Multicriteria Optimization in Inverse Radiotherapy Planning

The development of intensity-modulated radiotherapy (IMRT) has greatly enhanced the possibilities of shaping the dose distribution. However, because of physical limitations, even with IMRT a certain dose to organs at risk is unavoidable, so in treatment planning often a compromise between different plan criteria has to be found. This thesis presents a new optimization concept that is dedicated to this type of problem. It is based on the fact that there is no single optimal plan, but many so-called Pareto optimal plans, which cannot be improved in one criterion without worsening another. A database with all Pareto optimal plans is generated and the decision which compromise is clinically the best is left to the planner. Because of the higher calculation complexity, the dose calculation of the existing planning system was accelerated by a factor of three through statistical sampling of the calculation matrices. To describe a plan, a vector containing the 'equivalent uniform doses' (EUDs) of each structure is used. Therefore two EUD models were analyzed, the 'max & mean' and the 'generalized mean' model. An algorithm was developed to include the 'generalized mean' model in the plan optimization. At the end of the thesis, the database containing all Pareto optimal solutions of a clinical test case with 1 target volume and 2 organs at risk was generated and visualized. The planner can see at first sight the dependencies of the different plan elements and can decide which plan is clinically the best

The importance of participation for Christian children’s spiritual education

This essay addresses the negative influence that consumerism can have on children’s development and looks in particular at how it impacts their spiritual growth. Using evidence from psychology and educational studies, it makes the case that a ‘learning-by-doing’ approach is more effective than employing a system of exchange in spiritual education (whereby the adult is cast as producer and the child as consumer). This participative approach will not only establish the children in their faith, but also strengthen the faith of the adults and the whole church community in turn. (This paper was selected as the winning entry in the 2018 Fraser Essay Prize competition.

Feasibility of automated proton therapy plan adaptation for head and neck tumors using cone beam CT images

Background: Intensity modulated proton therapy (IMPT) of head and neck (H&N) tumors may benefit from plan adaptation to correct for the dose perturbations caused by weight loss and tumor volume changes observed in these patients. As cone beam CT (CBCT) is increasingly considered in proton therapy, it may be possible to use available CBCT images following intensity correction for plan adaptation. This is the first study exploring IMPT plan adaptation on CBCT images corrected and delineated by deformable image registration of the planning CT (pCT) to the CBCT, yielding a virtual CT (vCT). Methods: A Morphons algorithm was used to deform the pCTs and corresponding delineations of 9 H&N cancer patients to a weekly CBCT acquired within +/- 3 days of a control replanning CT scan (rpCT). The IMPT treatment plans were adapted using the vCT and the adapted and original plans were recalculated on the rpCT for dose/volume parameter evaluation of the impact of adaptation. Results: On the rpCT, the adapted plans were equivalent to the original plans in terms of target volumes D-95 and V-95, but showed a significant reduction of D-2 in these volumes. OAR doses were mostly equivalent or reduced. In particular, the adapted plans did not reduce parotid gland D-mean, but the dose to the optical system. For three patients the spinal cord or brain stem received higher, though well below tolerance, maximum dose. Subsequent tightening of the treatment planning constraints for these OARs on new vCT-adapted plans did not degrade target coverage and yielded pCT equivalent plans on the vCT. Conclusions: An offline automated procedure to generate an adapted IMPT plan on CBCT images was developed and investigated. When evaluating the adapted plan on a control rpCT we observed reduced D-2 in target volumes as major improvement. OAR sparing was only partially improved by the procedure. Despite potential limitations in the accuracy of the vCT approach, an improved quality of the adapted plans could be achieved

Intensity modulated or fractionated stereotactic reirradiation in patients with recurrent nasopharyngeal cancer

<p>Abstract</p> <p>Purpose</p> <p>To report our experience with intensity-modulated or stereotactic reirradiation in patients suffering from recurrent nasopharyngeal carcinoma</p> <p>Patients and Methods</p> <p>The records of 17 patients with recurrent nasopharygeal carcinoma treated by intensity-modulated (n = 14) or stereotactic (n = 3) reirradiation in our institution were reviewed. Median age was 53 years and most patients (n = 14) were male. The majority of tumors showed undifferentiated histology (n = 14) and infiltration of intracranial structures (n = 12). Simultaneous systemic therapy was applied in 8 patients. Initial treatment covered the gross tumor volume with a median dose of 66 Gy (50-72 Gy) and the cervical nodal regions with a median dose of 56 Gy (50-60 Gy). Reirradiation was confined to the local relapse region with a median dose of 50.4 Gy (36-64Gy), resulting in a median cumulative dose of 112 Gy (91-134 Gy). The median time interval between initial and subsequent treatment was 52 months (6-132).</p> <p>Results</p> <p>The median follow up for the entire cohort was 20 months and 31 months for survivors (10-84). Five patients (29%) developed isolated local recurrences and three patients (18%) suffered from isolated nodal recurrences. The actuarial 1- and 2-year rates of local/locoregional control were 76%/59% and 69%/52%, respectively. Six patients developed distant metastasis during the follow up period. The median actuarial overall survival for the entire cohort was 23 months, transferring into 1-, 2-, and 3-year overall survival rates of 82%, 44% and 37%. Univariate subset analyses showed significantly increased overall survival and local control for patients with less advanced rT stage, retreatment doses > 50 Gy, concurrent systemic treatment and complete response. Severe late toxicity (Grad III) attributable to reirradiation occurred in five patients (29%), particularly as hearing loss, alterations of taste/smell, cranial neuropathy, trismus and xerostomia.</p> <p>Conclusion</p> <p>Reirradiation with intensity-modulated or stereotactic techniques in recurrent nasopharyngeal carcinoma is feasible and yields encouraging results in terms of local control and overall survival in patients with acceptable toxicity in patients with less advanced recurrences. However, the achievable outcome is limited in patients with involvement of intracranial structures, emphasising the need for close monitoring after primary therapy.</p

A Hierachical Evolutionary Algorithm for Multiobjective Optimization in IMRT

Purpose: Current inverse planning methods for IMRT are limited because they are not designed to explore the trade-offs between the competing objectives between the tumor and normal tissues. Our goal was to develop an efficient multiobjective optimization algorithm that was flexible enough to handle any form of objective function and that resulted in a set of Pareto optimal plans. Methods: We developed a hierarchical evolutionary multiobjective algorithm designed to quickly generate a diverse Pareto optimal set of IMRT plans that meet all clinical constraints and reflect the trade-offs in the plans. The top level of the hierarchical algorithm is a multiobjective evolutionary algorithm (MOEA). The genes of the individuals generated in the MOEA are the parameters that define the penalty function minimized during an accelerated deterministic IMRT optimization that represents the bottom level of the hierarchy. The MOEA incorporates clinical criteria to restrict the search space through protocol objectives and then uses Pareto optimality among the fitness objectives to select individuals. Results: Acceleration techniques implemented on both levels of the hierarchical algorithm resulted in short, practical runtimes for optimizations. The MOEA improvements were evaluated for example prostate cases with one target and two OARs. The modified MOEA dominated 11.3% of plans using a standard genetic algorithm package. By implementing domination advantage and protocol objectives, small diverse populations of clinically acceptable plans that were only dominated 0.2% by the Pareto front could be generated in a fraction of an hour. Conclusions: Our MOEA produces a diverse Pareto optimal set of plans that meet all dosimetric protocol criteria in a feasible amount of time. It optimizes not only beamlet intensities but also objective function parameters on a patient-specific basis

Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy

Introduction: We investigated the clinical outcome and the toxicity of trimodal therapy of malignant pleural mesothelioma (MPM) treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiotherapy (IMRT). Methods: Chemotherapy regimens included Cisplatin/Pemetrexed, Carboplatin/Pemetrexed and Cisplatin/Gemcitabine, followed by EPP. 62 patients completed the adjuvant radiotherapy. IMRT was carried out in two techniques, either step&shoot or helical tomotherapy. Median target dose was 48 Gy to 54 Gy. Toxicity was scored with the Common Terminology Criteria (CTC) for Adverse Events. We used Kaplan-Meier method to estimate actuarial rate of locoregional control (LRC),distant control (DC) and overall survival (OS),measured from the date of surgery. Rates were compared using the logrank test. For multivariate analysis the Cox proportional hazard model was used. Results: The median OS, LRC and DC times were 20.4, 31.4 and 21.4 months. The 1-,2-,3-year OS rates were 63, 42, 28 %,the LRC rates were 81, 60, 40 %,and the DC rates were 62, 48, 41 %. We observed no CTC grade 4 or grade 5 toxicity. Step&shoot and helical tomotherapy were equivalent both in dosimetric characteristics and clinical outcome. Biphasic tumor histology was associated with worse clinical outcome compared to epitheloid histology. Conclusions: Mature clinical results of trimodal treatment for MPM were presented. They indicate that hemithoracic radiotherapy after EPP can be safely administered by either step&shoot IMRT and tomotherapy. However, the optimal prospective patient selection for this aggressive trimodal therapy approach remains unclear. This study can serve as a benchmark for current and future therapy concepts for MPM