A pilot study on geometrical uncertainties for intra ocular cancers in radiotherapy.

A system for stabilising and monitoring eye movements for linac-based stereotactic radiotherapy associated with the mobile eye, the Eye Tracker, was developed. Whilst the Eye Tracker design is based on a previously reported system, the purpose of this study was to confirm that the modified version can be used with clinically acceptable treatment margins. We report the estimates of the margin required to account for inter- and intra-fraction eye motion based on data from 12 consecutive patients treated with the Eye Tracker system in place. Patients were immobilised in a head and neck mask and were required to fixate on a light source. A camera system monitored eye movements relative to CT simulation baseline measurements. The Exactrac system (Brainlab, Feldkirchen, Germany) combined with the Varian TrueBeamSTx (Varian Medical Systems, Palo Alto, CA) confirmed pre- and intra-treatment setup of the head position. Displacement/rotation of the image of the pupil/iris was determined in the lateral and superior-inferior directions using a video display. A standard margin equation was applied to estimate the margin required to account for inter- and intra-fraction eye movement. The average displacement in both directions was 0.1-0.2 mm (0.36 mm SD). All patients maintained a position within 1 mm of the intended position during treatment. Based on a Bayesian estimation of the systematic and treatment errors, accounting for displacements in two-planes and a standard deviation of the penumbral width of 1.3 mm, the estimated margins to achieve coverage of the GTV with the 95% isodose in 90% of patients was found to be less than 1 mm. Small random and systematic uncertainties due to inter- and intra-fraction movement of the eye were achieved with the Eye Tracker. Whilst the estimated margins are small (<1 mm) they need to be considered in addition to contouring and treatment delivery uncertainties.

Australasian brachytherapy audit: results of the 'end-to-end' dosimetry pilot study.

INTRODUCTION: We present the results of a pilot study to test the feasibility of a brachytherapy dosimetry audit. METHODS: The feasibility study was conducted at seven sites from four Australian states in both public and private centres. A purpose-built cylindrical water phantom was imaged using the local imaging protocol and a treatment plan was generated to deliver 1 Gy to the central (1 of 3) thermoluminescent dosimeter (TLD) from six dwell positions. RESULTS: All centres completed the audit, consisting of three consecutive irradiations, within a 2-h time period, with the exception of one centre that uses a pulsed dose rate brachytherapy unit. All TLD results were within 4.5% of the predicted value, with the exception of one subset where the dwell position step size was incorrectly applied. CONCLUSIONS: While the limited data collected in the study demonstrated considerable heterogeneity in clinical practice, the study proved a brachytherapy dosimetry audit to be feasible. Future studies should include verification of source strength using a Standard Dosimetry Laboratory calibrated chamber, a phantom that more closely mimics the clinical situation, a more comprehensive review of safety and quality assurance (QA) procedures including source dwell time and position accuracy, and a review of patient treatment QA procedures such as applicator position verification.

Encouraging lifestyle behaviour change in mild cognitive impairment patients: development of appropriate educational material.

OBJECTIVES: A healthy lifestyle may help maintain cognitive function and reduce the risk of developing dementia. This study employed a focus group approach in order to gain insight into opinions of mild cognitive impairment (MCI) patients, caregivers (CG) and health professionals (HP) regarding lifestyle and its relationship with cognition. The qualitative data were used to design, develop and pilot test educational material (EM) to help encourage lifestyle behaviour change. METHOD: Data gathering phase: structured interviews were conducted with HP (n = 10), and focus groups with MCI patients (n = 24) and CG (n = 12). EM was developed and pilot tested with a new group of MCI patients (n = 21) and CG (n = 6). RESULTS: HP alluded to the lack of clinical trial evidence for a lifestyle and MCI risk link. Although they felt that lifestyle modifications should be recommended to MCI patients, they appeared hesitant in communicating this information and discussions were often patient-driven. MCI patients lacked awareness of the lifestyle cognition link. Participants preferred EM to be concise, eye-catching and in written format, with personal delivery of information favoured. Most pilot testers approved of the EM but were heterogeneous in terms of lifestyle, willingness to change and support needed to change. CONCLUSION: MCI patients need to be made more aware of the importance of lifestyle for cognition. EM such as those developed here, which are specifically tailored for this population would be valuable for HP who, currently, appear reticent in initiating lifestyle-related discussions. Following further evaluation, the EM could be used in health promotion activities targeting MCI patients.

Lack of backscatter factor measurements in HDR applications with MOSkins.

Measurements of backscatter correction factors for intra operative (IOBT) HDR brachytherapy applicators were made using Centre for Medical Radiation Physics (CMRP), MOSFET devices. In clinical use there is an absence of backscatter material above the IOBT applicator, leading to a lower dose than predicted by conventional TG-43 dose calculations. To estimate the uncertainty in the MOSFET measurements, the dosimetric characteristics, including reproducibility, stability, linearity, and angular and energy response were measured using a HDR Ir-192 source, kilovoltage treatment unit and a high energy linac. Measurements were compared with previously published Monte Carlo data. Variability of the response of the MOSFETs due to angular variation contributed the largest uncertainty in dose measurements. Using the IOBT applicator without adequate scatter material resulted in a reduction of delivered dose of on average 10%, but was dependent on the location on the applicator and the treatment field size. Theoretical calculations based on previously published study indicated an expected reduced dose of on average 4%. MOSFET devices provide an ideal measurement tool in the presence of high dose gradients, however, the dosimetric characteristics of the detector must be accounted for when estimating the uncertainty.

A novel reciprocal and biphasic relationship between membrane cholesterol and beta-secretase activity in SH-SY5Y cells and in human platelets.

Research into the cause of Alzheimer's disease (AD) has identified strong connections to cholesterol. Cholesterol and cholesterol esters can modulate amyloid precursor protein (APP) processing, thus altering production of the Abeta peptides that deposit in cortical amyloid plaques. Processing depends on the encounter between APP and cellular secretases, and is thus subject to the influence of cholesterol-dependent factors including protein trafficking, and distribution between membrane subdomains. We have directly investigated endogenous membrane beta-secretase activity in the presence of a range of membrane cholesterol levels in SH-SY5Y human neuroblastoma cells and human platelets. Membrane cholesterol significantly influenced membrane beta-secretase activity in a biphasic manner, with positive correlations at higher membrane cholesterol levels, and negative correlations at lower membrane cholesterol levels. Platelets from individuals with AD or mild cognitive impairment (n = 172) were significantly more likely to lie within the negative correlation zone than control platelets (n = 171). Pharmacological inhibition of SH-SY5Y beta-secretase activity resulted in increased membrane cholesterol levels. Our findings are consistent with the existence of a homeostatic feedback loop between membrane cholesterol level and membrane beta-secretase activity, and suggest that this regulatory mechanism is disrupted in platelets from individuals with cognitive impairment.