<p>On-board imaging is useful for guiding radiation to patients in the treatment position; however, current treatment-room imaging modalities are not sensitive to physiology - features that may differentiate tumor from nearby tissue or identify biological targets, e.g., hypoxia, high tumor burden, or increased proliferation. Single photon emission computed tomography (SPECT) is sensitive to physiology. We propose on-board SPECT for biological target localization.</p><p>Localization performance was studied in computer-simulated and scanner-acquired parallel-hole SPECT images. Numerical observers were forced to localize hot targets in limited search volumes that account for uncertainties common to radiation therapy delivery. Localization performance was studied for spherical targets of various diameters, activity ratios, and anatomical locations. Also investigated were the effects of detector response function compensation (DRC) and observer normalization on target localization. Localization performance was optimized as a function of iteration number and degree of post-reconstruction smoothing. Localization error patterns were analyzed for directional dependencies and were related to the detector trajectory. Localization performance and the effect of the detector trajectory were investigated in a hardware study using a whole-body phantom.</p><p>Typically targets of 6:1 activity were localized as accurately using 4-minute scans as those of 3:1 activity using 20-minute scans. This trend is consistent with the relationship between contrast and noise in the contrast-to-noise ratio (CNR) and implies that higher contrast targets are better candidates for on-board SPECT because of time constraints in the treatment room. Using 4-minute scans, mean localization errors were within 2 mm for superficial targets of 6:1 activity that were proximal to the detector trajectory and of at least 14 mm in diameter. Localization was significantly better (p < 0.05, Wilcoxon signed-rank test) with than without observer normalization and DRC at 5 of 6 superficial tumor sites. Observer normalization improved localization substantially for a target proximal to the much hotter heart. Localization error patterns were shown to be anisotropic and dependent on target position relative to the detector trajectory. Detector views of close approach and of minimal attenuation were predictive of directions with the smallest (magnitude) localization bias and precision. The detector trajectory had a substantial effect on localization performance. In scanner-acquired SPECT images, mean localization errors of a 22-mm-diameter superficial target were 0.8, 1.5, and 6.9 mm respectively using proximal 180°, 360°, and distal 180° detector trajectories, thus demonstrating the benefits of using a proximal 180° detector trajectory.</p><p>In conclusion, the potential performance characteristics of on-board SPECT were investigated using computer-simulation and real-detector studies. Mean localization errors < 2 mm were obtained for proximal, superficial targets with diameters >14 mm and of 6:1 activity relative to background using scan times of approximately 5 minutes. The observed direction-dependent localization errors are related to the detector trajectory and have important implications for radiation therapy. This works shows that parallel-hole SPECT could be useful for localizing certain biological targets.</p> / Dissertation

<p>Imaging respiratory induced tumor motion in the radiation therapy treatment room could eliminate the necessity for large motion encompassing margins that result in excessive irradiation of healthy tissues. Currently available image guidance technologies are ill-suited for this task. Two-dimensional fluoroscopic images are acquired with sufficient speed to image respiratory motion. However, volume information is not present, and soft tissue structures are often not visible because a large volume is projected onto a single plane. Currently available volumetric imaging modalities are not acquired with sufficient speed to capture full motion trajectory information. Four-dimensional cone-beam computed tomography (4D CBCT) using a gantry mounted 2D flat panel imaging device has been proposed but has been limited by high doses, long scan times and severe under-sampling artifacts. The focus of the work completed in this thesis was to find ways to improve 4D imaging using a gantry mounted 2D kV imaging system. Specifically, the goals were to investigate methods for minimizing imaging dose and scan time while achieving consistent, controllable, high quality 4D images.</p><p>First, we introduced four-dimensional digital tomosynthesis (4D DTS) and characterized its potential for 3D motion analysis using a motion phantom. The motion phantom was programmed to exhibit motion profiles with various known amplitudes in all three dimensions and scanned using a 2D kV imaging system mounted on a linear accelerator. Two arcs of projection data centered about the anterior-posterior and lateral axes were used to reconstruct phase resolved DTS coronal and sagittal images. Respiratory signals were obtained by analyzing projection data, and these signals were used to derive phases for each of the projection images. Projection images were sorted according to phase, and DTS phase images were reconstructed for each phase bin. 4D DTS target location accuracies for peak inhalation and peak exhalation in all three dimensions were limited only by the 0.5 mm pixel resolution for all DTS scan angles. The average localization errors for all phases of an assymetric motion profile with a 2 cm peak-to-peak amplitude were 0.68, 0.67 and 1.85 mm for 60 <super> o <super/> 4D DTS, 360<super> o <super/> CBCT and 4DCT, respectively. Motion artifacts for 4D DTS were found to be substantially less than those seen in 4DCT, which is the current clinical standard in 4D imaging. </p><p>We then developed a comprehensive framework for relating patient respiratory parameters with acquisition and reconstruction parameters for slow gantry rotation 4D DTS and 4D CBCT imaging. This framework was validated and optimized with phantom and lung patient studies. The framework facilitates calculation of optimal frame rates and gantry rotation speeds based on patient specific respiratory parameters and required temporal resolution (task dependent). We also conducted lung patient studies to investigate required scan angles for 4D DTS and achievable dose and scan times for 4D DTS and 4D CBCT using the optimized framework. This explicit and comprehensive framework of relationships allowed us to demonstrate that under-sampling artifacts can be controlled, and 4D CBCT images can be acquired using lower doses than previously reported. We reconstructed 4D CBCT images of three patients with accumulated doses of 4.8 to 5.7 cGy. These doses are three times less than the doses used for the only previously reported 4D CBCT investigation that did not report images characterized by severe under-sampling artifacts. </p><p>We found that scan times for 200<super> o <super/> 4D CBCT imaging using acquisition sequences optimized for reduction of imaging dose and under-sampling artifacts were necessarily between 4 and 7 minutes (depending on patient respiration). The results from lung patient studies concluded that scan times could be reduced using 4D DTS. Patient 4D DTS studies demonstrated that tumor visibility for the lung patients we studied could be achieved using 30<super> o <super/> scan angles for coronal views. Scan times for those cases were between 41 and 50 seconds. Additional dose reductions were also demonstrated. Image doses were between 1.56 and 2.13 cGy. These doses are well below doses for standard CBCT scans. The techniques developed and reported in this thesis demonstrate how respiratory motion can be imaged in the radiotherapy treatment room using clinically feasible imaging doses and scan times.</p> / Dissertation

No description available.

In-beam Positron Emission Tomography (PET) is a system for monitoring high precision radiation therapy which is in the most cases applied to the tumors near organs at risk. High quality and fast availability of in-beam PET images are, therefore, extremely important for successful verification of the dose delivery. Two main problems make an in-beam PET monitoring a challenging task. Firstly, in-beam PET measurements result in a very low counting statistics. Secondly, an integration of the PET scanner into the treatment facility requires significant reduction of the sensitive surface of the scanner and leads to a dual-head form resulting in imaging artifacts. The aim of this work is to bring the imaging process by means of in-beam PET to optimum quality and time scale. The following topics are under consideration: - analysis of image quality for in-beam PET; - image reconstruction; - solutions for building, testing, and integration of a PET monitoring system into the dedicated treatment facility.

Despite the common usage of high-dose vitamin C among breast cancer patients, the published medical literature is not in agreement as to how mega-dose vitamin C may interact with conventional therapy to affect clinical outcomes. The purpose of this study was to investigate the interaction of mega-dose vitamin C with radiation therapy and with doxorubicin in the treatment of breast cancer. Cultures of EMT6 mouse mammary tumor cells were treated concurrently with varying dose of vitamin C and either radiation or doxorubicin. A clonogenic assay was then performed to determine the surviving fraction of the cells. The surviving fractions of cells in cultures receiving different doses of vitamin C were compared among themselves as well as with controls and dose response curves were generated. Results show that ascorbic acid administered in concentrations of 1 mM or 10 mM 4 hours before x-irradiation protected the cells from radiation-induced cytotoxicity. The dose-modifying factors for 1 mM and 10 mM ascorbic acid as compared to controls were 1.23 and 1.37 respectively. These results support the hypothesis that mega dose vitamin C, when taken concurrently with radiation therapy, protects cancer cells from the cytotoxic effects of ionizing radiation. No evidence was found to suggest that mega-dose vitamin C alters the antineoplastic effects of doxorubicin.

<p>Electron beam therapy represents an underutilized area in radiation therapy. While electron radiation therapy has existed for many decades and electron beams with multiple energies are available on linear accelerators – the most common device to deliver radiation therapy – efforts to advance the field have been slow. In contrast, photon beam therapy has seen rapid advancements in the past decade, and has become the main modality for radiation therapy treatment. </p><p>This doctoral research project comprises the development of a novel treatment modality, dynamic electron arc radiotherapy (DEAR) that seeks to address challenges to clinical implementation of electron beam therapy by providing a technique that may be able to treat specific patient subsets with better outcomes than current techniques. This research not only focused on the development of DEAR, but also aimed to improve upon and introduce new tools and techniques that could translate to current clinical electron beam therapy practice. </p><p>The concept of DEAR is presented. DEAR represents a new conformal electron therapy technique with synchronized couch motion. DEAR utilizes the combination of gantry rotation, couch motion, and dose rate modulation to achieve desirable dose distributions in patient. The electron applicator is kept to minimize scatter and maintain narrow penumbra. The couch motion is synchronized with the gantry rotation to avoid collision between patient and the electron cone. </p><p>First, the feasibility of DEAR delivery was investigated and the potential of DEAR was demonstrated to improve dose distributions on simple cylindrical phantoms. DEAR was delivered on Varian’s TrueBeam linac in Research Mode. In conjunction with the recorded trajectory log files, mechanical motion accuracies and dose rate modulation precision were analyzed. Experimental and calculated dose distributions were investigated for a few selected energies (6 MeV and 9 MeV) and cut-out sizes (1x10 cm2 and 3x10 cm2 for a 15x15 cm2 applicator). Our findings show that DEAR delivery is feasible and has the potential to deliver radiation dose with high precision (RMSE of <0.1 MU, <0.1° gantry, and <0.1 cm couch positions) and good dose rate precision (1.6 MU/min). Dose homogeneity within ±2 % in large and curved targets can be achieved while comparable penumbra to a standard electron beam on a flat surface can be maintained. Further, DEAR does not require fabrication of patient-specific shields, which has hindered the widespread use of electron arc therapy. These benefits make DEAR a promising technique for conformal radiotherapy of superficial tumors.</p><p>Next, an accurate dose calculation framework for DEAR was developed since current commercial dose calculation systems cannot handle the dynamic nature of the DEAR. Comprehensive validations of vendor provided electron beam phase space files for Varian TrueBeam linacs against measurement data were assessed. In this framework, the Monte Carlo generated phase space files were provided by the vendor and used as input to the downstream plan-specific simulations including jaws, electron applicators, and water phantom computed in the EGSnrc environment. The phase space files were generated based on open field commissioning data. A subset of electron energies of 6, 9, 12, 16, and 20 MeV and open and collimated field sizes 3×3, 4×4, 5×5, 6×6, 10×10, 15×15, 20×20, and 25×25 cm2 were evaluated. Measurements acquired with a CC13 cylindrical ionization chamber and electron diode detector and simulations from this framework were compared for a water phantom geometry. The evaluation metrics include percent depth dose, orthogonal and diagonal profiles at depths R100, R50, Rp, and Rp+ for standard and extended source-to-surface distances (SSD), as well as cone and cut-out output factors. Agreement for the percent depth dose and orthogonal profiles between measurement and Monte Carlo were generally within 2% or 1 mm. The largest discrepancies were observed for depths within 5 mm from the phantom surface. Differences in field size, penumbra, and flatness for the orthogonal profiles at depths R100, R50, Rp, and Rp+ were within 1 mm, 1 mm, and 2%, respectively. Simulated and measured orthogonal profiles at SSDs of 100 and 120 cm showed the same level of agreement. Cone and cut-out output factors agreed well with maximum differences within 2.5% for 6 MeV and 1% for all other energies. Cone output factors at extended SSDs of 105, 110, 115, and 120 cm exhibited similar levels of agreement. The presented Monte Carlo simulation framework for electron beam dose calculations for Varian TrueBeam linacs for electron beam energies of 6 to 20 MeV for open and collimated field sizes from 3×3 to 25×25 cm2 were studied and results were compared to the measurement data with excellent agreement. </p><p>DEAR uses the superposition of many small fields for its delivery, as such accurate planning requires the knowledge of accurate small field dosimetry. Prior research has shown that previous versions of the clinically used eMC dose calculation algorithm (Varian Medical Systems, Inc., Palo Alto, CA) cannot accurately calculate small static electron fields, leading to discrepancies in the dose distributions and output. Further, the clinical treatment planning system, Eclipse, currently does not support the planning of dynamic electron radiation therapy. Therefore, the aforementioned validation was extended to small fields and compared to dose calculations from the treatment planning system.</p><p>Subsequently, small field optimization was explored. Monte Carlo simulations were performed using validated Varian TrueBeam phase space files for electron beam energies of 6, 9, 12, and 16 MeV and square (1x1, 2x2, 3x3, 4x4, and 5x5 cm2) and circular (1, 2, 3, 4, and 5 cm diameter) fields. Resulting dose distributions (kernels) were used for subsequent calculations. The following analyses were performed: (1) Comparison of composite square fields and reference 10x10 cm2 dose distributions and (2) Scanning beam deliveries for square and circular fields realized as the convolution of kernels and scanning pattern. Preliminary beam weight and pattern optimization were also performed. Two linear scans of 10 cm with/without overlap were modeled. Comparison metrics included depth and orthogonal profiles at dmax. (1) Composite fields regained reference depth dose profiles for most energies and fields within 5%. Smaller kernels and higher energies increased dose in the build-up and Bremsstrahlung region (30%, 16 MeV and 1x1 cm2), while reference dmax was maintained for all energies and composite fields. Smaller kernels (<2x2 cm2) maintained penumbra and field size within 0.2 cm, and flatness within 2 and 4% in the cross-plane and in-plane direction, respectively. Deterioration of penumbra for larger kernels (5x5 cm2) was observed. Balancing desirable dosimetry and efficiencies suggests that smaller kernels should be used at the target edges and larger kernels in the center of the target. (2) Beam weight optimization improves cross-plane penumbra (0.2 cm) and increases the field size (0.4 cm) on average. In-plane penumbra and field size remain unchanged. Overlap depends on kernel size and optimal overlap results in flatness ±2%. Dynamic electron beam therapy in virtual scanning mode is feasible by employing small fields to achieve desired dose distributions and acceptable efficiencies.</p><p>Further, tools to generally improve upon limitations in Monte Carlo simulations for electron beams were investigated. The phase space file contains a finite number of particle histories and can have very large file size, yet still contains inherent statistical noises. A characterization of the phase space file was investigated to overcome its inherent limitations. To characterize the phase space file, distributions for energy, position, and direction of all particles types were analyzed as piece-wise parameterized functions of radius. Subsequently, a pseudo phase space file was generated based on this characterization. Validation was assessed by directly comparing the original and pseudo phase space file, and by comparing the resulting dose distributions from Monte Carlo simulations using both phase space files. Monte Carlo simulations were run for energies 6, 9, 12, and 16 MeV and all standard field sizes 6x6, 10x10, 15x15, 20x20, and 25x25 cm2. Percent depth dose and orthogonal profiles at depths R100, R50, and Rp were evaluated. Histograms of the original and pseudo phase space file agree very well with correlation coefficients greater than 0.98 for all particle attributes. Dosimetric comparison between original and pseudo dose distributions yielded agreement within 2%/1mm for PDDs and profiles at all depths for all field sizes 6x6, 10x10, 15x15, 20x20, and 25x25 cm2 and energies 6, 9, 12, and 16 MeV. Phase space files were found to be successfully characterized by piece-wise distributions for energy, position, and direction as parameterized functions of radius and polar angle. This facilitates generation of sufficient particles at any statistical precisions.</p><p>Additionally, new hardware for improved DEAR capability was investigated. Few leaf electron collimators (FLEC) or electron MLCs (eMLC) are highly desirable for dynamic electron beam therapies as they produce multiple apertures within a single delivery to achieve conformal dose distributions. However, their clinical implementation has been challenging. Alternatively, multiple small apertures in a single cut-out with variable jaw sizes could be utilized in a single dynamic delivery. A Monte Carlo simulation study was performed to investigate the dosimetric characteristics of such an arrangement. Investigated quantities included: Energy (6 and 16 MeV), jaw size (1x1 to 22x22 cm2; centered to aperture), applicator/cut-out (15x15 cm2), aperture (1x1, 2x2, 3x3, and 4x4 cm2), and aperture placement (on/off central axis). Three configurations were assessed: (a) single aperture on-axis, (b) single aperture off-axis, and (c) multiple apertures. Reference was configuration (a) with the standard jaw size. Aperture placement and jaw size were optimized to maintain reference dosimetry and minimize leakage through unused apertures to <5%. Comparison metrics included depth dose and orthogonal profiles. Configuration (a) and (b): Jaw openings were reduced to 10x10 cm2 without affecting dosimetry (gamma 2%/1mm) regardless of on- or off-axis placement. For smaller jaw sizes, reduced surface (<2%, 5% for 1x1 cm2 aperture) and increased Bremsstrahlung (<2%, 10% for 1x1 cm2 aperture) dose was observed. Configuration (c): Optimal aperture placement was in the corners (order: 1x1, 4x4, 2x2, 3x3 cm2 for quadrants I, II, III, and IV) and jaw size were 2x2, 2x2, 3x3, and 7x7 cm2 and 7x7, 7x7, 10x10, and 10x10 cm2 for apertures: 1x1, 2x2, 3x3, 4x4 cm2 and energies 6 and 16 MeV, respectively. Asymmetric leakage was found from upper and lower jaws. Leakage was generally within 5% with a maximum of 10% observed for the 1x1 cm2 aperture irradiation. Multiple apertures in a single cut-out with variable jaw size can be used in a single dynamic delivery, thus providing a practical alternative to FLEC or eMLC.</p><p>Based on all the results from this project, DEAR has been found to be a feasible technique and demonstrates the potential to improve electron therapy.</p> / Dissertation

Microbeam radiation therapy (MRT) is a potential cancer therapy technique that uses an intense X-ray beam produced by a synchrotron. In MRT, an array of microplanar beams, called a microbeam, is delivered to a tumour. The dose at each centre of planar beams is extremely large (several hundred grays) while dose level in the valley between the peaks is below several tens of gray. Moreover, the width of each planar beam is typically 20 - 50 µm, and the distance from a centre of planar-beam to that of adjacent beam is 200 - 400 µm. For the latter reasons, the fundamental requirements for the dosimetry technique in MRT are (1) a micrometer-scale spatial resolution and (2) detection sensitivity at large doses (5 - 1000 Gy). No existing detectors can satisfy those two requirements together. The objective of the Ph.D. research is to develop a prototype dosimetry technique which fulfils the requirements for measuring the dose profile in the microbeam. The currently used approach relies on the indirect detection of X-rays; in which the X-ray dose is recorded on a detector plate, and then the recorded signals are digitized using a reader. Our proposed approach utilizes Sm3+-doped polycrystallites, glasses, and/or suitable glass-ceramics (though our approach is not limited to the use of Sm ion) for the detector plate, in which a valence reduction of Sm3+, that is the conversion of Sm3+ to Sm2+, takes place upon irradiation of X-rays. The extent of reduction is further read out using confocal fluorescence microscopy via the photoluminescence (PL) signals of Sm3+ and Sm2+. The work carried out throughout the course of the research includes the construction of confocal fluorescence microscopy, synthesis and characterizations of dosimeter materials, as well as application tests of our approach for measuring the dose profile of a microbeam used at synchrotron facilities -- Canadian Light Source (CLS), Saskatoon, Canada, European Synchrotron Radiation Facility (ESRF), Grenoble, France, and SPring-8, Hyogo, Japan. Further, the research has shown that 1 % Sm-doped fluoroaluminate glass is one of the best candidates for the type of dosimetric application. It has the dynamic range of ~1 to over 1000 Gy which covers the dose range used in MRT, excellent signal-to-noise ratio (large extent of Sm3+ → Sm2+ change), and excellent stability of recorded signal over time. The recorded signal in the detector is erasable by heating or exposing to light such as UV. Furthermore, with a use of confocal microscope, it has ability to measure the distribution pattern of dose over the cross-section of microbeam. Therefore, we believe that our approach is one of the most promising techniques available.

Στόχος τη ακτινοθεραπείας είναι η χορήγηση της θεραπευτικής δόσης με τη μέγιστη δυνατή ακρίβεια. Αυτό συνεπάγεται τον σωστό καθορισμό της ακτινοβολούμενης περιοχής καθώς και την ακριβή εναπόθεση της δόσης. Αυτή η διπλωματική εργασία ασχολείται με την προσπάθεια για ακριβή υπολογισμό και εναπόθεση της δόσης για πεδία ακτινοβόλησης τα όποια είναι μικρότερα από 5x5cm. Όταν το μέγεθος του πεδίου μικρύνει τότε η μέτρηση και ο υπολογισμός της δόσης με κλασικές μεθόδους δε είναι πλέον ακριβείς καθώς παράγοντες όπως η πλευρική ηλεκτρονική ισορροπία, το μέγεθος και είδος του ανιχνευτή καθώς και το μέγεθος της πηγής που είναι ορατό από κάθε σημείο, πρέπει να ληφθούν υπόψη. Στη παρούσα εργασία χρησιμοποιήθηκε το λογισμικό Mephysto για να μετρήσουμε την πραγματική δόση που δίνει ο γραμμικός επιταχυντής της εταιρείας ELEKTA σε δέσμες φωτονίων ενέργειας 6 ΜV χρησιμοποιώντας έναν ανιχνευτή Pin Point της εταιρείας PTW. Στη συνέχεια συγκρίθηκαν αυτά τα αποτελέσματα (προφίλ δόσης, κατά βάθος δόση PDD) με τα αποτελέσματα που δοθήκαν από το υπολογιστικό σύστημα σχεδιασμού θεραπειών (Treatment Planning System) Oncentra Master Plan της εταιρείας Nucletron. Παρατηρήθηκε απόκλιση μεταξύ αυτών των δυο μεθόδων ελαφρώς μικρότερη του 3%. Αυτή η απόκλιση οφείλεται στο ότι ο εικονικός γραμμικός επιταχυντής που έχει δημιουργηθεί στο σύστημα Oncentra Master Plan για τον υπολογισμό της δόσης, δημιουργήθηκε ώστε να αποδίδει πλησιέστερα αποτελέσματα σε αυτά του ELEKTA για πεδία ακτινοβόλησης που έχουν μεγάλη κλινική χρήση (5 έως 15 cm αν διάσταση). Όταν όμως τα πεδία μικρύνουν (κάτω από 5cm αν διάσταση) τότε έχουμε απόκλιση από της πραγματικές τιμές. Αλλάζοντας το φαινομενικό μέγεθος της πηγής στο Oncentra Master Plan καταφέραμε να φέρουμε τους υπολογισμούς από το Oncentra Master Plan πάρα πολύ κοντά στις μετρήσεις του Mephysto. Δημιουργήθηκε έτσι ένα νέο εικονικό μηχάνημα στη βάση δεδομένων του Oncentra Master Plan με το όνομα Sli Patras SRS, οι παράμετροι του οποίου (φαινομενικό μέγεθος πηγής) έχουν βελτιστοποιηθεί για ακριβέστερους υπολογισμούς δόσης για μικρά πεδία. Με αυτό το μηχάνημα καταφέρθηκε ακριβέστερος υπολογισμός της δόσης, με αποκλίσεις μικρότερες από 1.5%, για μικρά πεδία, σε σύγκριση με το προηγούμενο μηχάνημα Sli Patra. Το νέο αυτό μηχάνημα επιτρέπει ακριβέστερους υπολογισμούς για μικρά πεδία και έχει πλέον υιοθετηθεί και χρησιμοποιείται στην κλινική ρουτίνα στο Π.Γ.Ν. Πατρών. / Small field dosimetry in sterotactic cancer radiation therapy.

Σκοπός της ακτινοθεραπείας του μαστού μετά το χειρουργείο είναι να μειωθεί η πιθανότητα της τοπικής επανεμφάνισης της νόσου παρέχοντας ταυτόχρονα κατά το δυνατό μία ανώτερη αισθητική στον μαστό. Ο στόχος αυτός μπορεί να επιτευχθεί με να δοθεί η κατά το δυνατό μέγιστη δόση σε ολόκληρο το μαστό ενώ ταυτόχρονα η δόση στα γειτονικά από το μαστό όργανα (πνεύμονας, καρδιά και ο δίπλα μαστός) να είναι η μικρότερη δυνατή. Ως εκ τούτου, είναι πολύ σημαντική η ακριβής καθημερινή τοποθέτηση της ασθενούς σε θέση θεραπείας καθώς ακόμη και μικρές αποκλίσεις από την προτιθέμενη τοποθέτηση μπορεί να έχει σημαντικές δοσιμετρικές συνέπειες. Αλλαγές στη δοσιμετρία έχουν σημαντικές συνέπειες στην καλή κάλυψη του όγκου στόχου άρα και στην πιθανότητα ελέγχου του όγκου. Τα γεωμετρικά λάθη εμφανίζονται σαν αποκλίσεις μεταξύ της γεωμετρίας που επιθυμείτε να εφαρμοστεί σύμφωνα με το πλάνο της θεραπείας και της πραγματικής γεωμετρίας που εφαρμόζεται κατά την θεραπεία. Tα συστηματικά λάθη παριστάνουν την διαφορά μεταξύ του επιθυμητού πλάνου θεραπείας και του πλάνου που εφαρμόζεται ενώ οι αποκλίσεις που εμφανίζονται μεταξύ των συνεδριών αφορούν τα τυχαία λάθη. Οι αποκλίσεις αυτές μετρώνται καθημερινά με ένα σύστημα ηλεκτρονικής κινητής απεικόνισης και εν συνεχεία με κατάλληλη μέθοδο προβλέπονται, ελαχιστοποιούνται και ελέγχονται. Στην παρούσα εργασία σκοπός ήταν να μετρηθούν τα γεωμετρικά λάθη που εμφανίζονται κατά την τοποθέτηση της ασθενούς και να εκτιμηθεί η μεταβολή στη δόση που προκύπτει και οφείλεται στα λάθη της τοποθέτησης και ταυτόχρονα να εξαχθούν από τις μεταβολές αυτές φυσικές και βιολογικές παράμετροι. / The aim of breast radiotherapy after surgery is to reduce the probability of local recurrence while providing a superior breast cosmesis. The main purpose of radiotherapy is to give the maximum prescribed dose to the whole breast while at the same time minimizing the dose to the organs placed at the vicinity of breast (lung, heart, contralateral breast). Therefore, accuracy of daily set up for treatments is important because small spatial deviations from the intended set up may have important dosimetric consequences. Changes in dosimetry have implications for coverage of the target volume and hence for tumor control probability. Geometrical errors are presented as deviation between intended geometry of radiotherapy plan and real geometry of radiotherapy treatment. . Total set up error consists of systematic (Σ set up) and random component (σ set up). Systematic errors represent the recurring difference between intended and actual geometry while fraction-to-fraction variations are called random errors. Errors’ measuring for patients undergoing breast radiotherapy with electronic portal imaging device and afterwards a proper correction strategy enables to predict, minimize, and keep under control the amount for most of geometrical errors. The aim of this work was to determine these geometrical uncertainties and to evaluate dose perturbation due to setup error in tangential breast irradiation and as well as extract physical and biological parameters.

The goal of radiotherapy is to operate within the therapeutic window - delivering doses of ionizing radiation to achieve locoregional tumour control, while minimizing normal tissue toxicity. A greater therapeutic ratio can be achieved by utilizing radiosensitizing agents designed to enhance the effects of radiation at the tumour. Gold nanoparticles (AuNP) represent a novel radiosensitizer with unique and attractive properties. AuNPs enhance local photon interactions, thereby converting photons into localized damaging electrons. Experimental reports of AuNP radiosensitization reveal this enhancement effect to be highly sensitive to irradiation source energy, cell line, and AuNP size, concentration and intracellular localization. This thesis explored the physics and some of the underlying mechanisms behind AuNP radiosensitization. A Monte Carlo simulation approach was developed to investigate the enhanced photoelectric absorption within AuNPs, and to characterize the escaping energy and range of the photoelectric products. Simulations revealed a 10^3 fold increase in the rate of photoelectric absorption using low-energy brachytherapy sources compared to megavolt sources. For low-energy sources, AuNPs released electrons with ranges of only a few microns in the surrounding tissue. For higher energy sources, longer ranged photoelectric products travelled orders of magnitude farther. A novel radiobiological model called the AuNP radiosensitization predictive (ARP) model was developed based on the unique nanoscale energy deposition pattern around AuNPs. The ARP model incorporated detailed Monte Carlo simulations with experimentally determined parameters to predict AuNP radiosensitization. This model compared well to in vitro experiments involving two cancer cell lines (PC-3 and SK-BR-3), two AuNP sizes (5 and 30 nm) and two source energies (100 and 300 kVp). The ARP model was then used to explore the effects of AuNP intracellular localization using 1.9 and 100 nm AuNPs, and 100 and 300 kVp source energies. The impact of AuNP localization was most significant for low-energy sources. At equal mass concentrations, AuNP size did not impact radiosensitization unless the AuNPs were localized in the nucleus. This novel predictive model of AuNP radiosensitization could help define the optimal use of AuNPs in potential clinical strategies by determining therapeutic AuNP concentrations, and recommending when active approaches to cellular accumulation are most beneficial.