Safety culture to improve accidental events reporting in radiotherapy

The potential for unintended and adverse radiation exposure in radiotherapy is real and should be studied because radiotherapy is a highly complex, multistep process which requires input from numerous individuals from different areas and steps of the radiotherapy workflow. The 'Incident' (I) is a consequence of which are not negligible from the point of view of protection or safety. A 'near miss' (NM) is defined as an event which is highly likely to happen but did not occur. The purpose of this work is to show that through a systematic reporting and analysis of these adverse events, their occurrence can be reduced

Optimization strategies for respiratory motion management in stereotactic body radiation therapy

Various challenges arise during the treatment of lung tumors with stereotactic body radiation therapy (SBRT), which is a form of hypofractionated high precision conformal radiation therapy delivered to small targets. The dose is applied in only a few fractions and respiratory organ and tumor motion is a source of uncertainty additional to interfractional set-up errors. Respiratory organ and tumor motion is highly patient-specific and it affects the whole radiotherapy treatment chain. In this thesis, motion management techniques for SBRT are evaluated and improved in a clinical setting. A clinical need for improvement has been present at the LMU university hospital for each issue addressed in this thesis: Initially, the usage of respiratory correlated computed tomography (4DCT), which is vital for SBRT treatment, was seen as impractical and prone to uncertainties in the data reconstruction in its current form. Therefore, the 4DCT reconstruction workflow has been improved to minimize these potential error sources. Secondly, treatment planning for tumors affected by respiratory motion was evaluated and subsequently improved. Finally, the treatment technique of respiratory gating was implemented at the clinic, which led to the need of evaluating the respiratory gating characteristics of the novel system configuration. At first, the 4DCT reconstruction workflow used in clinical practice was investigated, as in the presence of respiratory motion the knowledge of tumor position over time is essential in SBRT treatments. Using 4DCT, the full motion range of the individual tumor can be determined. However, certain 4DCT reconstruction methods can under- or overestimate tumor motion due to limitations in the data acquisition scheme and due to the incorrect sorting of certain X-ray computed tomography (CT) image slices into different respiratory phases. As the regular clinical workflow of cycle-based sorting (CBS) without maximum inspiration detection (and therefore no clear starting point for the individual breathing cycles) seemed to be affected by these potential errors, the usage of CBS with correct maximum detection and another sorting algorithm of the respiration states, so-called local amplitude-based sorting (LAS), both have been implemented for a reduction of image artifacts and improved 4DCT quality. The three phase binning algorithms have been investigated in a phantom study (using 10 different breathing waveforms) and in a patient study (with 10 different patients). The mis-representation of the tumor volume was reduced in both implemented sorting algorithms compared to the previously used CBS approach (without correct maximum detection) in the phantom and the patient study. The clinical recommendation was the use of CBS with improved maximum detection, as too many manual interventions would be needed for the LAS workflow. Secondly, a combination of the actual patient breathing trace during treatment, the log files generated by the linear accelerator (LINAC), and Monte Carlo (MC) four-dimensional (4D) dose calculations for each individual fraction was implemented as a 4D dose evaluation tool. This workflow was tested in a clinical environment for SBRT treatment planning on multiple CT datasets featuring: a native free-breathing 3DCT, an average intensity projection (AIP) as well as a maximum intensity projection (MIP), both obtained from the patient's 4DCT, and density overrides (DOs) in a 3DCT. This study has been carried out for 5 SBRT patients for three-dimensional conformal radiation therapy (3D-CRT) and volumetric modulated arc therapy (VMAT) treatment plans. The dose has been recalculated on each 4DCT breathing phase according the the patient's breathing waveform and accumulated to the gross tumor volume (GTV) at the end-of-exhale (EOE) breathing phase using deformable image registration. Even though the least differences in planned and recalculated dose were found for AIP and MIP treatment planning, the results indicate a strong dependency on individual tumor motion due to the variability of breathing motion in general, and on tumor size. The combination of the patient's individual breathing trace during each SBRT fraction with 4D MC dose calculation based on the LINAC log file information leads to a good approximation of actual dose delivery. Finally, in order to ensure precise and accurate treatment for respiratory gating techniques, the technical characteristics of the LINAC in combination with a breathing motion monitoring system as s surrogate for tumor motion have to be identified. The dose delivery accuracy and the latency of a surface imaging system in connection with a modern medical LINAC were investigated using a dynamic breathing motion phantom. The dosimetric evaluation has been carried out using a static 2D-diode array. The measurement of the dose difference between gated and ungated radiation delivery was found to be below 1% (for clinical relevant gating levels of about 30%). The beam-on latency, or time delay, determined using radiographic films was found to be up to 851 ms±100 ms. With these known parameters, an adjustment of the pre-selected gating level or the internal target volume (ITV) margins could be made. With the highly patient-specific character of respiratory motion, lung SBRT faces many additional challenges besides the specific issues addressed in this thesis. However, the findings of this thesis have improved clinical workflows at the Department of Radiation Oncology of the LMU University hospital. In a future perspective, a workflow using evaluation of the actual 4D dose in combination with accurate 4DCT image acquisition and specialized treatment delivery (such as respiratory gating) has the potential for a safe further reduction of treatment margins and increased sparing of organs-at-risk (OARs) in SBRT without compromising tumor dose targeting accuracy

Reducing Inappropriate Polypharmacy for Older Inpatients: Development of In-Hospital Interventions Based on Benzodiazepine Deprescribing

There are many barriers to deprescribing in the routine care of older inpatients with polypharmacy. Implementation is limited by factors related to medications, clinicians, patients, and the acute care setting. It is challenging to deprescribe medications such as benzodiazepines (BZDs) with complex reduction regimens due to their withdrawal symptoms, so the process must continue beyond the hospital discharge and involve community clinicians like general practitioners (GPs). However, there is clinical benefit in deprescribing these medications, because long term use of BZDs by older patients is associated with considerable harm including falls, delirium, and a significant financial and legal burden to society. Aims The overall aim of this thesis was to develop two specific interventions to improve deprescribing from hospital as part of a wider research program, developing a multi-strategic intervention. These are an e-learning module and a preferred language guide for communicating deprescribing decisions. The thesis is based on the hypotheses that 1) Providing education will increase multidisciplinary hospital clinician knowledge and self-efficacy of polypharmacy and deprescribing. 2) Identification of local barriers and degree of self-efficacy for deprescribing amongst hospital clinicians would assist in targeting interventions. 3) Co-design of a standardised template to communicate deprescribing decisions with both writers and receivers will lead to a balance of appropriate information being communicated. Literature Review This thesis uses BZD deprescribing as a model. A literature review of interventions for BZD deprescribing confirmed variable success rates across a heterogeneity of methodological approaches. These interventions were classified by target population (physician, pharmacist, or patients) and then classified against the Behaviour Change Wheel taxonomy. This review confirmed the benefit of multi-strategic interventions and appropriate dose reduction regimens to inform the rest of the study. Development of e-learning module, immediate impact on medical students and assessment of hospital clinician perceptions and practice on deprescribing Secondly, an e-learning module on deprescribing was developed in conjunction with the Health Education and Training Institute (HETI) of New South Wales Health, targeting all clinicians involved in care of older inpatients. Following completion of the module, eligible hospital clinicians completed a quantitative questionnaire to describe their perceptions and practice of deprescribing. Senior medical students also completed this questionnaire in a pre-post manner to describe the immediate impact of the module. Hospital clinicians and senior medical students reported limited self-efficacy in deprescribing, especially in developing plans and implementing them. Hospital clinicians also reported that they did not deprescribe frequently, despite a general awareness of polypharmacy. Differences were identified in clinical roles: Junior doctors do not perceive deprescribing as part of their clinical role whereas non-medication reviewing clinicians (nurses and allied health) have an interest in contributing more to deprescribing in hospital. Pre-post analysis of medical student responses found a small but statistically significant improvement in these areas after viewing the module. The module is likely to be a useful component of a multi-strategic intervention and information gained around local barriers and enablers will be used to inform the rest of the intervention. Developing a preferred language guide to effectively communicate in-hospital deprescribing decisions Finally, a preferred language guide to assist with communicating deprescribing decisions was developed using a qualitative approach. Semi-structured interviews and focus groups involving clinicians who send and receive discharge summaries informed development of the guide. As a result, a novel, structured, copy-and-paste, fill-in-the-blanks template was developed and integrated within a concurrently developed deprescribing guide. This aimed to keep the message specific and concise whilst still allowing the GP autonomy to carry out patient care. Conclusion Two specific interventions have been developed to address in-hospital barriers to deprescribing: an education module addressing knowledge and self-efficacy of polypharmacy and deprescribing, and a communication guide to improve communication of deprescribing decisions made in hospital at transitions of care. Further evaluation of the complete intervention is required, and consideration should be given to evaluation with an implementation science approach. The research findings suggest potential for future interventions that also target the admitted patient and non-medication reviewing clinicians, to improve in-hospital deprescribing and reduce medication related harm

Comprehensive quality control process for high precision intensity modulated adaptive proton therapy

The thesis focuses on development and clinical implementation of comprehensive and overlaying quality control process aimed at supporting introduction of high precision adaptive IMPT workflows. The thesis consists of seven chapters, covering topics on quality control for proton range accuracy, reconstruction, and accumulation of delivered dose distributions longitudinally throughout the proton therapy course and independent dose recalculation/predictive outcome-based patient specific quality assurance procedures. A proton range probing method as a quality control tool for range accuracy validation has been proposed and applied for range accuracy assessments in animal tissue samples covering a broad range of tissue types. A fraction-wise 4D dose reconstruction and accumulation procedure utilizing treatment delivery log files and patient-specific daily breathing patterns has been proposed and implemented in clinical practice. Validation of the procedure in controlled conditions with a 4D phantom revealed ability to spatially reconstruct the dose distributions with submillimeter accuracy. Eventually, an alternative approach for in-beam measurement-based patient specific quality assurance (PSQA) procedure has been investigated, developed, and introduced in clinical practice. By incorporating the developed range probing QC procedure as a validation tool for synthetic CTs and utilizing developed dose reconstruction and accumulation workflow, it enables possibility to establish a comprehensive longitudinal patient specific quality control process to monitor the treatment delivery in an environment of adaptive proton therapy. Introduction of more adaptive treatment procedures and availability of online adaptive workflows in proton therapy might be the next major advancement needed to take full advantage of the physical characteristics of the proton beam

Personalized treatment planning in eye brachytherapy for ocular melanoma: Dosimetric analysis on ophthalmic structure at risk

Purpose: To evaluate the impact on dose distribution to eye organs-at-risk (eOARs) of a computed tomography (CT)-based treatment planning in eye plaque brachytherapy (EPB) treatment. Methods: We analyzed 19 ocular melanoma patients treated with ruthenium-106 plaques to a total dose of 100 Gy to tumor apex using conventional central-axis-point dose calculation. Treatments were re-planned using the Plaque Simulator (PS) software implementing two different strategies: a personalized CT-eye-model (CT-PS) and a standard-eye-model (SEM-PS) defined by Collaborative Ocular Melanoma Study. Dice coefficient and Hausdorff distance evaluated the concordance between eye-bulb-models. Mean doses (Dmean) to tumor and eOARs were extracted from Dose-Volume-Histograms and Retinal-Dose-Area-Histogram. Differences between planning approaches were tested by Wilcoxon signed-rank test. Results: In the analyzed cohort, 8 patients (42%) had posterior tumor location, 8 (42%) anterior, and 3 (16%) equatorial. The SEM did not accurately described the real CT eye-bulb geometry (median Hausdorff distance 0.8 mm, range: (0.4–1.3) mm). Significant differences in fovea and macula Dmean values were found (p = 0.04) between CT-PS and SEM-PS schemes. No significant dosimetric differences were found for tumor and other eOARs. The planning scheme particularly affects the OARs closest to the tumor with a general tendency of SEM-PS to overestimate the doses to the OARs closest to the tumor. Conclusion: The dosimetric accuracy achievable with CT-PS EPB treatment planning may help to identify ocular melanoma patients who could benefit the most from a personalized eye dosimetry for an optimal outcome in terms of tumor coverage and eOARs sparing. Further research and larger studies are underway

Adaptive Radiotherapy for Lung Cancer Using Uniform Scanning Proton Beams

Lung cancer remains the leading cause of cancer death in North America and is one of the major indications for proton therapy. Proton beams provide a superior dose distribution due to their finite ranges, but where they stop in the tissue is very sensitive to anatomical change. To ensure optimal target coverage and normal tissue sparing in the presence of geometrical variations, such as tumor shrinkage and other anatomical changes, adaptive planning is necessary in proton therapy of lung cancer. The objective of the chapter is to illustrate the rationale, process, and strategies in adaptive lung cancer treatment using uniform scanning proton beams. In addition, practical considerations for adaptive proton planning are discussed, such as software limitations, the associated costs and risks, and the criteria on whether and how to adapt a plan

Integrated navigation and visualisation for skull base surgery

Skull base surgery involves the management of tumours located on the underside of the brain and the base of the skull. Skull base tumours are intricately associated with several critical neurovascular structures making surgery challenging and high risk. Vestibular schwannoma (VS) is a benign nerve sheath tumour arising from one of the vestibular nerves and is the commonest pathology encountered in skull base surgery. The goal of modern VS surgery is maximal tumour removal whilst preserving neurological function and maintaining quality of life but despite advanced neurosurgical techniques, facial nerve paralysis remains a potentially devastating complication of this surgery. This thesis describes the development and integration of various advanced navigation and visualisation techniques to increase the precision and accuracy of skull base surgery. A novel Diffusion Magnetic Resonance Imaging (dMRI) acquisition and processing protocol for imaging the facial nerve in patients with VS was developed to improve delineation of facial nerve preoperatively. An automated Artificial Intelligence (AI)-based framework was developed to segment VS from MRI scans. A user-friendly navigation system capable of integrating dMRI and tractography of the facial nerve, 3D tumour segmentation and intraoperative 3D ultrasound was developed and validated using an anatomically-realistic acoustic phantom model of a head including the skull, brain and VS. The optical properties of five types of human brain tumour (meningioma, pituitary adenoma, schwannoma, low- and high-grade glioma) and nine different types of healthy brain tissue were examined across a wavelength spectrum of 400 nm to 800 nm in order to inform the development of an Intraoperative Hypserpectral Imaging (iHSI) system. Finally, functional and technical requirements of an iHSI were established and a prototype system was developed and tested in a first-in-patient study