particular, the specific possibilities of irradiation with different types of radiation are determined under these aspects, whereby a rough distinction is made between irradiation with charged and uncharged particles. Due to the different mechanisms of radiation-tissue interaction, a conformal dose distribution can be achieved with only one radiation field in the case of heavy charged particles; in the case of uncharged particles, several radiation fields from different directions are required. First, the possibilities and limits of dose conformation are evaluated theoretically. Analytical approximations for modeling dose distributions with uncharged and charged particles are developed. Within the framework of these approximations, the theory of the exponential Radon transform is used to determine the optimal parameters for obtaining a desired dose distribution. It is shown that for an infinite number of radiation fields in the plane, it is possible to adapt the high-dose region to arbitrarily shaped target volumes for both uncharged and charged particles. The dose in a small radiation-sensitive organ at risk in the immediate vicinity of the target volume can be reduced to small scatter contributions. In the case of charged particles, this is also possible for multiple organs at risk. Furthermore, the non-conformal "dose background" is always smaller for charged particles than for uncharged particles. In a more application-oriented chapter, an algorithm is developed for the optimization of dose distributions under practical boundary conditions, i.e. in three dimensions, with finitely many radiation fields and for finite resolutions of the beam shaping devices. To achieve optimal dose distributions, the use of fluence- and (in the case of charged particles) energy-modulated radiation fields is necessary. Especially in the case of uncharged particles, the technical prerequisites for this are not yet available in clinical practice. Therefore, newly developed approaches to fluence modulation for uncharged particles using a dynamically or quasi-dynamically driven "multileaf collimator" are presented. Furthermore, the first phantom experiment is described in which these generalized methods for achieving the best possible conformal dose distribution were realized with high-energy photons (15-MV bremsstrahlung spectrum). The high degree of practically achievable dose conformation is thus verified. Finally, a comparison of the optimized dose distributions achievable with photons and protons is performed for challenging clinical cases where conventional radiotherapy reaches its limits. The most important result is that irradiation with uncharged particles, and in particular with high-energy X-rays, can be optimized in such a way that, in all clinically relevant cases, tumor-conformal dose distributions can be achieved with relatively few (less than ten) radiation fields. The exposure of healthy tissue is naturally higher than for heavy charged particles. However, the tolerance dose values are not exceeded. Exceptions are the rare cases in which the target volume is surrounded on almost all sides by particularly radiation-sensitive risk organs. Only in these cases can a much better result be achieved with the technically more demanding heavy charged particle therapy

Use of radiobiological modeling in treatment plan evaluation and optimization of prostate cancer radiotherapy

There are many tools available that are used to evaluate a radiotherapy treatment plan, such as isodose distribution charts, dose volume histograms (DVH), maximum, minimum and mean doses of the dose distributions as well as DVH point dose constraints. All the already mentioned evaluation tools are dosimetric only without taking into account the radiobiological characteristics of tumors or OARs. It has been demonstrated that although competing treatment plans might have similar mean, maximum or minimum doses they may have significantly different clinical outcomes (Mavroidis et al. 2001). For performing a more complete treatment plan evaluation and comparison the complication-free tumor control probability (P+) and the biologically effective uniform dose (D ) have been proposed (Källman et al. 1992a, Mavroidis et al. 2000). The D concept denotes that any two dose distributions within a target or OAR are equivalent if they produce the same probability for tumor control or normal tissue complication, respectively (Mavroidis et al. 2001)..

Beam Positions Optimization to Achieve Improved CT Images with Limited Data

 In radiotherapy planning, margins are used to account for the uncertainties due to internal organ and patient motion as well as set-up error. Improvement in radiotherapy treatments may be achieved by reducing the set-up uncertainty and thus treatment margins allowing a higher dose to be delivered to the target volume. It is important to be able to verify the success of the treatment by determining the position of patient and the dose deposited in the patient at each fraction. One possibility for achieving this would be to collect limited information while the patient is on the treatment couch. The aim of this study is to develop a method for determining intelligent angles to use to reconstruct an image for dose verification.A method optimizing the angles based on an objective function is required. The methods developed here are based on image correlation and projection correlation that have been investigated previously. Two optimization methods, deterministic and stochastic (simulated annealing), were also assessed. The effectiveness and practicality of each of these combinations were compared

DEVELOPMENT OF A ROBUST TREATMENT DELIVERY FRAMEWORK FOR STEREOTACTIC BODY RADIOTHERAPY (SBRT) OF SYNCHRONOUS MULTIPLE LUNG LESIONS

Stereotactic body radiation therapy (SBRT) of lung tumors uses high doses of radiation to deliver high biological effective doses (BED) in very few fractions (1-5). With the use of highly conformal fields to cover the tumor without depositing large doses to non-cancerous structures, this technique has proven time and again to be successful at achieving high local control. However, frequently patients receiving SBRT are elderly with multiple medical comorbidities who may not tolerate long treatment times. Furthermore, many patients present with oligometastatic or multiple primary lung tumors. The success of SBRT on oligometastatic lung disease relies on physician experience with precise patient positioning and immobilization, not available in all clinics. Likewise, there is no standard framework to guide radiation oncology clinics experienced in SBRT with planning and treating multiple lung tumors synchronously. This dissertation explores the treatment planning methods available for the SBRT of multiple lung lesions and presents innovative solutions to the challenges in current practice. To begin, two treatment planning methods for multiple lesion SBRT are compared: treating each lesion individually with separate isocenters and treating all lesions at the same time with a single isocenter. Treating multiple lesions with multiple isocenters will increase the patient’s imaging and treatment time and the number of instances a radiation therapist must enter the treatment room, thus increasing the chances a patient will move from the setup position. Using an individual isocenter placed between the tumors and volumetric arc therapy (VMAT) to treat all tumors at the same time can reduce the treatment time, increasing patient comfort and decreasing the chance of movement from the treatment position. However, there is a chance of decreased target coverage and reduced BED due to small setup errors in the SBRT of synchronous lesions using a single-isocenter. The dissertation continues by quantifying this loss in target coverage using a novel simulation method. Simulations yielded average deviations of 27.4% (up to 72% loss) (p \u3c 0.001) from planned target coverage. The largest deviations from planned coverage and desired BED were seen for the smallest targets (\u3c 10 cc), some of which received \u3c 100 Gy BED, which is suboptimal for SBRT. Patient misalignment resulted in a substantial decrease in conformity and increase in the gradient index, violating major characteristics of SBRT. To minimize coverage loss due to small setup errors, a novel Restricted Single-Isocenter Stereotactic Body Radiotherapy (RESIST) treatment method was developed to provide efficient and effective treatments without substantially increasing treatment time. Lastly, RESIST was automated in the treatment planning system to allow for efficient and accurate treatment planning for two lung lesion SBRT. Automation includes beam geometry, algorithm selection, and an in-house trained dose volume histogram estimation model to improve plan quality. Automated planning significantly improves treatment planning time and decreases the chance of planning errors. This treatment delivery framework allows all patients who are to be treated with SBRT to multiple lung lesions to be treated efficiently and effectively. Further development of RESIST for \u3e 2 lesions and multi-site SBRT merits further investigation

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

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