京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22734号 / 医博第4652号 / 新制||医||1046(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 妹尾 浩, 教授 増永 慎一郎, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23081号 / 医博第4708号 / 新制||医||1049(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中本 裕士, 教授 小川 誠司, 教授 武田 俊一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19553号 / 医博第4060号 / 新制||医||1012(附属図書館) / 32589 / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 富樫 かおり, 教授 武田 俊一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20248号 / 医博第4207号 / 新制||医||1020(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 鈴木 実, 教授 別所 和久, 教授 大森 孝一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

In modern, advanced radiotherapy (e.g. intensity modulated photon radiotherapy, IMXT) the delivery time for each fraction becomes prolonged to 10-20 minutes compared with the conventional, commonly 2-5 minutes. The biological effect of this prolongation is not fully known. The large number of beam directions in IMXT commonly leads to a large integral dose in the patient. Electrons would reduce the integral dose but are not suitable for treating deep-seated tumour, due to their limited penetration in tissues. By combining electron and photon beams, the dose distributions may be improved compared with either used alone. One obstacle for using electron beams in clinical routine is that there is no available treatment planning systems that optimise electron beam treatments in a similar way as for IMXT. Protons have an even more pronounced dose fall-off, larger penetration depth and less penumbra widening than electrons and are therefore more suitable for advanced radiotherapy. However, proton facilities optimised for advanced radiotherapy are not commonly available. In some instances electron beams may be an acceptable surrogate. The first part of this study is an experimental in vitro study where the situation in a tumour during fractionated radiotherapy is simulated. The effect of the prolonged fraction time is compared with the predictions by radiobiological models. The second part is a treatment planning study to analyse the mixing of electron and photon beams for at complex target volume in comparison with IMXT. In the next step a research version of an electron beam optimiser was used for the improvement of treatment plans. The aim was to develop a method for translating crude energy and intensity matrices for optimised electrons into a deliverable treatment plan without destroying the dose distribution. In the final part, different methods of treating the spinal canal in medulloblastoma were explored in a treatment planning study that was evaluated with biological models for estimating risks for late radiation effects. The effect on cell survival of prolonging fraction time at conventional doses/fraction is significant in an in vitro system. This effect is underestimated by biological models. Prolonging the fraction time will spare tissues with a fast DNA repair. Thus, there is a risk for sparing tumours. The mixed electron and photon beam technique has the potential to treat deep-seated tumours. Compared with IMXT the number of beams can be reduced and as a consequence, the time for each fraction could be kept shorter. The integral dose in the patient will also be lower. The mixed beam technique could potentially be further improved if automatic optimisation for electrons was available. The results suggest that optimisation and segmentation can be automated, and a deliverable treatment plan can be obtained with simple procedures without destroying the quality of the dose distribution. The integral dose in patients may lead to late radiation side effects. In childhood cancers the risk for development of radiation induced cancers is a reality and the integral dose outside the target volume should be minimised. Based on models for cancer induction, protons show the lowest risk while electrons have some benefit compared with different photon techniques. All methods are able to similarly well treat the target volume.

In this thesis, optimization approaches for intensity-modulated radiation therapy are developed and evaluated with focus on numerical efficiency and treatment delivery aspects. The first two papers deal with strategies for solving fluence map optimization problems efficiently while avoiding solutions with jagged fluence profiles. The last two papers concern optimization of step-and-shoot parameters with emphasis on generating treatment plans that can be delivered efficiently and accurately. In the first paper, the problem dimension of a fluence map optimization problem is reduced through a spectral decomposition of the Hessian of the objective function. The weights of the eigenvectors corresponding to the p largest eigenvalues are introduced as optimization variables, and the impact on the solution of varying p is studied. Including only a few eigenvector weights results in faster initial decrease of the objective value, but with an inferior solution, compared to optimization of the bixel weights. An approach combining eigenvector weights and bixel weights produces improved solutions, but at the expense of the pre-computational time for the spectral decomposition. So-called iterative regularization is performed on fluence map optimization problems in the second paper. The idea is to find regular solutions by utilizing an optimization method that is able to find near-optimal solutions with non-jagged fluence profiles in few iterations. The suitability of a quasi-Newton sequential quadratic programming method is demonstrated by comparing the treatment quality of deliverable step-and-shoot plans, generated through leaf sequencing with a fixed number of segments, for different number of bixel-weight iterations. A conclusion is that over-optimization of the fluence map optimization problem prior to leaf sequencing should be avoided. An approach for dynamically generating multileaf collimator segments using a column generation approach combined with optimization of segment shapes and weights is presented in the third paper. Numerical results demonstrate that the adjustment of leaf positions improves the plan quality and that satisfactory treatment plans are found with few segments. The method provides a tool for exploring the trade-off between plan quality and treatment complexity by generating a sequence of deliverable plans of increasing quality. The final paper is devoted to understanding the ability of the column generation approach in the third paper to find near-optimal solutions with very few columns compared to the problem dimension. The impact of different restrictions on the generated columns is studied, both in terms of numerical behaviour and convergence properties. A bound on the two-norm of the columns results in the conjugate-gradient method. Numerical results indicate that the appealing properties of the conjugate-gradient method on ill-conditioned problems are inherited in the column generation approach of the third paper. / QC 20100709

This dissertation investigates optimization approaches applied to radiation therapy in cancer treatment. Since cancerous cells are surrounded by critical organs and normal tissues, there is conflicting objectives in the treatment design of providing sufficient radiation dose to tumor region, while avoiding normal healthy cells. In general, the goal of radiation therapy is to conform the spatial distribution of the prescribed dose to the tumor volume while minimizing the dose to the surrounding normal structures. A recent advanced technology, using multi-leaf collimator integrated into linear accelerator, provides much better opportunities to achieve this goal: the radiotherapy based on non-uniform radiation beams intensities is called Intensity-Modulated Radiation Therapy. My dissertation research offers a quadratic mixed integer programming approach to determine optimal beam orientations and beamlets intensity simultaneously. The problems generated from real patient cases are large-scale dense instances due to the physics of dose contributions from beamlets to volume elements. The research highlights computational techniques to improve solution times for these intractable instances. Furthermore, results from this research will provide plans that are clinically acceptable and superior in plan quality, thus directly improve the curity rate and lower the normal tissue complication for cancer patients.

This thesis investigates the exact minimisation of treatment delivery time for Intensity Modulated Radiation Therapy (IMRT) for the treatment of cancer using Multileaf Collimators (MLC). Although patients are required to remain stationary during the delivery of IMRT, inevitably some patient movement will occur, particularly if treatment times are longer than necessary. Therefore minimising the treatment delivery time of IMRT may result in less patient movement, less inaccuracy in the dosage received and a potentially improved outcome for the patient. When IMRT is delivered using multileaf collimators in 'step and shoot' mode, it consists of a sequence of multileaf collimator configurations, or shape matrices; for each, time is needed to set up the configuration, and in addition the patient is exposed to radiation for a specified time, or beam-on time. The 'step and shoot leaf sequencing' problems for minimising treatment time considered in this thesis are the constant set-up time Total Treatment Time (TTT) problem and the Beam-on Time Constrained Minimum Cardinality (BTCMC) problem. The TTT problem minimises a weighted sum of total beam-on time and total number of shape matrices used, whereas the BTCMC problem lexicographically minimises the total beam-on time then the number of shape matrices used in a solution. The vast majority of approaches to these strongly NP-hard problems are heuristics; of the few exact approaches, the formulations either have excessive computation times or their solution methods do not easily incorporate multileaf collimator mechanical constraints (which are present in most currently used MLC systems). In this thesis, new exact mixed integer and integer programming formulations for solving the TTT and BTCMC problems are developed. The models and solution methods considered can be applied to the unconstrained and constrained versions of the problems, where 'constrained' refers to the modelling of additional MLC mechanical constraints. Within the context of integer programming formulations, new and existing methods for improving the computational efficiency of the models presented are investigated. Numerical results for all variations considered are provided. This thesis demonstrates that significant computational improvement can be achieved for the exact mixed integer and integer programming models investigated, via solution approaches based on an idea of systematically 'stepping-up' through the number of shape matrices used in a formulation, via additional constraints (particularly symmetry breaking constraints) and via the application of improved bounds on variables. This thesis also makes a contribution to the wider field of integer programming through the examination of an interesting substructure of an exact integer programming model. In summary, this thesis presents a thorough analysis of possible integer programming models for the strongly NP-hard 'step and shoot' leaf sequencing problems and investigates and applies methods for improving the computational efficiency of such formulations. In this way, this thesis contributes to the field of leaf sequencing for the application of Intensity Modulated Radiation Therapy using Multileaf Collimators.

Thesis--University of Oklahoma. / Bibliography: leaves 115-119.

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