In vivo verification of radiation dose to healthy tissue during radiotherapy for breast cancer

Cancer is one of the most prevalent diseases affecting the developed world. Breast cancer is a particularly common form of this disease affecting women with an estimated 1 in 8 expected to receive a diagnosis in her lifetime. Radiation therapy (radiotherapy) involves targeting cancerous cells with a high dose of ionising radiation, administered either externally (external beam radiotherapy) or via interstitial radioactive sources (brachytherapy) and may be offered as a treatment option in addition to surgery, chemotherapy, immunotherapy, or as a standalone treatment. Despite its efficacy, radiotherapy carries some risk of damaging healthy cells as well as the targeted cancerous cells which it aims to destroy. In order to deliver the therapeutic radiation doses required for tumour control, a relatively small yet still potentially harmful dose of radiation is inevitably received by surrounding healthy tissue located beyond the targeted region. This radiation dose, termed ‘out-of-field’ dose, arises from leakage radiation and scatter events within the medical linear accelerator, scatter from treatment accessories, and from within the patient. Modern management strategies as well as trends towards earlier diagnosis have translated to longer survival rates for breast cancer patients. The unfortunate corollary is twofold; one, that treatment side effects have longer to manifest, and two, patients may live longer with any treatment side effects which do present. As a result, increased emphasis is being turned to potential side effects of radiation treatment. With 5-year survival rates close to 90% for early stage breast cancer, it is no longer appropriate to ignore potential long-term treatment side effects such as second cancer induction. Unfortunately, out-of-field doses arising from radiotherapy treatment are not well modelled by commercial treatment planning systems. The doses received by untargeted healthy tissues therefore are often not well known, let alone optimised. This thesis addresses the increasingly pressing need to characterise the out-of-field dose received by untargeted healthy tissue during external beam radiotherapy for breast cancer. This is achieved through in vivo dosimetry whereby out-of-field doses are measured directly on patients as they undergo radiotherapy treatment. Specialised thermoluminescent dosimeters (TLDs) sensitive to low radiation doses were used, since most commercial detectors lack the sensitivity, dose linearity, and relatively flat energy response that is required for accurate dosimetry at out-of-field locations where the radiation environment is not precisely known. In vivo measurements were compared to doses calculated from a commercial treatment planning system (TPS) in order to assess the extent to which dose calculated from a commercial planning system differed from measurements. In order to further explore individual effects of various treatment parameters, such as the choice of beam energy and treatment field size, a series of controlled measurements were performed in a 2 phantom. A customised detector was designed to facilitate direct measurements of leakage radiation at the patient plane under various radiotherapy conditions. A correction for leakage radiation was derived as a result of phantom and in vivo measurements, providing improved dose estimates at outof-field locations. Skin reactions are a common side effect of breast radiotherapy and skin dose estimates from commercial treatment planning systems are often inaccurate. As part of this work, a thin window (‘Markus-type’) ionisation chamber was used to systematically characterise surface dose both in- and out-of-field. With modern flattening filter free (FFF) beams fast becoming standard on most new linear accelerators, it was imperative to characterise the resulting surface dose from FFF as well as standard beams which are commonly used to deliver breast radiotherapy in many centres around the world. A comparison is presented between surface dose from standard as well as modern FFF beams both inand out-of-field for a typical breast radiotherapy beam geometry. This study demonstrated that FFF beams have the potential to reduce the out-of-field dose reaching areas of skin during radiotherapy for breast cancer. As this work shows, consequences for surface dose within the radiotherapy field depended largely on choice of beam energy and field size. This thesis provides a comprehensive assessment of the out-of-field dose delivered to untargeted healthy tissues during radiotherapy for breast cancer. Various dosimetry techniques were applied, requiring specialised TLD materials, thin window ionisation chamber measurements, dose calculations from various algorithms within a commercial treatment planning system, and the design and implementation of a novel collimated detector system to isolate the leakage component of out-of-field dose. Technological as well as patient-specific factors were explored; in vivo dosimetry is applied not only to standard breast radiotherapy but also expanded to include state-of-the-art stereotactic ablative body radiotherapy, where higher doses per fraction are delivered, to further assess leakage radiation in vivo at locations further from the treatment region than would be possible during conventional fractionation regimens. FFF beams were studied in detail to provide insight into potential implications of modern radiotherapy technologies. The findings from this work will help to better understand the risks associated with radiotherapy for breast cancer, and encourage the use of simple strategies to help minimise these risks, thus translating to more favourable outcomes for the large number of patients undergoing radiotherapy every year

Assessment of leakage dose in vivo in patients undergoing radiotherapy for breast cancer

Background and purpose Accurate quantification of the relatively small radiation doses delivered to untargeted regions during breast irradiation in patients with breast cancer is of increasing clinical interest for the purpose of estimating long-term radiation-related risks. Out-of-field dose calculations from commercial planning systems however may be inaccurate which can impact estimates for long-term risks associated with treatment. This work compares calculated and measured dose out-of-field and explores the application of a correction for leakage radiation. Materials and methods Dose calculations of a Boltzmann transport equation solver, pencil beam-type, and superposition-type algorithms from a commercial treatment planning system (TPS) were compared with in vivo thermoluminescent dosimetry (TLD) measurements conducted out-of-field on the contralateral chest at points corresponding to the thyroid, axilla and contralateral breast of eleven patients undergoing tangential beam radiotherapy for breast cancer. Results Overall, the TPS was found to under-estimate doses at points distal to the radiation field edge with a modern linear Boltzmann transport equation solver providing the best estimates. Application of an additive correction for leakage (0.04% of central axis dose) improved correlation between the measured and calculated doses at points greater than 15 cm from the field edge. Conclusions Application of a correction for leakage doses within peripheral regions is feasible and could improve accuracy of TPS in estimating out-of-field doses in breast radiotherapy

Focus! Modeling Attentional Decay Over Time Through A Vigilant Attention Paradigm

This thesis is an exploration of the time course of attentional decay using a task-related visual paradigm. Limits of attention have been observed at shorter timescales of 1-3 seconds (Gottsdanker, 1984) and longer timescales of up to an hour (Fisk and Schneider,1981). However, how attention varies as a function of task expectations is not well understood. As a part of this thesis, I conducted a study to test how the allocation of task-related attention varies as spatial and short-term temporal aspects of the task are manipulated. Participants (n=27) viewed two adjacent cartoon star stimuli and were directed to press a button when a transparency change occurred at a valid-cued or invalid-cued star. The opacity change occurred at a random time within one of four-time intervals from 1 second to 10 seconds. My analysis sought to investigate the differences in performance, quantified by reaction time, between the valid and invalid cues across the different time blocks. Additionally, I investigated whether a linear or nonlinear model could better fit the data using ML techniques, which may be indicative of nonlinear attentional decay over time. Through linear regression analysis, several effects were observed. I observed an effect of spatial cueing, such that performance was better for the valid stimuli location for all time blocks. This effect remained constant throughout each of the time blocks. Temporal attention effects included a general effect of vigilance, as across valid and invalid trials in each time block, reaction time decreased when the stimulus change occurred later in the trial. This effect of vigilance was most substantial for shorter time intervals. The differing slopes (effect) suggest that the subjects may be allocating attention throughout the paradigm. Supplementary analysis using machine learning techniques tested whether attention decay functioned in a linear or nonlinear manner, finding linear models to best represent attentional decay over time. Future research should explore whether this effect of vigilance on attention allocation is mediated as a conscious decision by the participant, as well as how allocation differs in those suffering from neurodevelopmental disorders, such as ADHD