"In radiation therapy, trajectory-based delivery involves the dynamic motion of linear accelerator components combined with continuous arc radiation delivery. The increased complexity of the delivery may yield dosimetric advantages, but the delivery technique has not seen clinical implementation. The purpose of this thesis work is to provide support for clinical implementation of trajectory-based treatment delivery, through the application of novel trajectories, implementation of a trajectory-based optimization algorithm, and verification of the treatment delivery accuracy under dynamic conditions.The initial study in this thesis applied translational couch trajectories to reduce the effective source-to-axis distance (SAD), with potential benefits due to the decreased projected size of the multileaf collimator and an increased effective dose rate. A noncoplanar trajectory was applied to patients presented with cranial targets, and treatment plans were optimized at shortened and standard SAD. Through comparisons to clinical treatment plans, the shortened SAD treatment plans yielded a fraction size dependent decrease in the treatment delivery time due to the increased effective dose rate. The noncoplanar trajectories yielded comparable plan quality to the clinical deliveries.The next study focused on the novel implementation of a trajectory optimization algorithm for concurrent gantry and couch rotation. The optimization algorithm implemented uses the column generation approach to simultaneously determine the trajectory path during volumetric modulated arc therapy optimization (simTr-VMAT). With comparisons to coplanar VMAT plans and to randomly generated trajectories that represent the solution space for the optimization problem, the simTr-VMAT optimization methodology was validated.The complex trajectory paths resulting from the simTr-VMAT optimizations were observed as a potential source of dose delivery inaccuracy. A trajectory smoothing procedure was implemented, and the base and smoothed treatment plans were delivered on the TrueBeam linear accelerator. The trajectory smoothing retained the treatment plan quality of the base trajectories. The delivery accuracy was largely within combined standard uncertainty. A systematic difference between measurement and calculation was observed that requires further investigation. The smoothed trajectory plans yielded improved agreement with measurement compared to the base trajectory plans.The final study investigated the gantry-couch rotation angle coordinate system. Trajectory optimizations were performed under a cartesian and spherical coordinate system for seven patient cases, using a overlap score map approach. The arclength between adjacent control points showed less variation for cases where the cartesian trajectory included arc segments with couch-only rotations. The objective function value was improved for 4 out of 7 patient cases for the spherical trajectories, but limitations of two-step trajectory optimization approaches were observed.Through the research presented in this thesis, clinical advantages of trajectory-based delivery were demonstrated, as well as the importance of trajectory smoothing to improve the accuracy of dose delivery. This work helps to pave the way towards the clinical implementation of trajectory-based treatment delivery"--

The six volumes LNCS 11619-11624 constitute the refereed proceedings of the 19th International Conference on Computational Science and Its Applications, ICCSA 2019, held in Saint Petersburg, Russia, in July 2019. The 64 full papers, 10 short papers and 259 workshop papers presented were carefully reviewed and selected form numerous submissions. The 64 full papers are organized in the following five general tracks: computational methods, algorithms and scientific applications; high performance computing and networks; geometric modeling, graphics and visualization; advanced and emerging applications; and information systems and technologies. The 259 workshop papers were presented at 33 workshops in various areas of computational sciences, ranging from computational science technologies to specific areas of computational sciences, such as software engineering, security, artificial intelligence and blockchain technologies.

Radiotherapy treatment planning optimization employs metrics for the quantification of plan quality indicators based on a set of input desired criteria by the planner. Patient-specificity in current practice is limited to the customization and refinement of input optimization criteria to contextualize relative urgency. The arc geometry and machine trajectory in radiotherapy planning can create additional opportunities for optimization on a patient-specific basis. This work proposes novel technologies capable of leveraging new degrees of freedom in the domain of radiotherapy to improve radiotherapy plan quality. A series of four manuscripts form the basis for this thesis. The first manuscript, "Overlap Guided Fixed Patient Support Positioning Optimization for Cranial SRT", is an investigation into the optimization of couch rotation angle in the standard cranial stereotactic VMAT template to reduce the presence of overlap of sensitive structures with the targeted tissues in the aperture of the radiation beam. The second manuscript, "Dynamic Collimator Trajectory Algorithm for Multiple Metastases Dynamic Conformal Arc Treatment Planning", demonstrates a novel method of reducing the presence of uncollimated non-target anatomy from the aperture of the radiation beam and increases the efficacy of collimation by optimizing the rotation angles of the multi-leaf collimator. Additionally, it proposes the use of dynamically updated collimator angle throughout delivery to maximize the capacity of this optimization. The third manuscript, "Intra-Arc Binary Collimation Algorithm for the Optimization of Stereotactic Radiotherapy Treatment of Multiple Metastases with Multiple Prescriptions", demonstrates a novel method of aperture design in multiple metastases cranial radiosurgery which maximizes the presence of conformal aperture to increase the efficiency of monitor units, while regularly shielding targets completely to modulate dose to meet target prescription and healthy tissues sparing. Finally, the fourth manuscript, "CODA: Combined Optimization of Dynamic Axes", is the first investigation into the synergistic optimization of the rotation angle of the collimator, the rotation angle of the treatment couch, and the rotation angle of the gantry to accomplish the objectives of normal tissue sparing and treatment efficiency using a novel organization of cost function and trajectory design. These manuscripts form the basis for automated optimization of linear accelerator trajectories in cranial radiosurgery. Their implementation can result in significant increases in plan quality when compared to state of the art conventional treatment planning. The introduction of these additional forms of optimization can be used to mitigate the effects of inter-planner variation in plan quality by automating the steps performed in expert-planning.

"The Varian TrueBeam STx linear accelerator features a developer's mode in which treatment plans can be programmed that include patient couch motion during radiation delivery. The combination of synchronous couch/gantry trajectories with Varian volumetric modulated arc therapy (VMAT) optimizations, called RapidArc, can result in a treatment technique that has been designated Virtual Isocenter RapidArc (VIRA). Prior to its implementation, the accuracy of dose calculations in the Varian Eclipse treatment planning system, on which the RapidArc optimization depends, must be validated, as well as the positional accuracy of the TrueBeam patient couch. The dose calculation accuracy was evaluated extrinsically through the delivery of clinical dynamic multileaf collimator (DMLC) intensity modulated radiotherapy (IMRT) treatment plans as a function of source-to-surface distance (SSD) and measurement with ionization chamber and Gafchromic EBT3 film. Parameters intrinsic to dose calculations in Eclipse, the dosimetric leaf gap (DLG) and leaf transmission (LT), were also investigated for their dependence on SSD. The positional accuracy of the treatment couch was assessed through the generation of treatment plans with static couch/gantry, static couch/rotating gantry, and synchronous couch and gantry motion, with measurement of the real-time ionization chamber current positioned in a cylindrical phantom during radiation delivery. The relative agreement of ionization chamber measurements to Eclipse dose calculations for DMLC IMRT treatment plans decreased by 1.5±0.3% over SSDs in the range of 85 cm to 135 cm (less than 1.0% deviation from standard clinical reference conditions of 100 cm SSD). Gafchromic EBT3 film measurements were consistent with ionization chamber results, though noise in the film data at low doses resulted in large uncertainties. Measurements of DLG were independent of SSD, following corrections for geometric projection. LT showed a dependence on SSD of 0.09±0.02% over the SSD range investigated. The ionization chamber current measurements for synchronous couch and gantry rotation, analogous to the proposed VIRA technique, indicated a maximum deviation of 0.2 cm relative to treatment isocenter, equal to the deviation observed for the rotating gantry/static couch treatment, analogous to conventional VMAT delivery. These results indicate that the Varian TrueBeam and Eclipse maintain the necessary positional and dosimetric accuracy required for VMAT treatments involving dynamic couch trajectories." --

External-beam radiotherapy has long been challenged by the simple fact that patients can (and do) move during the delivery of radiation. Recent advances in imaging and beam delivery technologies have made the solution-adapting delivery to natural movement-a practical reality. Adaptive Motion Compensation in Radiotherapy provides the first detailed

Stereotactic radiosurgery is a high-dose therapeutic technique for treating cranial lesions. To ensure that treatment is safe and effective several techniques are employed, namely: (1) Image guidance to ensure accurate patient positioning (e.g. pre-treatment cone-beam computed tomography); (2) Use of immobilization devices (e.g. invasive frames or non-invasive thermoplastic masks) that fixate the patient to the treatment couch during therapy. Despite these efforts, intra-fraction motion on the order of several millimetres or degrees can occur that could impact target coverage, and dose received to healthy tissues. This work aims to quantify the dosimetric impact of motion during radiosurgery and develop two methodologies for addressing motion: 1) megavoltage (MV) imaging with region of interest (ROI) apertures to detect and correct for motion with couch translations. 2) Dynamic couch trajectories to minimize treatment distances during delivery which could improve treatment efficiency, potentially minimizing the magnitude and/or frequency of motion.