Organ motion and inaccurate patient positioning may compromise radiation therapy outcome. With the aid of image guidance, it is possible to allow for a more accurate organ motion and motion control study, which could lead to the reduction of irradiated healthy tissues and possible dose escalation to the target volume to achieve better treatment results. The studies on the organ motion and image guidance were divided into the following four sections. The first, the interfractional setup uncertainties from day-to-day treatment and intrafractional internal organ motion within the daily treatment from five different anatomic sites were studied with Helical TomoTherapy unit. The pre-treatment mega voltage computed tomography (MVCT) provided the real-time tumor and organ shift coordinates, and can be used to improve the accuracy of patient positioning. The interfractional system errors and random errors were analyzed and the suggested margins for HN, brain, prostate, abdomen and lung were derived. The second, lung stereotactic body radiation therapy using the MIDCO BodyLoc whole body stereotactic localizer combined with TomoTherapy MVCT image guidance were investigated for the possible target and organ motion reduction. The comparison of 3D displacement with and without BodyLoc immobilization showed that, suppression of internal organ motion was improved by using BodyLoc in this study. The third, respiration related tumor motion was accurately studied with the four dimensional computed tomography (4DCT). Deformable registration between different breathing phases was performed to estimate the motion trajectory for lung tumor. Optimization is performed by minimizing the mean squared difference in intensity, and is implemented with a multi-resolution, gradient descent procedure. The fourth, lung tumor mobility and dosimetric benefits were compared with different PTV obtained from 3DCT and 4DCT. The results illustrated that the PTV3D not only included excess normal tissues but also might result in missed target tissue. The normal tissue complication probability (NTCP) from 4D plan was statistically significant smaller than 3D plan for both ipsilateral lung and heart.

Student Number : 9201769X - M Med research report - School of Clinical Medicine - Faculty of Health Sciences / A PROSPECTIVE RANDOMIZED TRIAL OF TWO FRACTIONATION REGIMENS OF RADIATION THERAPY IN THE MANAGEMENT OF AIDSASSOCIATED KAPOSI SARCOMA OBJECTIVE: To compare a standard fractionation scheme with a hypofractionated scheme in the treatment of AIDS-associated Kaposi sarcoma with the aim of showing noninferiority of the shorter schedule. PATIENTS AND METHODS: HIV positive patients with histologically proven Kaposi sarcoma presenting consecutively to Radiation Oncology at Johannesburg Hospital were randomized between January 2003 and May 2004 to receive a standard regimen of 24 Gy in 12 fractions (ARM A) or the study regimen of 20 Gy in 5 fractions (ARM B). The radiation technique used was individualized for each site in accordance with departmental practice. Follow-up assessment was done at monthly intervals. Treatment response and toxicity were recorded at each follow-up visit. RESULTS: A total of 60 patients were recruited, of which 41 were male and 19 were female. The median age was 36 years (range: 23 – 55 years). Thirteen patients died prior to receiving treatment. The remaining 47 patients were treated to 65 sites, of which 35 sites received 24 Gy in 12 fractions (ARM A) and 30 sites received 20 Gy in 5 fractions (ARM B). The main indications for treatment were pain (n=71), oedema (n=44), functional impairment (n=35), cosmesis (n=14) and bleeding (n=4). At the time of reporting 28 patients were alive and 32 patients have died. The overall survival of the whole group was 37% at 1 year. A complete response was recorded at 28 sites, a partial response at 19 sites and stable disease at 3 sites. The mean time to maximum objective response was 3 months (range: 1 – 14 months). The response rates were equal in the 2 treatment arms (p=0.73). Local control was equal in the 2 treatment arms with a median local recurrence free survival of 150 days for ARM A and 455 days for ARM B (p=0.11, log rank test). Acute skin toxicity occurred at 27 sites. Moist desquamation developed at 7 sites while necrosis developed at 2 sites. Acute skin toxicity was equal in the 2 treatment arms (p=0.77). Acute mucosal toxicity occurred at 2 sites. Late skin reactions developed at 21 sites, of which necrosis or ulceration occurred at 5 sites. Chronic skin reactions were equivalent in the 2 treatment arms (p=0.24). Post radiation oedema developed at 5 sites. CONCLUSION: In our experience, 20 Gy in 5 fractions gave similar results to 24 Gy in 12 fractions in terms of treatment response, local recurrence free survival and toxicity in this small group of patients.

A propriedade intelectual tem se tornado cada vez mais importante e é uma parte fundamental do desenvolvimento. No entanto, ainda é pouca literatura sobre a avaliação desses ativos intangíveis. Não se sabe ao certo sequer quais variáveis (idade, número de citações, atividade inventiva etc.), estabelecem o valor de uma patente, e essas variáveis podem diferir dependendo do setor. Também pouco se sabe sobre como se relacionam umas com as outras em termos de formação rotas tecnológicas, e quais fatores mais importantes para uma patente ser usada como inspiração para outra invenção. Neste trabalho são usadas análises de redes formadas pelas citações das patentes do segmento de equipamentos para radioterapia para descobrir o que os principais atores produziram nos últimos vinte anos no mercado de equipamentos para radioterapia. Foram levantados também os países de maior interesse de proteção dessas invenções, os principais atores no mercado. Tendências tecnológicas foram analisadas pelas formações de clusteres de reivindicações de tais documentos. Descobriu-se que a formação da rede e dos grupos de patentes têm como principal característica a semelhança das tecnologias envolvidas e, também, de fatores geográficos. Os principais playeres são grandes companhias de países desenvolvidos e praticamente não há proteção de invenções deste segmento em países emergentes ou subdesenvolvidos, com exceção da China. / Intellectual property has become increasingly important and is a key part of the development. However, it is still little literature on the valuation of these intangible assets. No one knows for sure even what variables (age, number of citations, inventive activity etc.), set the value of a patent, and these variables may differ depending on the sector. Also little is known about how they relate to each other in terms of technological routes formation, and which are the most important factors for a patent to be used as inspiration for other invention. This work analyzes the networks formed by the citations of the patents in the radiation therapy devices segment to find out what the main actors produced in the last twenty years in the radiotherapy equipment market. Countries of greatest interest to protect these inventions and the principal players were also pointed. Technological trends were identified by the formation of clusters of documents\' claims. It was found that the formation of the network and groups of patents have as main feature the likeness of the technologies involved, and also geographic factors. The main players are large companies from developed countries and there is virtually no protection for inventions in this segment in emerging or developing countries, excluding China.

Quality Assurance (QA) for medical linear accelerators (linac) is the primary concern in external beam radiation therapy. In this research, we have developed a MATLAB-based software named Quality Assurance for Linacs (QALMA), which is unique, due to cost-effectiveness, user friendly interface, and customizability. It includes five modules to perform different QA tests: Star Shot analysis, Picket Fence test, Winston-Lutz test, MLC log file analysis, and verification of light & radiation field coincidence. We also pay attention to quality assurance of 6DOF treatment couch that plays a very important role in radiation therapy. We developed an Arduino based 3D printed 6DOF robotic phantom to check the accuracy of the treatment couch. This robotic phantom was experimentally validated under clinical standards, and customizable upon requirements of the quality assurance Task. The current features of this robotic phantom open development opportunities beyond the specific couch application, such as organs motion simulation. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

The main function of the respiratory system is gas exchange. Since many disease or injury conditions can cause biomechanical or material property changes that can alter lung function, there is a great interest in measuring regional lung function and mechanics. In this thesis, we present a technique that uses multiple respiratory-gated CT images of the lung acquired at different levels of inflation with both breath-hold static scans and retrospectively reconstructed 4D dynamic scans, along with non-rigid 3D image registration, to make local estimates of lung tissue function and mechanics. We validate our technique using anatomical landmarks and functional Xe-CT estimated specific ventilation. The major contributions of this thesis include: 1) developing the registration derived regional expansion estimation approach in breath-hold static scans and dynamic 4DCT scans, 2) developing a method to quantify lobar sliding from image registration derived displacement field, 3) developing a method for measurement of radiation-induced pulmonary function change following a course of radiation therapy, 4) developing and validating different ventilation measures in 4DCT. The ability of our technique to estimate regional lung mechanics and function as a surrogate of the Xe-CT ventilation imaging for the entire lung from quickly and easily obtained respiratory-gated images, is a significant contribution to functional lung imaging because of the potential increase in resolution, and large reductions in imaging time, radiation, and contrast agent exposure. Our technique may be useful to detect and follow the progression of lung disease such as COPD, may be useful as a planning tool during RT planning, may be useful for tracking the progression of toxicity to nearby normal tissue during RT, and can be used to evaluate the effectiveness of a treatment post-therapy.

<p>Background: This is a retrospective study of patients treated with stereotactic body radiation therapy (SBRT) with the stereotactic body frame for centrally located lung tumours. The purpose was to investigate the doses to the different structures of the tracheobronchial tree and to relate these doses to the incidence of atelectasis. The goal was to estimate a tolerance dose for the bronchi. Materials: The patient material consisted of 71 patient treated at the Karolinska University Hospital for a total of 102 tumours between November 1993 and March 2004. The patient group consisted of 36 men and 35 women with a mean age at the treatment of 67 years (range 34-87). The group was a mixture of patients with primary lung cancer and pulmonary metastases. Methods: After rereading and reactivating the dose plans for the patients in the treatment planning system (TPS) the different tracheobronchial structures (trachea, right mainstem bronchus, right superior bronchus, right intermedius bronchus, right medius bronchus, right inferior bronchus, left mainstem bronchus, left superior bronchus, left intermedius bronchus, left inferior bronchus) were outlined. The dose distribution in each structure was calculated and a dose-volume histogram (DVH) was created. Patients were allocated to four groups, i.e. patients with right sided tumours (22), left sided tumours (14), mediastinal tumours (23) and bilateral tumours (10). After that the maximum and mean doses to all structures were analysed. An oncologist reviewed the medical records for the patients and especially looked for atelectasis. The doses were related to the incidence of atelectasis.</p><p>Results and Conclusions: For the patient group with right sided tumours it seems like the maximum doses to the bronchi are higher for the patients with atelectasis in comparison with patients without atelectasis. A better correlation between atelectasis and maximum doses rather than mean doses was observed for these patients. At this moment the results are too preliminary, so it is not possible to suggest a tolerance dose for the bronchi. What can be said is that the maximum doses to the bronchi for patients with right sided tumours without atelectasis are below 250 Gy3 expressed in biologically equivalent dose (BED) with α/β=3Gy, while at least one bronchi structure in the atelectasis patients received a maximum dose above 250 Gy3.</p>

<p>Background: Stereotactic body radiation therapy (SBRT) is a relatively new method which has been employed e.g. in the treatment of liver tumours. Little dosimetric data has been published for SBRT in the liver. The aim of this retrospective study was to quantify the dosimetric parameters that influence the toxicity of the healthy liver, and the effect on the tumour, for SBRT to liver tumours in patients treated at Karolinska University Hospital. A comparison was made to relating published studies.</p><p>Patients and Methods: The patient group to be studied were treated at Karolinska University Hospital for liver metastases with SBRT between July 1993 and October 2004. There were 64 patients treated with 71 treatment plans for 81 tumours. Differential dose volume histograms were collected for the clinical target volume (CTV), the planning target volume (PTV) and the liver excluding the CTV, from all dose plans. Since different fractionation schedules were used, the doses were normalised using the linear quadratic model, to be comparable. The doses to the uninvolved liver were evaluated with the mean liver dose, the Lyman-Kutcher-Burman (LKB) effective volume normal tissue complication probability (NTCP) model as well as the critical volume NTCP-model. A comparison was made to the studies of Dawson et al (2002) and Schefter et al (2005). The doses to the CTV were evaluated using the equivalent uniform dose tumour control probability (TCP) model, and related to target size and date of treatment.</p><p>Results: When the mean doses to the uninvolved liver (the liver volume without tumour tissue) were compared to Dawson and Ten Haken’s results (2005), 20 treatments out of 71 were predicted to give a risk of radiation induced liver disease (RILD) higher than 50%. The effective volume calculations predicted that 18 treatments gave a risk of RILD higher than 50%, when compared to the results of Dawson et al (2002). According to the critical volume model and the parameter values of Schefter et al (2005), our data predict that 10 of the treatments gave a risk of liver function failure, to an unspecified risk level. Treatments of large tumours resulted in higher doses to the liver. The doses to the CTV showed that the maximum prescribed dose decreased with increasing CTV.</p><p>Discussion and Conclusions: An evaluation of clinical data is necessary to make a full analysis of the treatments of this study. Such an analysis is planned for the future.</p>

The segmentation problem arises in the elaboration of a radiation therapy plan. After the cancer has been diagnosed and the radiation therapy sessions have been prescribed, the physician has to locate the tumor as well as the organs situated in the radiation field, called the organs at risk. The physician also has to determine the different dosage he wants to deliver in each of them and has to define a lower bound on the dosage for the tumor (which represents the minimum amount of radiation that is needed to have a sufficient control of the tumor) and an upper bound for each organ at risk (which represents the maximum amount of radiation that an organ can receive without damaging). Designing a radiation therapy plan that respects these different bounds of dosage is a complex optimization problem that is usually tackled in three steps. The segmentation problem is one of them. Mathematically, the segmentation problem amounts to decomposing a given nonnegative integer matrix A into a nonnegative integer linear combination of some binary matrices. These matrices have to respect the consecutive ones property. In clinical applications several constraints may arise that reduce the set of binary matrices which respect the consecutive ones property that we can use. We study some of them, as the interleaf distance constraint, the interleaf motion constraint, the tongue-and-groove constraint and the minimum separation constraint. We consider here different versions of the segmentation problem with different objective functions. Hence we deal with the beam-on time problem in order to minimize the total time during which the patient is irradiated. We study this problem under the interleaf distance and the interleaf motion constraints. We consider as well this last problem under the tongue-and-groove constraint in the binary case. We also take into account the cardinality and the lex-min problem. Finally, we present some results for the approximation problem. /Le problème de segmentation intervient lors de l'élaboration d'un plan de radiothérapie. Après que le médecin ait localisé la tumeur ainsi que les organes se situant à proximité de celle-ci, il doit aussi déterminer les différents dosages qui devront être délivrés. Il détermine alors une borne inférieure sur le dosage que doit recevoir la tumeur afin d'en avoir un contrôle satisfaisant, et des bornes supérieures sur les dosages des différents organes situés dans le champ. Afin de respecter au mieux ces bornes, le plan de radiothérapie doit être préparé de manière minutieuse. Nous nous intéressons à l'une des étapes à réaliser lors de la détermination de ce plan: l'étape de segmentation. Mathématiquement, cette étape consiste à décomposer une matrice entière et positive donnée en une combinaison positive entière linéaire de certaines matrices binaires. Ces matrices binaires doivent satisfaire la contrainte des uns consécutifs (cette contrainte impose que les uns de ces matrices soient regroupés en un seul bloc sur chaque ligne). Dans les applications cliniques, certaines contraintes supplémentaires peuvent restreindre l'ensemble des matrices binaires ayant les uns consécutifs (matrices 1C) que l'on peut utiliser. Nous en avons étudié certaines d'entre elles comme celle de la contrainte de chariots, la contrainte d'interdiciton de chevauchements, la contrainte tongue-and-groove et la contrainte de séparation minimum. Le premier problème auquel nous nous intéressons est de trouver une décomposition de la matrice donnée qui minimise la somme des coefficients des matrices binaires. Nous avons développé des algorithmes polynomiaux qui résolvent ce problème sous la contrainte de chariots et/ou la contrainte d'interdiction de chevauchements. De plus, nous avons pu déterminer que, si la matrice donnée est une matrice binaire, on peut trouver en temps polynomial une telle décomposition sous la contrainte tongue-and-groove. Afin de diminuer le temps de la séance de radiothérapie, il peut être désirable de minimiser le nombre de matrices 1C utilisées dans la décomposition (en ayant pris soin de préalablement minimiser la somme des coefficients ou non). Nous faisons une étude de ce problème dans différents cas particuliers (la matrice donnée n'est constituée que d'une colonne, ou d'une ligne, ou la plus grande entrée de celle-ci est bornée par une constante). Nous présentons de nouvelles bornes inférieures sur le nombre de matrices 1C ainsi que de nouvelles heuristiques. Finalement, nous terminons par étudier le cas où l'ensemble des matrices 1C ne nous permet pas de décomposer exactement la matrice donnée. Le but est alors de touver une matrice décomposable qui soit aussi proche que possible de la matrice donnée. Après avoir examiné certains cas polynomiaux nous prouvons que le cas général est difficile à approximer avec une erreur additive de O(mn) où m et n représentent les dimensions de la matrice donnée.

Background: This is a retrospective study of patients treated with stereotactic body radiation therapy (SBRT) with the stereotactic body frame for centrally located lung tumours. The purpose was to investigate the doses to the different structures of the tracheobronchial tree and to relate these doses to the incidence of atelectasis. The goal was to estimate a tolerance dose for the bronchi. Materials: The patient material consisted of 71 patient treated at the Karolinska University Hospital for a total of 102 tumours between November 1993 and March 2004. The patient group consisted of 36 men and 35 women with a mean age at the treatment of 67 years (range 34-87). The group was a mixture of patients with primary lung cancer and pulmonary metastases. Methods: After rereading and reactivating the dose plans for the patients in the treatment planning system (TPS) the different tracheobronchial structures (trachea, right mainstem bronchus, right superior bronchus, right intermedius bronchus, right medius bronchus, right inferior bronchus, left mainstem bronchus, left superior bronchus, left intermedius bronchus, left inferior bronchus) were outlined. The dose distribution in each structure was calculated and a dose-volume histogram (DVH) was created. Patients were allocated to four groups, i.e. patients with right sided tumours (22), left sided tumours (14), mediastinal tumours (23) and bilateral tumours (10). After that the maximum and mean doses to all structures were analysed. An oncologist reviewed the medical records for the patients and especially looked for atelectasis. The doses were related to the incidence of atelectasis. Results and Conclusions: For the patient group with right sided tumours it seems like the maximum doses to the bronchi are higher for the patients with atelectasis in comparison with patients without atelectasis. A better correlation between atelectasis and maximum doses rather than mean doses was observed for these patients. At this moment the results are too preliminary, so it is not possible to suggest a tolerance dose for the bronchi. What can be said is that the maximum doses to the bronchi for patients with right sided tumours without atelectasis are below 250 Gy3 expressed in biologically equivalent dose (BED) with α/β=3Gy, while at least one bronchi structure in the atelectasis patients received a maximum dose above 250 Gy3.

Background: Stereotactic body radiation therapy (SBRT) is a relatively new method which has been employed e.g. in the treatment of liver tumours. Little dosimetric data has been published for SBRT in the liver. The aim of this retrospective study was to quantify the dosimetric parameters that influence the toxicity of the healthy liver, and the effect on the tumour, for SBRT to liver tumours in patients treated at Karolinska University Hospital. A comparison was made to relating published studies. Patients and Methods: The patient group to be studied were treated at Karolinska University Hospital for liver metastases with SBRT between July 1993 and October 2004. There were 64 patients treated with 71 treatment plans for 81 tumours. Differential dose volume histograms were collected for the clinical target volume (CTV), the planning target volume (PTV) and the liver excluding the CTV, from all dose plans. Since different fractionation schedules were used, the doses were normalised using the linear quadratic model, to be comparable. The doses to the uninvolved liver were evaluated with the mean liver dose, the Lyman-Kutcher-Burman (LKB) effective volume normal tissue complication probability (NTCP) model as well as the critical volume NTCP-model. A comparison was made to the studies of Dawson et al (2002) and Schefter et al (2005). The doses to the CTV were evaluated using the equivalent uniform dose tumour control probability (TCP) model, and related to target size and date of treatment. Results: When the mean doses to the uninvolved liver (the liver volume without tumour tissue) were compared to Dawson and Ten Haken’s results (2005), 20 treatments out of 71 were predicted to give a risk of radiation induced liver disease (RILD) higher than 50%. The effective volume calculations predicted that 18 treatments gave a risk of RILD higher than 50%, when compared to the results of Dawson et al (2002). According to the critical volume model and the parameter values of Schefter et al (2005), our data predict that 10 of the treatments gave a risk of liver function failure, to an unspecified risk level. Treatments of large tumours resulted in higher doses to the liver. The doses to the CTV showed that the maximum prescribed dose decreased with increasing CTV. Discussion and Conclusions: An evaluation of clinical data is necessary to make a full analysis of the treatments of this study. Such an analysis is planned for the future.