O tratamento do câncer de próstata com o implante permanente das sementes de iodo-125 cresceu expressivamente nos Estados Unidos da América nos últimos anos. A técnica também vem sendo utilizada por hospitais e clínicas particulares no Brasil. As sementes utilizadas são importadas a custos elevados, o que as tornam proibitivas para uso em hospitais públicos, pois um implante requer, pelos menos, 80 sementes. Para minimizar custos financeiros e possibilitar a distribuição para entidades de saúde pública, iniciou-se o desenvolvimento da técnica de produção das sementes no País. A soldagem a laser é uma das técnicas de selagem da semente de iodo-125, que é feita nas duas extremidades do tubo de titânio, de modo a permitir a classificação da semente como fonte selada, atendendo aos rigorosos testes estabelecidos nas normas ISO 2919 e ISO 9978. O objetivo deste trabalho foi estudar e desenvolver um sistema alternativo de soldagem a laser Nd:YAG para sementes de iodo-125, com o propósito de fornecer dados de projeto e parâmetros operacionais para implantação de uma produção rotineira automatizada no IPEN-CNEN/SP. O desenvolvimento do trabalho apresentou as seguintes fases: corte e limpeza do material (tubo de titânio), projeto, fabricação e montagem de um sistema completo automatizado para a soldagem dos tubos de titânio, determinação dos parâmetros de soldagem (feixe de laser, gás de assistência e focalização), ensaios dos corpos de prova soldados e avaliação da repetitibilidade e eficiência do sistema. O sistema de soldagem a laser desenvolvido mostrou-se eficaz em virtude do eficiente processo de automação utilizado, capaz de produzir sementes de iodo-125 com soldas de qualidade que atendem aos critérios dos severos ensaios determinados nas normas ISO 2919 e ISO 9978. / The treatment for prostate cancer by permanent implant of iodine-125 seeds has increased significantly in the United States of America in recent years. This technique has also been used by hospitals and private clinics in Brazil. The seeds used are imported at a high cost, which makes them prohibitive for use in public hospitals, since an implant requires, at least, 80 seeds. In order to reduce the financial costs and enable the distribution to public health institutions, the technique for the seeds production in the country has been developed. The laser welding is one of the possible procedures to seal the iodine-125 seeds and it will be performed in both ends of the titanium tube: this will allow the seed classification as a sealed source, meeting the rigorous assays established by the ISO 2919 and the ISO 9978 standards. The objective of this research was to study and develop an alternative Nd:YAG laser welding system for iodine-125 seeds, with the purpose of providing project data and operational parameters for the implementation of an automated routine production at IPEN-CNEN/SP. The development of this work presented the following phases: the material (titanium tube) cutting and cleaning, the project, manufacture and assembly of a complete automated system to weld the titanium tubes. The determination of the welding parameters (laser beam, shield gas and focus), the assays of the welded specimens and the evaluation of repeatability and system efficiency have, also, been carried out. The laser welding system developed showed to be efficient for the automation process used and capable of producing seeds of iodine-125 with high quality weldings, meeting the criteria for the severe assays determined by the ISO 2919 and the ISO 9978.

Functional proton-beam stereotactic radiosurgery requires sub-millimeter alignment accuracy. A patient tracking system called Sequential Alignment and Position Verification System (SAVPS) is under development at Loma Linda University Medical Center. An optical positioning system (OPS), manufactured by Vicon Peak, has been chosen to verify the correct alignment of the target with the proton beam axis. The main objective of this thesis is to optimize an existing version of SAVPS by conducting error analysis. An image processing algorithm was developed and applied to estimate the error introduced by the Patient Positioning System (PPS) in order to derive the true error of the SAVPS.

This dissertation describes the application of two principled variance reduction strategies to increase the efficiency for two applications within medical physics. The first, called correlated Monte Carlo (CMC) applies to patient-specific, permanent-seed brachytherapy (PSB) dose calculations. The second, called adjoint-biased forward Monte Carlo (ABFMC), is used to compute cone-beam computed tomography (CBCT) scatter projections. CMC was applied for two PSB cases: a clinical post-implant prostate, and a breast with a simulated lumpectomy cavity. CMC computes the dose difference between the highly correlated dose computing homogeneous and heterogeneous geometries. The particle transport in the heterogeneous geometry assumed a purely homogeneous environment, and altered particle weights accounted for bias. Average gains of 37 to 60 are reported from using CMC, relative to un-correlated Monte Carlo (UMC) calculations, for the prostate and breast CTV’s, respectively. To further increase the efficiency up to 1500 fold above UMC, an approximation called interpolated correlated Monte Carlo (ICMC) was applied. ICMC computes using CMC on a low-resolution (LR) spatial grid followed by interpolation to a high-resolution (HR) voxel grid followed. The interpolated, HR is then summed with a HR, pre-computed, homogeneous dose map. ICMC computes an approximate, but accurate, HR heterogeneous dose distribution from LR MC calculations achieving an average 2% standard deviation within the prostate and breast CTV’s in 1.1 sec and 0.39 sec, respectively. Accuracy for 80% of the voxels using ICMC is within 3% for anatomically realistic geometries. Second, for CBCT scatter projections, ABFMC was implemented via weight windowing using a solution to the adjoint Boltzmann transport equation computed either via the discrete ordinates method (DOM), or a MC implemented forward-adjoint importance generator (FAIG). ABFMC, implemented via DOM or FAIG, was tested for a single elliptical water cylinder using a primary point source (PPS) and a phase-space source (PSS). The best gains were found by using the PSS yielding average efficiency gains of 250 relative to non-weight windowed MC utilizing the PPS. Furthermore, computing 360 projections on a 40 by 30 pixel grid requires only 48 min on a single CPU core allowing clinical use via parallel processing techniques.

Background and purpose: Historically HDR brachytherapy treatment planning systems ignore the transit dose in the computation of patient dose. However, the total radiation dose delivered during each treatment cycle is equal to the sum of the static dose and the transit dose and every HDR application therefore results in two radiation doses. Consequently, the absorbed dose to the target volume is more than the prescribed dose as computed during treatment planning. The aim of this study was to determine the magnitude of the transit dose component of two 192Ir HDR brachytherapy units and assess its dosimetric significance. Materials and Methods: Ionization chamber dosimetry systems (well-type and Farmertype ionization chambers) were used to measure the charge generated during the transit of the 192Ir source from a GammaMed and a Nucletron MicroSelectron HDR afterloader using single catheters of lengths 120 cm. Different source configurations were used for the measurements of integrated charge. Two analysis techniques were used for transit time determination: the multiple exposure technique and the graphical solution of zero exposure. The transit time was measured for the total transit of the radioactive source into (entry) and out of (exit) the catheters. Results: A maximum source transit time of 1.7 s was measured. The transit dose depends on the source activity, source configuration, number of treatment fractions, prescription dose and the type of remote afterloader used. It does not depend on the measurement technique, measurement distance or the analysis technique used for transit time determination. Conclusion: A finite transit time increases the radiation dose beyond that due to the programmed source dwell time alone. The significance of the transit dose would increase with a decrease in source dwell time or a higher activity source.

O objetivo deste trabalho é desenvolver um sistema de automação para a produção das sementes de iodo-125 por soldagem a laser (Nd:YAG). As sementes de iodo- 125 são utilizadas com sucesso no tratamento de câncer por braquiterapia, via baixa taxa de dose. Esta pequena semente é constituída por uma cápsula de titânio soldada, com 0,8mm de diâmetro e 4,5mm de comprimento, contendo iodo-125 adsorvido em fio de prata, no interior da mesma. As sementes de iodo-125 são implantadas na próstata humana para irradiar o tumor e tratar o câncer. Hoje, o Centro de Tecnologia das Radiações - CTR, do IPEN-CNEN/SP importa e distribui 36.000 sementes de iodo-125 por ano, para as clínicas e hospitais no País. No entanto, o potencial do mercado brasileiro é de 8.000 sementes de iodo-125 por mês. Assim, a produção local destas fontes radioativas de iodo- 125 tornou-se uma prioridade para o Instituto, visando reduzir o preço e aumentar o fornecimento à população. Por outro lado, a automação industrial desempenha papel importante na fabricação das sementes de iodo-125, com aumento da produtividade e padrão elevado de qualidade, além de facilitar a implementação e o funcionamento de processos com Boas Práticas de Fabricação (BPF). A tecnologia consiste em associar peças mecânicas e componentes eletro-eletrônicos, para controle de máquinas e processos. A tecnologia de automação para produção das sementes de iodo-125 desenvolvida neste trabalho emprega Controlador Lógico Programável (CLP), motores de passos, drivers, máquina de soldagem a laser (Nd:YAG), sensores fotoelétricos e interfaces de comunicação. / The aim of this work is to develop an automation system for iodine-125 radioactive seed production by (Nd:YAG) laser welding, which has been used successfully in Low Dose Rate (LDR) brachytherapy treatment. This small seed consists of a welded titanium capsule, with 0.8mm in diameter and 4.5mm in length, containing iodine-125 adsorbed onto a silver rod. The iodine-125 seeds are implanted into the human prostate to irradiate the tumor for cancer treatment. Nowadays, the Radiation Technology Center, at IPEN-CNEN/SP imports and distributes 36,000 iodine-125 seeds per year, for the clinics and hospitals in the country. However, the Brazilian market potential is now over 8,000 iodine-125 seeds per month. The local production of these iodine-125 radioactive sources becomes a priority for the Institute, in order to reduce the price and the problems of prostate cancer management. It will permit to spread their use to a largest number of patients in Brazil. On the other hand, the industrial automation plays an important role for iodine-125 seeds in order to increase the productivity, with high quality and assurance, avoiding human factors, implementing and operating with Good Manufacturing Practices (GMP). The technology consists of appliance electronic and electro-mechanical parts and components to control machines and processes. The automation system technology for iodine-125 seed production developed in this work was mainly assembled employing Programmable Logic Controller (PLC), stepper motors, drivers, (Nd:YAG) laser welding machine, photoelectric sensors and supervisory.

Intracavitary high dose rate (HDR) brachytherapy is a form of radiation therapy generally in which a post-surgical tissue margin is treated. The dose gradient of HDR brachytherapy is very steep, and thus small displacements of the applicator, even as small as 1 mm, could potentially cause significant variations of dose which could result in undesired side effects such as overdose of a critical organ. In this retrospective dosimetric study, the variation of dose due to various small range motions of gynecological applicators is investigated. The results show that the implementation of additional immobilization and localization devices along with other safety measures needs to be further investigated. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015 / FAU Electronic Theses and Dissertations Collection

Orientador: Marco Antônio Rodrigues Fernandes / Resumo: O uso de fontes de radiações ionizantes tem sido cada vez mais presente nas diversas atividades técnico-científicas. Os cuidados e os benefícios da prática já são bastante conhecidos e difundidos na área da medicina de humanos, tanto no campo do diagnóstico quanto da terapia. Na área da medicina veterinária, a radioterapia vem ganhando espaço, no entanto, o uso de feixes de radiações ionizantes exige o conhecimento de legislações específicas sobre proteção radiológica e a atuação de profissionais altamente especializados. O uso seguro das práticas de radioterapia requer o dimensionamento de blindagens para a correta proteção dos profissionais, dos pacientes e do meio ambiente. Neste trabalho foram realizados cálculos de blindagem para dimensionamento das espessuras das barreiras de proteção à radiação para uma sala de radioterapia adequada para o uso de um equipamento de teleterapia de ortovoltagem, destinado para procedimentos de radioterapia em medicina veterinária. Foram também realizados estudos para o dimensionamento das mesmas barreiras e condições de trabalho para o uso em braquiterapia de alta e de baixa taxa de dose (BATD e BBTD), para diferentes fontes radioativas. Foram ainda desenvolvidos os cálculos para dimensionamento das paredes de um espaço localizado no interior do canil situado no prédio da Faculdade de Medicina Veterinária e Zootecnia da Unesp de Botucatu (FMVZ), visando sua adequação para a realização de procedimentos de braquiterapia de baixa de dose. Os... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The use of ionizing radiation surces has increased in various technical-scientific activities. The care and benefits of the practice are already well known and widespread in human medicine, both in the field of diagnosis and therapy. In the area of veterinary medicine, radiotherapy has been gaining space, however, the use of ionizing radiation beams requires the knowledge of specific legislation on radiolprotection and specialized professionals. The safe use of radiotherapy practices requires the design of shielding for the correct protection of professionals, patients and the environment. The present study calculated the dimension and thickness of the radiation protection barriers to a radiotherapy room suitable for the use of orthovoltage teletherapy equipment, destined for radiotherapy procedures in veterinary medicine. Studies were also carried out for the design of the same barriers and working conditions for use in high and low dose rate brachytherapy (HDR and LDR) for different radioactive sources. The calculations for dimensioning the walls of a dog kennel located in the school of Veterinary Medicine and Animal Science, Unesp Botucatu (FMVZ), were also developed, aiming at their adequacy for the accomplishment of dose rate brachytherapy procedures. The results showed that the thicknesses calculated for the walls of the orthovoltage radiotherapy room are sufficient for the shielding of the radiations from the sources of high and low dose rate brachytherapy. / Mestre

Introduction Treating localized prostate cancer with combination radiotherapy consisting ofexternal beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) has beenproven to result in better disease outcome than EBRT only. There is, however, a decreasingtrend in utilization of combination therapy, partially due to concerns for elevated toxicityrisks. Aim To determine which parameters correlate to acute and late (≤ 6 months) urinary toxicity(AUT and LUT) and acute and late rectal toxicity (ART and LRT), and thereafter createpredictive models for rectal toxicity. Methods Data on toxicity rates and 32 patient, tumor and treatment parameters were collectedfrom 359 patients treated between 2008 and 2018 with EBRT (42 Gy in 14 fractions) andHDR-BT (14.5 Gy in 1 fraction) for localized prostate cancer at Örebro University Hospital.Bivariate analyses were conducted on all parameters and the outcome variables AUT, LUT,ART and LRT grade ≥ 1, graded according to the RTOG-criteria. Parameters correlating toART and LRT in this and previous studies were included in multivariate logistic regressionanalyses for creation of predictive models. Results Most toxicities, 86%, were of grade 0 or 1, only 9% of patients had grade 2 – 3toxicity. Only 2 – 4 parameters correlated to the respective toxicities in bivariate analyses.Logistic regressions generated no significant predictors of ART or LRT. Therefore, nopredictive models were obtained. Conclusion None of the included parameters have enough discriminative abilities regardingrectal toxicity. Predictive models can most probably be obtained by including otherparameters and more patients.

The thesis aims to improve treatment dose accuracy in brachytherapy using a high dose rate (HDR) Ir-192 stepping source and in external beam therapy using intensity modulated radiation therapy (IMRT). For HDR brachytherapy, this has been achieved by investigating dose errors in the near field and the transit dose of the HDR brachytherapy stepping source. For IMRT, this study investigates the volume effect of detectors in the dosimetry of small fields, and the clinical implementation and dosimetric verification of a 6MV photon beam for IMRT. For the study of dose errors in the near field of an HDR brachytherapy stepping source, the dose rate at point P at 0.25 cm in water from the transverse bisector of a straight catheter was calculated with Monte Carlo code MCNP 4.A. The Monte Carlo (MC) results were used to compare with the results calculated with the Nucletron Brachytherapy Planning System (BPS) formalism. Using the MC calculated radial dose function and anisotropy function with the BPS formalism, 1% dose calculation accuracy can be achieved even in the near field with negligible extra demand on computation time. A video method was used to analyse the entrance, exit and the inter-dwell transit speed of the HDR stepping source for different path lengths and step sizes ranging from 2.5 mm to 995 mm. The transit speeds were found to be ranging from 54 to 467 mm/s. The results also show that the manufacturer has attempted to compensate for the effects of inter-dwell transit dose by reducing the actual dwell time of the source. A well-type chamber was used to determine the transit doses. Most of the measured dose differences between stationary and stationary plus inter-dwell source movement were within 2%. The small-field dosimetry study investigates the effect of detector size in the dosimetry of small fields and steep dose gradients with a particular emphasis on IMRT measurements. Due to the finite size of the detector, local discrepancies of more than 10 % are found between calculated cross profiles of intensity modulated beams and intensity modulated profiles measured with film. A method to correct for the spatial response of finite sized detectors and to obtain the

Po radikalaus gydymo 20–50 proc. pacientų, kuriems nustatytas galvos–kaklo srities vėžys lokoregioninis atkrytis nustatomas per pirmus dvejus metus. Literatūroje paskelbtų tyrimų rezultatai taikant pakartotinę nuotolinę spindulinę terapiją dėl galvos-kaklo vėžio atkryčio prasti: 2-jų metų bendras išgyvenimas siekė 15,2–40 proc., vėlyvųjų 3-4 laipsnio komplikacijų dažnis buvo 1,4–47 proc., 5 laipsnio - 7,6 proc. Retrospektyvinių ir II fazės tyrimų rezultatai naudojant didelės dozės galios brachiterapiją galvos-kaklo srities vėžio atkryčiui gydyti: 2-jų metų bendras išgyvenimas siekė 19–63 proc., vėlyvųjų 3-4 laipsnio komplikacijų dažnis buvo 4–22,2 proc. Tyrimų metu skirtos 3–4 Gy frakcijos iki 30–40 Gy suminės dozės. Iki šiol neatlikti tyrimai lyginantys nuotolinės spindulinės terapijos ir didelės dozės galios brachiterapijos gydymo veiksmingumą ir saugumą. Šioje disertacijoje palyginti skirtingi spindulinio gydymo metodai gydant galvos-kaklo srities vėžio atkrytį: kontrolinei grupei taikytas nuotolinis konforminis spindulinis gydymas (25 frakcijos po 2 Gy, suminė dozė 50 Gy), tiriamajai grupei - hipofrakcionuota didelės dozės galios brachiterapija skiriant naują frakcionavimo režimą – po 2,5 Gy per frakciją po dvi frakcijas per dieną, iki 30 Gy suminės dozės. Toks frakcionavimo režimas pasirinktas siekiant sumažinti spindulinių reakcijų dažnį ir sunkumo laipsnį, o suminė dozė yra biologiškai ekvivalentiška suminėms dozėms, kurios buvo naudotos ankstesniuose tyrimuose. / After radical treatment of head and neck cancer 20–50% of patients are diagnosed with the locoregional recurrence during first two years. In the literature the results of studies, using reirradiation by three-dimensional radiotherapy for head and neck cancer recurrence, according to a 2-year overall survival and toxicity, are poor: overall survival reached 15.2–40%, the grade 3 - 4 toxicity reached 1.4–47% and grade 5 - 7.6%. The results of phase II and retrospective studies using the high-dose-rate brachytherapy for treatment of head and neck cancer relapse were: 2-year overall survival was 19–63%; grade 3 - 4 late toxicity 4–22.2%. In these studies 3–4 Gy per fraction up to 30–40 Gy total dose were administered. So far, the randomized study, comparing the high-dose-rate brachytherapy with the three-dimensional radiotherapy, treating head and neck cancer relapse, hasn’t been conducted. We compared different radiotherapy methods: three-dimensional conformal radiotherapy was administered to the control group (25 fractions of 2 Gy, total dose of 50 Gy); the hypofractionated high-dose-rate brachytherapy was administered to the experimental group, while applying a new regime of fractionation: 2.5 Gy per fraction, two fractions per day, up to 30 Gy total dose. Such fractionation regimen was selected in order to reduce the rate and grade of toxicity, while the total dose is biologically equivalent to the total doses, which have been used in previous studies.