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Purpose: To develop a novel decision-support system for radiation oncology that incorporates clinical, treatment and outcome data, as well as outcome models from a large clinical trial on magnetic resonance image-guided adaptive brachytherapy (MR-IGABT) for locally advanced cervical cancer (LACC). Methods: A system, called EviGUIDE, was developed that combines dosimetric information from the treatment planning system, patient and treatment characteristics, and established tumor control probability (TCP), and normal tissue complication probability (NTCP) models, to predict clinical outcome of radiotherapy treatment of LACC. Six Cox Proportional Hazards models based on data from 1341 patients of the EMBRACE-I study have been integrated. One TCP model for local tumor control, and five NTCP models for OAR morbidities. Results: EviGUIDE incorporates TCP-NTCP graphs to help users visualize the clinical impact of different treatment plans and provides feedback on achievable doses based on a large reference population. It enables holistic assessment of the interplay between multiple clinical endpoints and tumour and treatment variables. Retrospective analysis of 45 patients treated with MR-IGABT showed that there exists a sub-cohort of patients (20%) with increased risk factors, that could greatly benefit from the quantitative and visual feedback. Conclusion: A novel digital concept was developed that can enhance clinical decision- making and facilitate personalized treatment. It serves as a proof of concept for a new generation of decision support systems in radiation oncology, which incorporate outcome models and high-quality reference data, and aids the dissemination of evidence-based knowledge about optimal treatment and serve as a blueprint for other sites in radiation oncology.

Purpose: To develop and implement a software that enables centers, treating patients with state-of-the-art radiation oncology, to compare their patient, treatment, and outcome data to a reference cohort, and to assess the quality of their treatment approach. Materials and Methods: A comprehensive data dashboard was designed, which al- lowed holistic assessment of institutional treatment approaches. The software was tested in the ongoing EMBRACE-II study for locally advanced cervical cancer. The tool created individualized dashboards and automatic analysis scripts, verified pro- tocol compliance and checked data for inconsistencies. Identified quality assurance (QA) events were analysed. A survey among users was conducted to assess usability. Results: The survey indicated favourable feedback to the prototype and highlighted its value for internal monitoring. Overall, 2302 QA events were identified (0.4% of all collected data). 54% were due to missing or incomplete data, and 46% originated from other causes. At least one QA event was found in 519/1001 (52%) of patients. QA events related to primary study endpoints were found in 16% of patients. Sta- tistical methods demonstrated good performance in detecting anomalies, with precisions ranging from 71% to 100%. Most frequent QA event categories were Treatment Technique (27%), Patient Characteristics (22%), Dose Reporting (17%), Outcome 156 (15%), Outliers (12%), and RT Structures (8%). Conclusion: A software tool was developed and tested within a clinical trial in radia- tion oncology. It enabled the quantitative and qualitative comparison of institutional patient and treatment parameters with a large multi-center reference cohort. We demonstrated the value of using statistical methods to automatically detect implau- sible data points and highlighted common pitfalls and uncertainties in radiotherapy for cervical cancer.

Background and purpose: Image-guided adaptive brachytherapy (IGABT) is an important modality in the cervical cancer treatment, and plan quality is sensitive to time pressure in the workflow. Patient anatomy-based quality-assurance (QA) with overlap volume histograms (OVHs) has been demonstrated to detect suboptimal plans (outliers). This analysis quantifies the possible improvement of plans detected as outliers, and investigates its suitability as a clinical QA tool in a multi-center setting. Materials and methods: In previous work OVH-based models were investigated for the use of QA. In this work a total of 160 plans of 68 patients treated in accordance with the current state-of-the-art IGABT protocol from Erasmus MC (EMC) were analyzed, with a model based on 120 plans (60 patients) from UMC Utrecht (UMCU). Machine-learning models were trained to define QA thresholds, and to predict dose D2cm3 to bladder, rectum, sigmoid and small bowel with the help of OVHs of the EMC cohort. Plans out of set thresholds (outliers) were investigated and retrospectively replanned based on predicted D2cm3 values. Results: Analysis of replanned plans demonstrated a median improvement of 0.62 Gy for all Organs At Risk (OARs) combined and an improvement for 96 % of all replanned plans. Outlier status was resolved for 36 % of the replanned plans. The majority of the plans that could not be replanned were reported having implantation complications or insufficient coverage due to tumor geometry. Conclusion: OVH-based QA models can detect suboptimal plans, including both unproblematic BT applications and suboptimal planning circumstances in general. OVH-based QA models demonstrate potential for clinical use in terms of performance and user-friendliness, and could be used for knowledge transfer between institutes. Further research is necessary to differentiate between (sub)optimal planning circumstances.

Background and purpose: Image-guided adaptive brachytherapy (IGABT) is a key component in the treatment of cervical cancer, but the nature of the clinical workflow makes it vulnerable to suboptimal plans, as the theoretical optimal plan depends heavily on organ configuration. Patient anatomy-based quality-assurance (QA) with overlap volume histograms (OVHs) is a promising tool to detect such suboptimal plans, and in this analysis its suitability as a multi-institutional clinical QA tool is investigated. Materials and methods: A total of 223 plans of 145 patients treated in accordance with the current state-of-the-art IGABT protocols from UMC Utrecht (UMCU) and Erasmus MC (EMC) were included. Machine-learning models were trained to predict dose D2cm3 to bladder, rectum, sigmoid and small bowel with the help of OVHs. For this strategy, points are sampled on the organs-at-risk (OARs), and the distances of the sampled points to the target are computed and combined in a histogram. Machine-learning models can then be trained to predict dose-volume histograms (DVHs) for unseen data. Single-center model robustness to needle use and applicator type and multi-center model translatability were investigated. Performance of models was assessed by the difference between planned (clinical) and predicted D2cm3 values. Results: Intra-validation of UMCU data demonstrated OVH model robustness to needle use and applicator type. The model trained on UMCU data was found to be robust within the same protocol on EMC data, for all investigated OARs. Mean squared error between planned and predicted D2cm3 values of OARs ranged between 0.13 and 0.40 Gy within the same protocol, indicating model translatability. For the former protocol cohort of Erasmus MC large deviations were found between the planned and predicted D2cm3 values, indicating plan deviation from protocol. Mean squared error for this cohort ranged from 0.84 to 4.71 Gy. Conclusion: OV

The publication of the GEC-ESTRO recommendations one decade ago was a significant step forward for reaching international consensus on adaptive target definition and dose reporting in image guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. Since then, IGABT has been spreading, particularly in Europe, North America and Asia, and the guidelines have proved their broad acceptance and applicability in clinical practice. However, a unified approach to volume contouring and reporting does not imply a unified administration of treatment, and currently both external beam radiotherapy (EBRT) and IGABT are delivered using a large variety of techniques and prescription/fractionation schedules. With IGABT, local control is excellent in limited and well-responding tumours. The major challenges are currently loco-regional control in advanced tumours, treatment-related morbidity, and distant metastatic disease. Emerging evidence from the RetroEMBRACE and EMBRACE I studies has demonstrated that clinical outcome is related to dose prescription and technique. The next logical step is to demonstrate excellent clinical outcome with the most advanced EBRT and brachytherapy techniques based on an evidence-based prospective dose and volume prescription protocol. The EMBRACE II study is an interventional and observational multicentre study which aims to benchmark a high level of local, nodal and systemic control while limiting morbidity, using state of the art treatment including an advanced target volume selection and contouring protocol for EBRT and brachytherapy, a multi-parametric brachytherapy dose prescription protocol (clinical validation of dose constraints), and use of advanced EBRT (IMRT and IGRT) and brachytherapy (IC/IS) techniques (clinical validation). The study also incorporates translational research including imaging and tissue biomarkers.

Developing a more thorough understanding of what motivates young people to adopt sustainable behaviours is an important area of concern that has practical implications for creating sound educational interventions and ensuring a sustainable future. The overall purpose of this thesis was to assess and understand primary- and high-school students’ environmentally sustainable behaviours in order to inform educational interventions. Moreover, it aimed at analysing one particular socially sustainable behavioural intention among university students, notably their intention to buy fair trade products. The theory of planned behaviour (TPB) was used as the basic theoretical framework to examine these behaviours. We first conducted a pilot study for each behaviour, with the aim to identify salient beliefs of the target populations with regard to the behaviour investigated. Open-ended questionnaires were administered to a sample of 116 primary-school students, 92 high-school students, and 17 voluntary participants at the university level. A content analysis of the participants’ responses allowed the determination of the most salient beliefs, which were used as the basis for the quantitative measures of beliefs in the main studies. The first and second main studies investigated the beliefs of 812 primary-school students and 602 high-school students regarding the adoption of pro-environmental behaviours using a longitudinal approach. The gist of our results seems to be that for both age groups, educational interventions should target control beliefs especially. For instance, students insist on tools that would facilitate pro-environmental behaviours (e.g., having duplex printers or recycling bins at school and at home). However, behavioural and normative beliefs should not be neglected. The last study examined mainly differences in male and female university students’ intentions to consume fair trade products. The results indicate that for women, more emphasis should be placed on

Developing a more thorough understanding of what motivates young people to adopt sustainable behaviours is an important area of concern that has practical implications for creating sound educational interventions and ensuring a sustainable future. The overall purpose of this thesis was to assess and understand primary- and high-school students’ environmentally sustainable behaviours in order to inform educational interventions. Moreover, it aimed at analysing one particular socially sustainable behavioural intention among university students, notably their intention to buy fair trade products. The theory of planned behaviour (TPB) was used as the basic theoretical framework to examine these behaviours. We first conducted a pilot study for each behaviour, with the aim to identify salient beliefs of the target populations with regard to the behaviour investigated. Open-ended questionnaires were administered to a sample of 116 primary-school students, 92 high-school students, and 17 voluntary participants at the university level. A content analysis of the participants’ responses allowed the determination of the most salient beliefs, which were used as the basis for the quantitative measures of beliefs in the main studies. The first and second main studies investigated the beliefs of 812 primary-school students and 602 high-school students regarding the adoption of pro-environmental behaviours using a longitudinal approach. The gist of our results seems to be that for both age groups, educational interventions should target control beliefs especially. For instance, students insist on tools that would facilitate pro-environmental behaviours (e.g., having duplex printers or recycling bins at school and at home). However, behavioural and normative beliefs should not be neglected. The last study examined mainly differences in male and female university students’ intentions to consume fair trade products. The results indicate that for women, more emphasis should be placed on

The current study examined to what extent attitude, social norm, and perceived behavioral control explain students’ intentions to buy fair-trade products. Moreover, it was explored whether the addition of moral norm to these three factors permitted the better prediction of the intentions in question. Questionnaire data was collected from 192 students of the University of Luxemburg. The results of structural equation analyses revealed that attitude and perceived behavioral control explained 61% of the variance in intention. The addition of the moral norm construct increased the explained variance of intention from 61% to 73%. These results suggest that to encourage students to buy fair-trade products, applied social psychologists or educational institutions should create programs that develop their perceived control over the behavior, for instance, by offering the products in their canteens as well as in their food and drink dispensers. In addition, they should insist on the advantages of fair-trade consumerism to favor the development of a positive attitude. Finally, they should emphasize the moral correctness of the behavior.

The current study examined to what extent attitude, social norm, and perceived behavioral control explain students’ intentions to buy fair-trade products. Moreover, it was explored whether the addition of moral norm to these three factors permitted the better prediction of the intentions in question. Questionnaire data was collected from 192 students of the University of Luxemburg. The results of structural equation analyses revealed that attitude and perceived behavioral control explained 61% of the variance in intention. The addition of the moral norm construct increased the explained variance of intention from 61% to 73%. These results suggest that to encourage students to buy fair-trade products, applied social psychologists or educational institutions should create programs that develop their perceived control over the behavior, for instance, by offering the products in their canteens as well as in their food and drink dispensers. In addition, they should insist on the advantages of fair-trade consumerism to favor the development of a positive attitude. Finally, they should emphasize the moral correctness of the behavior.

The current study examined to what extent attitude, social norm, and perceived behavioral control explain students’ intentions to buy fair-trade products. Moreover, it was explored whether the addition of moral norm to these three factors permitted the better prediction of the intentions in question. Questionnaire data was collected from 192 students of the University of Luxemburg. The results of structural equation analyses revealed that attitude and perceived behavioral control explained 61% of the variance in intention. The addition of the moral norm construct increased the explained variance of intention from 61% to 73%. These results suggest that to encourage students to buy fair-trade products, applied social psychologists or educational institutions should create programs that develop their perceived control over the behavior, for instance, by offering the products in their canteens as well as in their food and drink dispensers. In addition, they should insist on the advantages of fair-trade consumerism to favor the development of a positive attitude. Finally, they should emphasize the moral correctness of the behavior.