No description available.

No description available.

No description available.

Spatially fractionated radiation therapy (or grid) using megavoltage x-rays is a relatively new method of treating bulky (>8 cm) malignant tumors. Unlike the conventional approach in which the entire tumor is targeted with a nearly uniform radiation field, in grid the incident radiation is collimated with a special grid collimator. As such, only the volume under the open areas of the grid receives direct irradiation from the incident beam; the rest only sees scattered radiation and hence receives significantly less dose. Those regions seeing less dose serve as regrowth areas for normal tissues, thus reducing the normal tissue complication probability after the treatment. Although the grid dose distribution in a tumor is non-uniform, the regression of tumor mass has exhibited uniform regression clinically. Protons have two advantages over megavoltage x-rays which are typically used for grid: (1) protons scatter less in tissue, and (2) they have a fixed range in tissue (the Bragg peak) that can be used to target a tumor. The goal of this thesis is to computationally and experimentally assess the feasibility of grid using clinical proton beams. The proton pencil beams at the Provision Cancer Center in Knoxville, Tennessee, are used to create an array of beams mimicking the arrangement of beams in grid therapy. The dose distributions at various depths in a solid-water phantom are obtained computationally by the Monte Carlo code MCNP and validated by RayStation experimental Gafchromic film EBT3. The results are compared with those of the grid using megavoltage x-rays.

Ο βασικός στόχος αυτής της εργασίας είναι η μελέτη της θεωρητικής συμπεριφοράς και τα πλεονεκτήματα της γενικευμένης βάθμωσης δόσης-απόκρισης, καθώς και η έρευνα για τη χρησιμότητα της γενικευμένης βάθμωσης δόσης-απόκρισης σε πρακτικά ακτινοβιολογικά πλάνα θεραπείας μέσω χρήσης της πλατφόρμας RayStation. Τέλος, θα διερευνηθεί η επίδραση της αρχιτεκτονικής του οργάνου (παράλληλη / σειριακή). Βασικό υλικό της μελέτης μας ήταν το λογισμικό για το σχεδιασμό πλάνων θεραπείας RAYSTATION 1.9, που αναπτύχθηκε και σχεδιάστηκε από τη RAYSEARCH LABORATORIES AB, Στοκχόλμη, Σουηδία. Εκτός από αυτό, κάναμε εκτεταμένη χρήση βασικών θεωρητικών τύπων που σχετίζονται με τον υπολογισμό του TCP, NTCP, P + και του γ(D) καθώς και με την ακτινοβιολογικά μοντέλα. Σε ό, τι αφορά τις μεθόδους της μελέτης αυτής, πρώτον υπολογίσαμε θεωρητικά το γ(D) για TCP και NTCP αντίστοιχα, για την ετερογενή κατανομή της δόσης σε διαφορετικά μεγέθη, προκειμένου να επαληθεύσουμε τους υπολογισμούς του RAYSTATION για TCP και NTCP. Επιπλέον, έχουμε δημιουργήσει ένα πλάνο θεραπείας με το όργανο-στόχος και τα όργανα που βρίσκονται σε κίνδυνο να βρίσκονται στην ίδια περιοχή ενδιαφέροντος, προκειμένου να ελέγξουμε την εγκυρότητα του συστήματος για την συνάρτηση P + καθώς και των γενικευμένων γ(D). Επιπλέον, έχουμε θέσει μια σειρά από διαφορετικά πλάνα θεραπείας με το όργανο-στόχος και τα όργανα σε κίνδυνο σε διαφορετικές περιοχές ενδιαφέροντος όπου αυξήσαμε τη μέση δόση, προκειμένου να διερευνήσουμε τη συμπεριφορά του ΔP(μεταβολή απόκρισης) και του γ(D), πριν και μετά την αλλαγή της δοσολογίας. Επίσης υπολογίσαμε θεωρητικά τις ποσότητες αυτές, προκειμένου να εξακριβωθεί η εγκυρότητα των θεωρητικών εκφράσεων συγκρίνοντας τες με τις τιμές που το σύστημα παρήγε σε μας. Τέλος, προσπαθήσαμε να διερευνήσουμε τη συμπεριφορά της ποσότητας ΔP υπολογίζοντας το σχετικό σφάλμα μεταξύ της πραγματικής και την κατά προσέγγιση τιμής χρησιμοποιώντας το Poisson και το Probit μοντέλο, για την περίπτωση όπου έχουμε ένα όργανο-στόχος το οποίο αποτελείται από δύο τμήματα σε παράλληλη αρχιτεκτονική και με τον ίδιο αριθμό κλώνων. Όσον αφορά τα αποτελέσματά μας, πρώτα απ 'όλα, επαληθεύσαμε θεωρητικά τους υπολογισμούς του RAYSTATION για τo γενικευμένο γ(D) και την αντικειμενική συνάρτηση με τη χρήση ενός ανεξάρτητου τρόπου υπολογισμών. Επιπλέον, αποδείχθηκε ότι μετά από μια μικρή μεταβολή (αύξηση) της δόσης, το όργανο που έχει επηρεαστεί περισσότερο, είναι το όργανο με το υψηλότερο γενικευμένο γ(D). Εκτός από αυτό, ελέγχθηκε η εγκυρότητα των θεωρητικών εκφράσεων σχετικά με τον υπολογισμό της μεταβολής της απόκρισης και του γενικευμένου γ(D), αλλά μόνο για την περίπτωση μικρής μεταβολής της δόσης. Ειδικά για την περίπτωση του 50% TCP και NTCP, οι θεωρητικές τιμές που το σύστημα παρέχει εμφανίζουν μεγάλη προσέγγιση με τις πειραματικές, γεγονός που αποδεικνύει τη μεγάλη σημασία του D50 μοντέλου στο προσδιορισμό των κλινικών επιπέδων απόκρισης. Τέλος, όσον αφορά το τελευταίο μέρος των υπολογισμών μας, μπορούμε εύκολα να πούμε ότι η συμπεριφορά της ΔPapprox εμφανίζεται λογική, διότι, για τα δύο μοντέλα που χρησιμοποιήσαμε, πλησιάζει σημαντικά την πραγματική ΔP γύρω από την περιοχή του 50% ή 37%, όπως και αναμέναμε. Επαληθεύσαμε σε αρκετά ικανοποιητικό επίπεδο κάποιες βασικές θεωρητικές προσεγγίσεις για την κλίση δόσης-απόκρισης σχετικά με τη μη ομοιόμορφη κατανομή δόσης μέσω της πλατφόρμας RayStation αλλά το πιο σημαντικό πράγμα είναι το γεγονός ότι η χρησιμότητα της των γενικευμένης βάθμωσης δόσης-απόκρισης είναι εξαιρετικά σημαντική, διότι δίνει στο σχεδιαστή των πλάνων θεραπείας τη δυνατότητα να ερευνήσει ακριβώς το όργανο το οποίο, θα επηρεαστεί περισσότερο μετά από μια μικρή αύξηση της δόσης και ως εκ τούτου θα είναι σε θέση να βελτιστοποιήσει το πλάνο για αύξηση ελέγχου του όγκου αλλά και ελαχιστοποίηση επιπλοκών των υγειών ιστών. / The basic aim of that work is the study of the theoretical behavior and merits of the Generalized Dose-Response gradient as well as the investigation of the usefulness of the generalized dose response gradient in practical radiobiological treatment planning through the use of RayStation. Last but not least, it will be investigated the influence of the organ architecture(parallel/serial). Basic material of our study was the treatment planning platform RAYSTATION 1.9 that was developed and designed by RAYSEARCH LABORATORIES AB,STOCKHOLM,SWEDEN. Except for that ,we made extensive use of basic theoretical formulas that are related to the calculation of TCP, NTCP, P+ and Generalized Gamma as well as to the radiobiological models. As far as the methods of that study are concerned, firstly we calculated theoretically the Generalized Gamma for TCP and NTCP respectively, for heterogeneous dose distribution to different volumes in order to verify RAYSTATION computations for TCP and NTCP. Furthermore, we set a treatment plan with the target organ and the organs at risk in the same ROI in order to check the validity of the system concerning the objective function P+ and the Generalized Gamma. Moreover ,we set a number of different treatment plans with the target organ and the organs at risk in different ROIs and we increased the mean dose in order to investigate the behavior of change in response and that of γ(D) ,before and after the change in dose and to calculate theoretically these quantities, in order to verify the validity of the theoretical expressions by comparing them with the values that the system is providing to us. Finally, we tried to investigate the behavior of ΔP by calculating the relative error between the real and the approximate value using the Poisson and the Probit model, for the case of having a target organ consisting of two compartments in a parallel architecture and with the same number of clonogens. Concerning our results, first of all, we verified theoretically the computations of the RAYSTATION about the Generalized Gamma and the objective function by using an independent way of calculations. Furthermore, we proved that after a small change (increase) in dose ,the organ that is being affected most ,is the organ with the highest Generalized Gamma. Except for that, we verified the validity of the theoretical expressions concerning the calculation of the change in response and that of Generalized Gamma but only for the case of small change in dose. Especially for the case of 50% TCP and NTCP, the theoretical and the values that the system is providing appear great approximation, a fact that proves the high importance of D50 model in specifying clinical response levels. Finally, concerning the last part of our calculations, we easily can say that the behavior of ΔPapprox looks sensible because, for both models that we used, it approaches significantly the real ΔP around the region of 50% or 37% response, as we were expecting. We verified in a quite satisfying level some basic theoretical approaches for dose-response gradient concerning the non-uniform dose delivery through the RayStation platform but the most important thing is the fact that the usefulness of the of the Generalized Dose response gradient is extremely important because it gives to the planner the opportunity to investigate precisely which organ, from the normal tissues will be affected most after a small increase in dose and as a result he will be able to optimize the plan for higher tumor control and lowest normal tissue complications. *This work had been done in collaboration with the Division of Medical Radiation Physics, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden

No description available.

Deformable image registration (DIR) is a type of registration that calculates a deformable vector field (DVF) between two image data sets and permits contour and dose propagation. However the calculation of a DVF is considered an ill-posed problem, as there is no exact solution to a deformation problem, therefore all DVFs calculated contain errors. As a result it is important to evaluate and assess the accuracy and limitations of any DIR algorithm intended for clinical use. The influence of image quality on the DIR algorithms performance was also evaluated. The hybrid DIR algorithm in RayStation 4.0.1.4 was assessed using a number of evaluation methods and data. The evaluation methods were point of interest (POI) propagation, contour propagation and dose measurements. The data types used were phantom and patient data. A number of metrics were used for quantitative analysis and visual inspection was used for qualitative analysis. The quantitative and qualitative results indicated that all DVFs calculated by the DIR algorithm contained errors which translated into errors in the propagated contours and propagated dose. The results showed that the errors were largest for small contour volumes (<20cm3) and for large anatomical volume changes between the image sets, which pushes the algorithms ability to deform, a significant decrease in accuracy was observed for anatomical volume changes of greater than 10%. When the propagated contours in the head and neck were used for planning the errors in the DVF were found to cause under dosing to the target tumour by up to 32% and over dosing to the organs at risk (OAR) by up to 12% which is clinically significant. The results also indicated that the image quality does not have a significant effect on the DIR algorithms calculations. Dose measurements indicated errors in the DVF calculations that could potentially be clinically significant. The results indicate that contour propagation and dose propagation must be used with caution if clinical use is intended. For clinical use contour propagation requires evaluation of every propagated contour by an expert user and dose propagation requires thorough evaluation of the DVF.

No description available.

Cancer is the second largest mortal disease in Sweden, and high efforts are made to develop the treatment of cancer. One of the main treatment methods is radiotherapy, which uses ionizing radiation to damage the cancerous cells. This has the chance of stopping the cell reproduction, and the goal is to reduce the tumor and stop the tumor growth. The most common forms of radiotherapy uses external beams to irradiate the tumor. In intensity modulated radiotherapy, IMRT, the beam fluences are optimized to give a highly conformal dose, i.e. a dose distribution which is restricted to the tumor and has low dose values outside of the tumor. A conformal dose is necessary to spare healthy tissue and sensitive organs, and thus keep the side-effects of the treatment at an acceptable level. The optimized beam shapes are created using a multileaf collimator, MLC. Finding the leaf positions and dose levels is formulated as a problem in the framework of mathematical optimization. Currently, one of the limitations in delivering conformal dose is due to patient movement during the treatment. In IMRT, the beams are delivered by consecutive segments, and the exact pairing of the segments with the patient position will have an impact on the delivered dose. This is called the interplay effect, and can cause both underdosage of the tumor and overdosage of the surrounding tissue. There are methods of mitigating the interplay effect. For example, the beam could be restricted to a single phase of the motion by repeatedly turning it on and off. This is known as gating. However, gating and many other interplay mitigation techniques lead to prolonged treatment times, which decreases the clinical throughput, causes higher patient discomfort and gives higher uncertainties in the delivered dose. This makes it desirable to find methods which avoid prolonged treatment times, while still giving highly conformal doses. Ideally, the best method would be to have a beam which follows any target movement. This idea is known as target tracking. In this thesis, an optimization method is suggested which includes the interplay effect in the treatment optimization. Two main treatment strategies are proposed. The method which is simplest to implement clinically is to create plans which are robust against uncertainties in the times for the patient motion. The resulting doses are found to give acceptable target covering where similar, conventional plans give a significant target underdose. To further increase the conformality of the doses, a non-robust method paired with gating technology is suggested. This method can effectively be seen as a target tracking method, and has the possibility to give highly conformal doses under acceptable treatment times.