Association between ambient ultraviolet radiation and risk of esophageal cancer

OBJECTIVES: Ecological studies have suggested an inverse relationship between latitude and risks of some cancers. However, associations between solar ultraviolet radiation (UVR) exposure and esophageal cancer risk have not been fully explored. We therefore investigated the association between nevi, freckles, and measures of ambient UVR over the life-course with risks of esophageal cancers. METHODS: We compared estimated lifetime residential ambient UVR among Australian patients with esophageal cancer (330 esophageal adenocarcinoma (EAC), 386 esophago-gastric junction adenocarcinoma (EGJAC), and 279 esophageal squamous cell carcinoma (ESCC)), and 1471 population controls. We asked people where they had lived at different periods of their life, and assigned ambient UVR to each location based on measurements from NASA's Total Ozone Mapping Spectrometer database. Freckling and nevus burden were self-reported. We used multivariable logistic regression models to estimate the magnitude of associations between phenotype, ambient UVR, and esophageal cancer risk. RESULTS: Compared with population controls, patients with EAC and EGJAC were less likely to have high levels of estimated cumulative lifetime ambient UVR (EAC odds ratio (OR) 0.59, 95% confidence interval (CI) 0.35-0.99, EGJAC OR 0.55, 0.34-0.90). We found no association between UVR and risk of ESCC (OR 0.91, 0.51-1.64). The associations were independent of age, sex, body mass index, education, state of recruitment, frequency of reflux, smoking status, alcohol consumption, and H. pylori serostatus. Cases with EAC were also significantly less likely to report high levels of nevi than controls. CONCLUSIONS: These data show an inverse association between ambient solar UVR at residential locations and risk of EAC and EGJAC, but not ESCC.

Adaptive radiotherapy for virally mediated head and neck cancer : predicting which patients may benefit most

Background: Recent clinical studies have demonstrated an emerging subgroup of head and neck cancers that are virally mediated. This disease appears to be a distinct clinical entity with patients presenting younger and with more advanced nodal disease, having lower tobacco and alcohol exposure and highly radiosensitive tumours. This means they are living longer, often with the debilitating functional side effects of treatment. The primary objective of this study was to determine how virally mediated nasopharyngeal and oropharyngeal cancers respond to radiation therapy treatment. The aim was to determine risk categories and corresponding adaptive treatment management strategies to proactively manage these patients. Method/Results: 121 patients with virally mediated, node positive nasopharyngeal or oropharyngeal cancer who received radiotherapy treatment with curative intent between 2005 and 2010 were studied. Relevant patient demographics including age, gender, diagnosis, TNM stage, pre-treatment nodal size and dose delivered was recorded. Each patient’s treatment plan was reviewed to determine if another computed tomography (re-CT) scan was performed and at what time point (dose/fraction) this occurred. The justification for this re-CT was determined using four categories: tumour and/or nodal regression, weight loss, both or other. Patients who underwent a re-CT were further investigated to determine whether a new plan was calculated. If a re-plan was performed, the dosimetric effect was quantified by comparing dose volume histograms of planning target volumes and critical structures from the actual treatment delivered and the original treatment plan. Preliminary results demonstrated that 25/121 (20.7%) patients required a re-CT and that these re-CTs were performed between fractions 20 to 25 of treatment. The justification for these re-CTs consisted of a combination of tumour and/or nodal regression and weight loss. 16/25 (13.2%) patients had a replan calculated. 9 (7.4%) of these replans were implemented clinically due to the resultant dosimetric effect calculated. The data collected from this assessment was statistically analysed to identify the major determining factors for patients to undergo a re-CT and/or replan. Specific factors identified included nodal size and timing of the required intervention (i.e. how when a plan is to be adapted). This data was used to generate specific risk profiles that will form the basis of a biologically guided adaptive treatment management strategy for virally mediated head and neck cancer. Conclusion: Preliminary data indicates that virally mediated head and neck cancers respond significantly during radiation treatment (tumour and/or nodal regression and weight loss). Implications of this response are the potential underdosing or overdosing of tumour and/or surrounding critical structures. This could lead to sub-optimal patient outcomes and compromised quality of life. Consequently, the development of adaptive treatment strategies that improve organ sparing for this patient group is important to ensure delivery of the prescribed dose to the tumour volume whilst minimizing the dose received to surrounding critical structures. This could reduce side effects and improve overall patient quality of life. The risk profiles and associated adaptive treatment approaches developed in this study will be tested prospectively in the clinical setting in Phase 2 of this investigation.

Natural convection flow in a strong cross magnetic field with radiation

The problem of MHD natural convection boundary layer flow of an electrically conducting and optically dense gray viscous fluid along a heated vertical plate is analyzed in the presence of strong cross magnetic field with radiative heat transfer. In the analysis radiative heat flux is considered by adopting optically thick radiation limit. Attempt is made to obtain the solutions valid for liquid metals by taking Pr≪1. Boundary layer equations are transformed in to a convenient dimensionless form by using stream function formulation (SFF) and primitive variable formulation (PVF). Non-similar equations obtained from SFF are then simulated by implicit finite difference (Keller-box) method whereas parabolic partial differential equations obtained from PVF are integrated numerically by hiring direct finite difference method over the entire range of local Hartmann parameter, $xi$ . Further, asymptotic solutions are also obtained for large and small values of local Hartmann parameter $xi$ . A favorable agreement is found between the results for small, large and all values of $xi$ . Numerical results are also demonstrated graphically by showing the effect of various physical parameters on shear stress, rate of heat transfer, velocity and temperature.

Natural convection flow with surface radiation along a vertical wavy surface

In this study, natural convection boundary layer flow of thermally radiating fluid along a heated vertical wavy surface is analyzed. Here, the radiative component of heat flux emulates the surface temperature. Governing equations are reduced to dimensionless form, subject to the appropriate transformation. Resulting dimensionless equations are transformed to a set of parabolic partial differential equations by using primitive variable formulation, which are then integrated numerically via iterative finite difference scheme. Emphasis has been given to low Prandtl number fluid. The numerical results obtained for the physical parameters, such as, surface radiation parameter, R, and radiative length parameter, ξ, are discussed in terms of local skin friction and Nusselt number coefficients. Comprehensive interpretation of velocity distribution is also given in the form of streamlines.

Conduction-radiation effect on natural convection flow in a fluid-saturated non-Darcy porous medium enclosed by non-isothermal walls

The effect of conduction-convection-radiation on natural convection flow of Newtonian optically thick gray fluid, confined in a non-Darcian porous media square cavity is numerically studied. For the gray fluid consideration is given to Rosseland diffusion approximation. Further assuming that (i) the temperature of the left vertical wall is varying linearly with height, (ii) cooled right vertical and top walls and (iii) the bottom wall is uniformly-heated. The governing equations are solved using the Alternate Direct Implicit method together with the Successive Over Relaxation technique. The investigation of the effect of governing parameters namely the Forschheimer resistance (Γ), the Planck constant (Rd), and the temperature difference (Δ), on flow pattern and heat transfer characteristics has been carried out. It was seen that the reduction of flow and heat transfer occurs as the Forschheimer resistance is increased. On the other hand both the strength of flow and heat transfer increases as the temperature ratio, Δ, is increased.

Applicability of the polysulphone horizontal calibration to differently inclined dosimeters

Polysulphone (PS) dosimetry has been a widely used technique for more than 30 years to quantify the erythemally effective UV dose received by anatomic sites (personal exposure). The calibration of PS dosimeters is an important issue as their spectral response is different from the erythemal action spectrum. It is performed exposing a set of PS dosimeters on a horizontal plane and measuring the UV doses received by dosimeters using calibrated spectroradiometers or radiometers. In this study, data collected during PS field campaigns (from 2004 to 2006), using horizontal and differently inclined dosimeters, were analyzed to provide some considerations on the transfer of the horizontal calibration to differently inclined dosimeters, as anatomic sites usually are. The role of sky conditions, of the angle of incidence between the sun and the normal to the slope, and of the type of surrounding surface on the calibration were investigated. It was concluded that PS horizontal calibrations apply to differently inclined dosimeters for incidence angles up to approximately 70 degrees and for surfaces excluding ones with high albedo. Caution should be used in the application of horizontal calibrations for cases of high-incidence angle and/or high albedo surfaces.

A snapshot of radiation therapy techniques and technology in Queensland : an aid to mapping undergraduate curriculum

Introduction: Undergraduate students studying the Bachelor of Radiation Therapy at Queensland University of Technology (QUT) attend clinical placements in a number of department sites across Queensland. To ensure that the curriculum prepares students for the most common treatments and current techniques in use in these departments, a curriculum matching exercise was performed. Methods: A cross-sectional census was performed on a pre-determined “Snapshot” date in 2012. This was undertaken by the clinical education staff in each department who used a standardized proforma to count the number of patients as well as prescription, equipment, and technique data for a list of tumour site categories. This information was combined into aggregate anonymized data. Results: All 12 Queensland radiation therapy clinical sites participated in the Snapshot data collection exercise to produce a comprehensive overview of clinical practice on the chosen day. A total of 59 different tumour sites were treated on the chosen day and as expected the most common treatment sites were prostate and breast, comprising 46% of patients treated. Data analysis also indicated that intensity-modulated radiotherapy (IMRT) use is relatively high with 19.6% of patients receiving IMRT treatment on the chosen day. Both IMRT and image-guided radiotherapy (IGRT) indications matched recommendations from the evidence. Conclusion: The Snapshot method proved to be a feasible and efficient method of gathering useful

Standardising radiation therapy undergraduate competency levels

QUT Bachelor of Radiation Therapy students progress from first visiting a radiation therapy department to graduation and progression into the NPDP over a span of three years. Although there are clear guidelines as to expected competency level post-NPDP, there is still a variety of perceived levels prior to this. Staff and students feedback both suggest that different centres and within centres different staff have differing opinions of these levels. Indeed, many staff members object to the use of the word “competency” for a pre-NPODP undergraduate, preferring the term “achievement”. While it is acknowledged that students progress at different rates, it is vitally important for equity that staff expectations of students at different academic levels are identical. Provision of guidelines for different stages of progression are essential for equitable assessment and most assessments, including the NRTAT are complemented by statements to enable level to be determined. For the University-specific competency assessments some level of consensus between clinical staff is required, especially where students are placed at a large number of different placement sites. Aims The main aim of this initial study is to gauge staff opinions of levels of student progression in order to judge cross-centres consistency. A secondary objective is to evaluate the degree of correlation between staff seniority and perception of student levels. Informal feedback suggests that staff at or just post NPDP level have a different perception of student competency expectations than more senior staff. If these perceptions change with level it will make agreement of guidelines statements more challenging. Study Methods A standard evaluation questionnaire was provided to RT staff participating in ongoing updates to clinical assessment. As part of curriculum development staff were asked to provide anonymous and optional answers to further questions in order to audit current practice. This involved assigning level of student progression to different statements relating to tasks or competencies. After data collation, scores were assigned to level and totals used to rank statements according to perceived student level. Descriptive statistical analysis was used to identify which statements were easier to assign to student level and which were more ambiguous. Further sub-analysis was performed for each category of staff seniority to judge differences in perception. Strength of correlation between seniority and expectation was calculated to confirm or contradict the informal feedback. Results By collating different staff perceptions of competencies for different student levels commonly agreed statements can be used to define achievement level. This presentation outlines the results of the audit including statements that most staff perceived as relevant to a specific student group and statements that staff found to be harder to attribute. Strength of correlation between staff perception and seniority will be outlined where statistically significant.

Interobserver variability of radiation therapists aligning to fiducial markers for prostate radiation therapy

As the use of fiducial markers (FMs) for the localisation of the prostate during external beam radiation therapy (EBRT) has become part of routine practice, radiation therapists (RTs) have become increasingly responsible for online image interpretation. The aim of this investigation was to quantify the limits of agreement (LoA) between RTs when localising to FMs with orthogonal kilovoltage (kV) imaging. Methods Six patients receiving prostate EBRT utilising FMs were included in this study. Treatment localisation was performed using kV imaging prior to each fraction. Online stereoscopic assessment of FMs, performed by the treating RTs, was compared with the offline assessment by three RTs. Observer agreement was determined by pairwise Bland-Altman analysis. Results Stereoscopic analysis of 225 image pairs was performed online at the time of treatment, and offline by three RT observers. Eighteen pairwise Bland-Altman analyses were completed to assess the level of agreement between observers. Localisation by RTs was found to be within clinically acceptable 95% LoAs. Conclusions Small differences between RTs, in both the online and offline setting, were found to be within clinically acceptable limits. RTs were able to make consistent and reliable judgements when matching FMs on planar kV imaging.

Individual, environmental, and meteorological predictors of daily personal ultraviolet radiation exposure measurements in a United States cohort study

Background Individual exposure to ultraviolet radiation (UVR) is challenging to measure, particularly for diseases with substantial latency periods between first exposure and diagnosis of outcome, such as cancer. To guide the choice of surrogates for long-term UVR exposure in epidemiologic studies, we assessed how well stable sun-related individual characteristics and environmental/meteorological factors predicted daily personal UVR exposure measurements. Methods We evaluated 123 United States Radiologic Technologists subjects who wore personal UVR dosimeters for 8 hours daily for up to 7 days (N = 837 days). Potential predictors of personal UVR derived from a self-administered questionnaire, and public databases that provided daily estimates of ambient UVR and weather conditions. Factors potentially related to personal UVR exposure were tested individually and in a model including all significant variables. Results The strongest predictors of daily personal UVR exposure in the full model were ambient UVR, latitude, daily rainfall, and skin reaction to prolonged sunlight (R2 = 0.30). In a model containing only environmental and meteorological variables, ambient UVR, latitude, and daily rainfall were the strongest predictors of daily personal UVR exposure (R2 = 0.25). Conclusions In the absence of feasible measures of individual longitudinal sun exposure history, stable personal characteristics, ambient UVR, and weather parameters may help estimate long-term personal UVR exposure.

A 250 μg/week dose of vitamin D was as effective as a 50 μg/d dose in healthy adults, but a regimen of four weekly followed by monthly doses of 1250 μg raised the risk of hypercalciuria

The risk of vitamin D insufficiency is increased in persons having limited sunlight exposure and dietary vitamin D. Supplementation compliance might be improved with larger doses taken less often, but this may increase the potential for side effects. The objective of the present study was to determine whether a weekly or weekly/monthly regimen of vitamin D supplementation is as effective as daily supplementation without increasing the risk of side effects. Participants were forty-eight healthy adults who were randomly assigned for 3 months to placebo or one of three supplementation regimens: 50 μg/d (2000 IU/d, analysed dose 70 μg/d), 250 μg/week (10 000 IU/week, analysed dose 331 μg/week) or 1250 μg/week (50 000 IU/week, analysed dose 1544 μg/week) for 4 weeks and then 1250 μg/month for 2 months. Daily and weekly doses were equally effective at increasing serum 25-hydroxyvitamin D, which was significantly greater than baseline in all the supplemented groups after 30 d of treatment. Subjects in the 1250 μg treatment group, who had a BMI >26 kg/m2, had a steady increase in urinary Ca in the first 3 weeks of supplementation, and, overall, the relative risk of hypercalciuria was higher in the 1250 μg group than in the placebo group (P= 0·01). Although vitamin D supplementation remains a controversial issue, these data document that supplementing with ≤ 250 μg/week ( ≤ 10 000 IU/week) can improve or maintain vitamin D status in healthy populations without the risk of hypercalciuria, but 24 h urinary Ca excretion should be evaluated in healthy persons receiving vitamin D3 supplementation in weekly single doses of 1250 μg (50 000 IU).

Faster Monte Carlo simulation of radiotherapy geometries

Using Monte Carlo simulation for radiotherapy dose calculation can provide more accurate results when compared to the analytical methods usually found in modern treatment planning systems, especially in regions with a high degree of inhomogeneity. These more accurate results acquired using Monte Carlo simulation however, often require orders of magnitude more calculation time so as to attain high precision, thereby reducing its utility within the clinical environment. This work aims to improve the utility of Monte Carlo simulation within the clinical environment by developing techniques which enable faster Monte Carlo simulation of radiotherapy geometries. This is achieved principally through the use new high performance computing environments and simpler alternative, yet equivalent representations of complex geometries. Firstly the use of cloud computing technology and it application to radiotherapy dose calculation is demonstrated. As with other super-computer like environments, the time to complete a simulation decreases as 1=n with increasing n cloud based computers performing the calculation in parallel. Unlike traditional super computer infrastructure however, there is no initial outlay of cost, only modest ongoing usage fees; the simulations described in the following are performed using this cloud computing technology. The definition of geometry within the chosen Monte Carlo simulation environment - Geometry & Tracking 4 (GEANT4) in this case - is also addressed in this work. At the simulation implementation level, a new computer aided design interface is presented for use with GEANT4 enabling direct coupling between manufactured parts and their equivalent in the simulation environment, which is of particular importance when defining linear accelerator treatment head geometry. Further, a new technique for navigating tessellated or meshed geometries is described, allowing for up to 3 orders of magnitude performance improvement with the use of tetrahedral meshes in place of complex triangular surface meshes. The technique has application in the definition of both mechanical parts in a geometry as well as patient geometry. Static patient CT datasets like those found in typical radiotherapy treatment plans are often very large and present a significant performance penalty on a Monte Carlo simulation. By extracting the regions of interest in a radiotherapy treatment plan, and representing them in a mesh based form similar to those used in computer aided design, the above mentioned optimisation techniques can be used so as to reduce the time required to navigation the patient geometry in the simulation environment. Results presented in this work show that these equivalent yet much simplified patient geometry representations enable significant performance improvements over simulations that consider raw CT datasets alone. Furthermore, this mesh based representation allows for direct manipulation of the geometry enabling motion augmentation for time dependant dose calculation for example. Finally, an experimental dosimetry technique is described which allows the validation of time dependant Monte Carlo simulation, like the ones made possible by the afore mentioned patient geometry definition. A bespoke organic plastic scintillator dose rate meter is embedded in a gel dosimeter thereby enabling simultaneous 3D dose distribution and dose rate measurement. This work demonstrates the effectiveness of applying alternative and equivalent geometry definitions to complex geometries for the purposes of Monte Carlo simulation performance improvement. Additionally, these alternative geometry definitions allow for manipulations to be performed on otherwise static and rigid geometry.

Calculation of dose kernels for radiotherapy applications using the GEANT 4 Monte Carlo toolkit

Dose kernels may be used to calculate dose distributions in radiotherapy (as described by Ahnesjo et al., 1999). Their calculation requires use of Monte Carlo methods, usually by forcing interactions to occur at a point. The Geant4 Monte Carlo toolkit provides a capability to force interactions to occur in a particular volume. We have modified this capability and created a Geant4 application to calculate dose kernels in cartesian, cylindrical, and spherical scoring systems. The simulation considers monoenergetic photons incident at the origin of a 3 m x 3 x 9 3 m water volume. Photons interact via compton, photo-electric, pair production, and rayleigh scattering. By default, Geant4 models photon interactions by sampling a physical interaction length (PIL) for each process. The process returning the smallest PIL is then considered to occur. In order to force the interaction to occur within a given length, L_FIL, we scale each PIL according to the formula: PIL_forced = L_FIL 9 (1 - exp(-PIL/PILo)) where PILo is a constant. This ensures that the process occurs within L_FIL, whilst correctly modelling the relative probability of each process. Dose kernels were produced for an incident photon energy of 0.1, 1.0, and 10.0 MeV. In order to benchmark the code, dose kernels were also calculated using the EGSnrc Edknrc user code. Identical scoring systems were used; namely, the collapsed cone approach of the Edknrc code. Relative dose difference images were then produced. Preliminary results demonstrate the ability of the Geant4 application to reproduce the shape of the dose kernels; median relative dose differences of 12.6, 5.75, and 12.6 % were found for an incident photon energy of 0.1, 1.0, and 10.0 MeV respectively.

An overview of level I evidence for the management of radiation dermatitis literature

Background: Despite the technologic advances, radiation dermatitis is still a prevalent and distressing symptom in patients with cancer undergoing radiotherapy. Systematic reviews (SRs) are regarded as level I evidence providing direction for clinical practice and guidelines. This overview aims to provide a critical appraisal of SRs published on interventions for the prevention/management of radiation dermatitis. Methodology: We searched the following electronic databases: MEDLINE, CINAHL, EMBASE, and the Cochrane Library (up to Feb 2012). We also hand-searched reference lists of potentially eligible articles and a number of key journals in the area. Two authors screened all potential articles and included eligible SRs. Two authors critically appraised and extracted key findings from the included reviews using the “A Measurement Tool to Assess Systematic Reviews” (AMSTAR). Results: Of 1837 potential titles, six SRs were included. A number of interventions have been reported to be potentially beneficial for managing radiation dermatitis. Interventions evaluated in these reviews included skin care advice, steroidal/non-steroidal topical agents, systematic therapies, modes of radiation delivery, and dressings. However, all the included SRs reported that there is insufficient evidence supporting any single effective intervention. The methodological quality of the included studies varied, and methodological shortfalls in these reviews may create biases to the overall results or recommendations for clinical practice. Conclusions and implications: An up-to-date high quality SR in preventing/managing radiation dermatitis is needed to guide practice and direction for future research. Clinicians or guideline developers are recommended to critically evaluate the information of SRs in their decision making.