Pharmacists' readiness and willingness to vaccinate the public in United Arab Emirates community pharmacies: A cross-sectional study.

Background: Pharmacist-administered vaccination is currently implemented in many countries worldwide. It has contributed to increased vaccine access and vaccine uptake. This observational cross-sectional study assessed community pharmacists' willingness, and readiness to administer vaccines to the public in the United Arab Emirates (UAE) and relate it to national and international policies on vaccination. Methods: This research was an online survey of 24-questions that was made available to community pharmacists via social media and WhatsApp. The survey was open for six weeks (from April to June 2022). Descriptive and inferential analysis was performed. Results: The questionnaire was completed by 374 of 575 (65%) respondents. More than half (64.2%) of the respondents agreed or strongly agreed that pharmacists should be able to vaccinate and 68.4% responded that they were willing to administer vaccines if local regulations allowed them to vaccinate. Most (81.8%) expressed willingness to complete training required to be able to administer vaccines in their pharmacies. Logistic regression showed that pharmacists defined as having high readiness were significantly more willing to undergo all essential training to start a vaccination service in their pharmacies than were pharmacists with poor readiness (OR 2.647; 95% CI: 1.518-4.615; p=0.001). High readiness was also significantly associated with agreement on safety of pharmacy-based vaccination (p=0.027). Conclusions: The majority of community pharmacists surveyed showed readiness to commence pharmacy-based vaccination services. Those with high readiness characteristics are amenable to receiving essential training and consider that vaccination in the community pharmacy setting would be safe.

Quantifying risk using FMEA: An alternate approach to AAPM TG-100 for scoring failures and evaluating clinical workflow.

PURPOSE: Renovation of the brachytherapy program at a leading cancer center utilized methods of the AAPM TG-100 report to objectively evaluate current clinical brachytherapy workflows and develop techniques for minimizing the risk of failures, increasing efficiency, and consequently providing opportunities for improved treatment quality. The TG-100 report guides evaluation of clinical workflows with recommendations for identifying potential failure modes (FM) and scoring them from the perspective of their occurrence frequency O, failure severity S, and inability to detect them D. The current study assessed the impact of differing methods to determine the risk priority number (RPN) beyond simple multiplication. METHODS AND MATERIALS: The clinical workflow for a complex brachytherapy procedure was evaluated by a team of 15 staff members, who identified discrete FM using alternate scoring scales than those presented in the TG-100 report. These scales were expanded over all clinically relevant possibilities with care to emphasize mitigation of natural bias for scoring near the median range as well as to enhance the overall scoring-system sensitivity. Based on staff member perceptions, a more realistic measure of risk was determined using weighted functions of their scores. RESULTS: This new method expanded the range of RPN possibilities by a factor of 86, improving evaluation and recognition of safe and efficient clinical workflows. Mean RPN values for each FM decreased by 44% when changing from the old to the new clinical workflow, as evaluated using the TG-100 method. This decreased by 66% when evaluated with the new method. As a measure of the total risk associated with an entire clinical workflow, the integral of RPN values increased by 15% and decreased by 31% with the TG-100 and new methods, respectively. CONCLUSIONS: This appears to be the first application of an alternate approach to the TG-100 method for evaluating the risk of clinical workflows. It exemplifies the risk analysis techniques necessary to rapidly evaluate simple clinical workflows appropriately.

Validation of a Monte Carlo model for multi leaf collimator based electron delivery.

PURPOSE: To develop and validate a Monte Carlo model of the Varian TrueBeam to study electron collimation using the existing photon multi-leaf collimators (pMLC), instead of conventional electron applicators and apertures. MATERIALS AND METHODS: A complete Monte Carlo model of the Varian TrueBeam was developed using Tool for particle simulation (TOPAS) (version 3.1.p3). Vendor-supplied information was used to model the treatment head components and the source parameters. A phase space plane was setup above the collimating jaws and captured particles were reused until a statistical uncertainty of 1% was achieved in the central axis. Electron energies 6, 9, 12, 16, and 20 MeV with a jaw-defined field of 20 × 20 cm2 at iso-center, pMLC-defined fields of 6.8 × 6.8 cm2 and 11.4 × 11.4 cm2 at 80 cm source-to-surface distance (SSD) and an applicator-defined field of 10 × 10 cm2 at iso-center were evaluated. All the measurements except the applicator-defined fields were measured using an ionization chamber in a water tank using 80 cm SSD. The dose difference, distance-to-agreement and gamma index were used to evaluate the agreement between the Monte Carlo calculations and measurements. Contributions of electron scattering off pMLC leaves and inter-leaf leakage on dose profiles were evaluated and compared with Monte Carlo calculations. Electron transport through a heterogeneous phantom was simulated and the resulting dose distributions were compared with film measurements. The validated Monte Carlo model was used to simulate several clinically motivated cases to demonstrate the benefit of pMLC-based electron delivery compared to applicator-based electron delivery. RESULTS: Calculated and measured percentage depth-dose (PDD) curves agree within 2% after normalization. The agreement between normalized percentage depth dose curves were evaluated using one-dimensional gamma analysis with a local tolerance of 2%/1 mm and the %points passing gamma criteria was 100% for all energies. For jaw-defined fields, calculated profiles agree with measurements with pass rates of >97% for 2%/2 mm gamma criteria. Calculated FWHM and penumbra width agree with measurements within 0.4 cm. For fields with tertiary collimation using an pMLC or applicator, the average gamma pass rate of compared profiles was 98% with 2%/2 mm gamma criteria. The profiles measured to evaluate the pMLC leaf scattering agreed with Monte Carlo calculations with an average gamma pass rate of 96.5% with 3%/2 mm gamma criteria. Measured dose profiles below the heterogenous phantom agreed well with calculated profiles and matched within 2.5% for most points. The calculated clinically applicable cases using TOPAS MC and Eclipse TPS for single enface electron beam, electron-photon mixed beam and a matched electron-electron beam exhibited a reasonable agreement in PDDs, profiles and dose volume histograms. CONCLUSION: We present a validation of a Monte Carlo model of Varian TrueBeam for pMLC-based electron delivery. Monte Carlo calculations agreed with measurements satisfying gamma criterion of 1%/1 mm for depth dose curves and 2%/1 mm for dose profiles. The simulation of clinically applicable cases demonstrated the clinical utility of pMLC-based electrons and the use of MC simulations for development of advanced radiation therapy techniques.

Novel and programmatic improvements to the workflow associated with the AccuBoost breast brachytherapy procedure.

PURPOSE: While the noninvasive breast brachytherapy (NIBB) treatment procedure, known as AccuBoost, for breast cancer patients is well established, the treatment quality can be improved by the efficiency of the workflow delivery. A formalized approach evaluated the current workflow through failure modes and effects analysis and generated insight for developing new procedural workflow techniques to improve the clinical treatment process. METHODS AND MATERIALS: AccuBoost treatments were observed for several months while gathering details on the multidisciplinary workflow. A list of possible failure modes for each procedure step was generated and organized by timing within the treatment process. A team of medical professionals highlighted procedural steps that unnecessarily increased treatment time, as well as introduced quality deficiencies involving applicator setup, treatment planning, and quality control checks preceding brachytherapy delivery. Procedural improvements and their impact on the clinical workflow are discussed. RESULTS: The revised clinical workflow included the following key procedural enhancements. Prepatient arrival: Improvement of prearrival preparation requires advance completion of dose calculation documentation with patient-specific setup data. Patient arrival pretreatment: Physicists carry out dwell time calculations and check the plan, while the therapist concurrently performs several checks of the ensuing hardware configuration. TREATMENT: An electronic method to export the associated HDR brachytherapy paperwork to the electronic medical record system with electronic signatures and captured approvals was generated. Posttreatment: The therapist confirms the applicators were appropriately positioned, and treatment was delivered as expected. CONCLUSIONS: The procedural improvements reduced the overall treatment time, improved consistency across users, and eased performance of this special procedure for all participants.

A super-resolution framework for the reconstruction of T2-weighted (T2w) time-resolved (TR) 4DMRI using T1w TR-4DMRI as the guidance.

PURPOSE: The purpose of this study was to develop T2-weighted (T2w) time-resolved (TR) four-dimensional magnetic resonance imaging (4DMRI) reconstruction technique with higher soft-tissue contrast for multiple breathing cycle motion assessment by building a super-resolution (SR) framework using the T1w TR-4DMRI reconstruction as guidance. METHODS: The multi-breath T1w TR-4DMRI was reconstructed by deforming a high-resolution (HR: 2 × 2 × 2 mm3 ) volumetric breath-hold (BH, 20s) three-dimensional magnetic resonance imaging (3DMRI) image to a series of low-resolution (LR: 5 × 5 × 5 mm3 ) 3D cine images at a 2Hz frame rate in free-breathing (FB, 40 s) using an enhanced Demons algorithm, namely [T1BH →FB] reconstruction. Within the same imaging session, respiratory-correlated (RC) T2w 4DMRI (2 × 2 × 2 mm3 ) was acquired based on an internal navigator to gain HR T2w (T2HR ) in three states (full exhalation and mid and full inhalation) in ~5 min. Minor binning artifacts in the RC-4DMRI were automatically identified based on voxel intensity correlation (VIC) between consecutive slices as outliers (VIC < VICmean -σ) and corrected by deforming the artifact slices to interpolated slices from the adjacent slices iteratively until no outliers were identified. A T2HR image with minimal deformation (<1 cm at the diaphragm) from the T1BH image was selected for multi-modal B-Spline deformable image registration (DIR) to establish the T2HR -T1BH voxel correspondence. Two approaches to reconstruct T2w TR-4DMRI were investigated: (A) T2HR →[T1BH →FB]: to deform T2w HR to T1w BH only as T1w TR-4DMRI was reconstructed, and combine the two displacement vector fields (DVFs) to reconstruct T2w TR-4DMRI, and (B) [T2HR ←T1BH ]→FB: to deform T1w BH to T2w HR first and apply the deformed T1w BH to reconstruct T2w TR-4DMRI. The reconstruction times were similar, 8-12 min per volume. To validate the two methods, T2w- and T1w-mapped 4D XCAT digital phantoms were utilized with three synthetic spherical tumors (ϕ = 2.0, 3.0, and 4.0 cm) in the lower or mid lobes as the ground truth to evaluate the tumor location (the center of mass, COM), size (volume ratio, %V), and shape (Dice index). Six lung cancer patients were scanned under an IRB-approved protocol and the T2w TR-4DMRI images reconstructed from the two methods were compared based on the preservation of the three tumor characteristics. The local tumor-contained image quality was also characterized using the VIC and structure similarity (SSIM) indexes. RESULTS: In the 4D digital phantom, excellent tumor alignment after T2HR -T1HR DIR is achieved: ∆COM = 0.8 ± 0.5 mm, %V = 1.06 ± 0.02, and Dice = 0.91 ± 0.03, in both deformation directions using the DIR-target image as the reference. In patients, binning artifacts are corrected with improved image quality: average VIC increases from 0.92 ± 0.03 to 0.95 ± 0.01. Both T2w TR-4DMRI reconstruction methods produce similar tumor alignment errors ∆COM = 2.9 ± 0.6 mm. However, method B ([T2HR ←T1BH ]→FB) produces superior results in preserving more T2w tumor features with a higher %V = 0.99 ± 0.03, Dice = 0.81 ± 0.06, VIC = 0.85 ± 0.06, and SSIM = 0.65 ± 0.10 in the T2w TR-4DMRI images. CONCLUSIONS: This study has demonstrated the feasibility of T2w TR-4DMRI reconstruction with high soft-tissue contrast and adequately-preserved tumor position, size, and shape in multiple breathing cycles. The T2w-centric DIR (method B) produces a superior solution for the SR-based framework of T2w TR-4DMRI reconstruction with highly preserved tumor characteristics and local image features, which are useful for tumor delineation and motion management in radiation therapy.

Automated position and size selection of round applicators for AccuBoost breast brachytherapy.

PURPOSE: AccuBoost is a complex non-invasive brachytherapy procedure for breast treatment. This technique requires a radiation oncologist to manually select applicator grid position and size by overlaying transparencies over a mammographic image to encompass surgical clips and resected tumor bed. An algorithm was developed in MATLAB™ to automate the selection of round applicators based on surgical clip position. MATERIAL AND METHODS: A total of 42 mammograms belonging to 10 patients were retrospectively analyzed. Images were pre-processed by masking imprinted localization grid and regions around the grid. A threshold was applied to isolate high-intensity pixels and generate a binary image. A set of morphological operations including region dilation, filling, clearing border structures, and erosion were performed to segment the different regions. A support vector machine classification model was trained to categorize segmented regions as either surgical clips or miscellaneous objects based on different region properties (area, perimeter, eccentricity, circularity, minor axis length, and intensity-derived quantities). Applicator center position was determined by calculating the centroid of detected clips. Size of the applicator was determined with the smallest circle that encompassed all clips with an isotropic 1.0 cm margin. RESULTS: The clip identification model classified 946 regions, with a sensitivity of 96.6% and a specificity of 98.2%. Applicator position was correctly predicted for 20 of 42 fractions and was within 0.5 cm of physician-selected position for 33 of 42 fractions. Applicator size was correctly predicted for 25 out of 42 fractions. CONCLUSIONS: The proposed algorithm provided a method to quantitatively determine applicator position and size for AccuBoost treatments, and may serve as a tool for independent verifications. The discrepancy between physician-selected and algorithm-predicted determinations of applicator position and size suggests that the methodology may be further improved by considering radiomic features of breast tissue in addition to clip position.

Feasibility study of individualized optimal positioning selection for left-sided whole breast radiotherapy: DIBH or prone.

The deep inspiration breath hold (DIBH) and prone (P) position are two common heart-sparing techniques for external-beam radiation treatment of left-sided breast cancer patients. Clinicians select the position that is deemed to be better for tissue sparing based on their experience. This approach, however, is not always optimum and consistent. In response to this, we develop a quantitative tool that predicts the optimal positioning for the sake of organs at risk (OAR) sparing. Sixteen left-sided breast cancer patients were considered in the study, each received CT scans in the supine free breathing, supine DIBH, and prone positions. Treatment plans were generated for all positions. A patient was classified as DIBH or P using two different criteria: if that position yielded (1) lower heart dose, or (2) lower weighted OAR dose. Ten anatomical features were extracted from each patient's data, followed by the principal component analysis. Sequential forward feature selection was implemented to identify features that give the best classification performance. Nine statistical models were then applied to predict the optimal positioning and were evaluated using stratified k-fold cross-validation, predictive accuracy and receiver operating characteristic (AUROC). For heart toxicity-based classification, the support vector machine with radial basis function kernel yielded the highest accuracy (0.88) and AUROC (0.80). For OAR overall toxicities-based classification, the quadratic discriminant analysis achieved the highest accuracy (0.90) and AUROC (0.84). For heart toxicity-based classification, Breast volume and the distance between Heart and Breast were the most frequently selected features. For OAR overall toxicities-based classification, Heart volume, Breast volume and the distance between ipsilateral lung and breast were frequently selected. Given the patient data considered in this study, the proposed statistical model is feasible to provide predictions for DIBH and prone position selection as well as indicate important clinical features that affect the position selection.

A Magnetic Resonance Imaging-based approach to quantify radiation-induced normal tissue injuries applied to trismus in head and neck cancer.

BACKGROUND AND PURPOSE: In this study we investigated the ability of textures from T1-weighted MRI scans post-contrast (T1wpost) to identify the critical muscle(s) for radiation-induced trismus. MATERIALS AND METHODS: The study included ten cases (Trismus: ≥Grade 1), and ten age-sex-tumor-location-and-stage-matched controls treated with intensity-modulated radiotherapy to 70Gy@2.12Gy in 2005-2009. Trismus status and T1wPost were conducted within one year post-radiotherapy. For the masseter, lateral and medial pterygoids, and temporalis (M/LP/MP/T), 24 textures were extracted (Grey Level Co-Occurrence (GLCM), Histogram, and Shape). Univariate logistic regression with Bootstrapping (1000 populations) was applied to compare the muscle mean dose (Dmean) and textures between cases and controls (ipsilateral muscles); candidate predictors were suggested by an average p≤0.20 across all Bootstrap populations. RESULTS: Dmean to M/LP/MP (p=0.03/0.14/0.09), one MP/T (p=0.12/0.17), and three M (p=0.14-0.19) textures were candidate predictors. Three of these textures were GLCM- and two Histogram textures with the former being generally higher and the latter lower for cases compared to controls. The Dmean to M and MP, and Haralick Correlation (GLCM) of MP presented with the best discriminative ability (area under the receiver-operating characteristic curve: 0.85, 0.77, and 0.78), and the correlation between Dmean and this texture was weak (Spearman's rank correlation coefficient: 0.26-0.27). CONCLUSIONS: Our exploratory study points towards an interplay between the dose to the masseter, and the medial pterygoid together with the local relationship between the mean MRI intensity relative to its variance of the medial pterygoid for radiation-induced trismus. This opens up for exploration of this interplay within the radiation-induced trismus etiology in the larger multi-institutional setting.

Results of a 10-year survey of workload for 10 treatment vaults at a high-throughput comprehensive cancer center.

The workload for shielding purposes of modern linear accelerators (linacs) consists of primary and scatter radiation which depends on the dose delivered to isocenter (cGy) and leakage radiation which depends on the monitor units (MUs). In this study, we report on the workload for 10 treatment vaults in terms of dose to isocenter (cGy), monitor units delivered (MUs), number of treatment sessions (Txs), as well as, use factors (U) and modulation factors (CI) for different treatment techniques. The survey was performed for the years between 2006 and 2015 and included 16 treatment machines which represent different generations of Varian linear accelerators (6EX, 600C, 2100C, 2100EX, and TrueBeam) operating at different electron and x-ray energies (6, 9, 12, 16 and 20 MeV electrons and, 6 and 15 MV x-rays). An institutional review board (IRB) approval was acquired to perform this study. Data regarding patient workload, dose to isocenter, number of monitor units delivered, beam energies, gantry angles, and treatment techniques were exported from an ARIA treatment management system (Varian Medical Systems, Palo Alto, Ca.) into Excel spreadsheets and data analysis was performed in Matlab. The average (± std-dev) number of treatment sessions, dose to isocenter, and number of monitor units delivered per week per machine in 2006 was 119 ± 39 Txs, (300 ± 116) × 102 cGys, and (78 ± 28) × 103 MUs respectively. In contrast, the workload in 2015 was 112 ± 40 Txs, (337 ± 124) × 102 cGys, and (111 ± 46) × 103 MUs. 60% of the workload (cGy) was delivered using 6 MV and 30% using 15 MV while the remaining 10% was delivered using electron beams. The modulation factors (MU/cGy) for IMRT and VMAT were 5.0 (± 3.4) and 4.6 (± 1.6) respectively. Use factors using 90° gantry angle intervals were equally distributed (~0.25) but varied considerably among different treatment techniques. The workload, in terms of dose to isocenter (cGy) and subsequently monitor units (MUs), has been steadily increasing over the past decade. This increase can be attributed to increased use of high dose hypo-fractionated regimens (SBRT, SRS) and the increase in use of IMRT and VMAT, which require higher MUs per cGy as compared to more conventional treatment (3DCRT). Meanwhile, the patient workload in terms of treatment sessions per week remained relatively constant. The findings of this report show that variables used for shielding purposes still fall within the recommendation of NCRP Report 151.

Novel Wavelet-Based Segmentation of Prostate CBCT Images with Implanted Calypso Transponders.

Segmentation of prostate Cone Beam CT (CBCT) images is an essential step towards real-time adaptive radiotherapy (ART). It is challenging for Calypso patients, as more artifacts generated by the beacon transponders are present on the images. We herein propose a novel wavelet-based segmentation algorithm for rectum, bladder, and prostate of CBCT images with implanted Calypso transponders. For a given CBCT, a Moving Window-Based Double Haar (MWDH) transformation is applied first to obtain the wavelet coefficients. Based on a user defined point in the object of interest, a cluster algorithm based adaptive thresholding is applied to the low frequency components of the wavelet coefficients, and a Lee filter theory based adaptive thresholding is applied on the high frequency components. For the next step, the wavelet reconstruction is applied to the thresholded wavelet coefficients. A binary (segmented) image of the object of interest is therefore obtained. 5 hypofractionated Calypso prostate patients with daily CBCT were studied. DICE, Sensitivity, Inclusiveness and ΔV were used to evaluate the segmentation result.

Validation of the Calypso Surface Beacon Transponder.

Calypso L-shaped Surface Beacon transponder has recently become available for clinical applications. We herein conduct studies to validate the Surface Beacon transponder in terms of stability, reproducibility, orientation sensitivity, cycle rate dependence, and respiratory waveform tracking accuracy. The Surface Beacon was placed on a Quasar respiratory phantom and positioned at the isocenter with its two arms aligned with the lasers. Breathing waveforms were simulated, and the motion of the transponder was tracked. Stability and drift analysis: sinusoidal waveforms (200 cycles) were produced, and the amplitudes of phases 0% (inhale) and 50% (exhale) were recorded at each breathing cycle. The mean and standard deviation (SD) of the amplitudes were calculated. Linear least-squares fitting was performed to access the possible amplitude drift over the breathing cycles. Reproducibility: similar setting to stability and drift analysis, and the phantom generated 100 cycles of the sinusoidal waveform per run. The Calypso system's was re-setup for each run. Recorded amplitude and SD of 0% and 50% phase were compared between runs to assess contribution of Calypso electromagnetic array setup variation. Beacon orientation sensitivity: the Calypso tracks sinusoidal phantom motion with a defined angular offset of the beacon to assess its effect on SD and peak-to-peak amplitude. Rate dependence: sinusoidal motion was generated at cycle rates of 1 Hz, .33 Hz, and .2 Hz. Peak-to-peak displacement and SDs were assessed. Respiratory waveform tracking accuracy: the phantom reproduced recorded breathing cycles (by volunteers and patients) were tracked by the Calypso system. Deviation in tracking position from produced waveform was used to calculate SD throughout entire breathing cycle. Stability and drift analysis: Mean amplitude ± SD of phase 0% or 50% were 20.01 ± 0.04 mm and -19.65 ± 0.08 mm, respectively. No clinically significant drift was detected with drift measured as 5.1 × 10-5 mm/s at phase 0% and -6.0 × 10-5 mm/s at phase 50%. Reproducibility: The SD of the setup was 0.06 mm and 0.02 mm for phases 0% and 50%, respectively. The combined SDs, including both setup and intrarun error of all runs at phases 0% and 50%, were 0.07mm and 0.11 mm, respectively. Beacon orientation: SD ranged from 0.032mm to 0.039 mm at phase 0% and from 0.084 mm to 0.096 mm at phase 50%. The SD was found not to vary linearly with Beacon angle in the range of 0° and 15°. A positive systematic error was observed with amplitude 0.07 mm/degree at phase 0% and 0.05 mm/degree at phase 50%. Rate dependence: SD and displacement amplitudes did not vary significantly between 0.2 Hz and 0.33 Hz. At 1 Hz, both 0% and 50% amplitude measurements shifted up appreciably, by 0.72 mm and 0.78mm, respectively. As compared with the 0.33 Hz data, SD at phase 0% was 1.6 times higher and 5.4 times higher at phase 50%. Respiratory waveform tracking accuracy: SD of 0.233 mm with approximately normal distribution in over 134 min of tracking (201468 data points). The Surface Beacon transponder appears to be stable, accurate, and reproducible. Submillimeter resolution is achieved throughout breathing and sinusoidal waveforms.

A multiple-image-based method to evaluate the performance of deformable image registration in the pelvis.

Deformable image registration (DIR) is essential for adaptive radiotherapy (RT) for tumor sites subject to motion, changes in tumor volume, as well as changes in patient normal anatomy due to weight loss. Several methods have been published to evaluate DIR-related uncertainties but they are not widely adopted. The aim of this study was, therefore, to evaluate intra-patient DIR for two highly deformable organs-the bladder and the rectum-in prostate cancer RT using a quantitative metric based on multiple image registration, the distance discordance metric (DDM). Voxel-by-voxel DIR uncertainties of the bladder and rectum were evaluated using DDM on weekly CT scans of 38 subjects previously treated with RT for prostate cancer (six scans/subject). The DDM was obtained from group-wise B-spline registration of each patient's collection of repeat CT scans. For each structure, registration uncertainties were derived from DDM-related metrics. In addition, five other quantitative measures, including inverse consistency error (ICE), transitivity error (TE), Dice similarity (DSC) and volume ratios between corresponding structures from pre- and post- registered images were computed and compared with the DDM. The DDM varied across subjects and structures; DDMmean of the bladder ranged from 2 to 13 mm and from 1 to 11 mm for the rectum. There was a high correlation between DDMmean of the bladder and the rectum (Pearson's correlation coefficient, R p = 0.62). The correlation between DDMmean and the volume ratios post-DIR was stronger (R p = 0.51; 0.68) than the correlation with the TE (bladder: R p = 0.46; rectum: R p = 0.47), or the ICE (bladder: R p = 0.34; rectum: R p = 0.37). There was a negative correlation between DSC and DDMmean of both the bladder (R p = -0.23) and the rectum (R p = -0.63). The DDM uncertainty metric indicated considerable DIR variability across subjects and structures. Our results show a stronger correlation with volume ratios and with the DSC using DDM compared to using ICE and TE. The DDM has the potential to quantitatively identify regions of large DIR uncertainties and consequently identify anatomical/scan outliers. The DDM can, thus, be applied to improve the adaptive RT process for tumor sites subject to motion.

Dose-volume factors correlating with trismus following chemoradiation for head and neck cancer.

BACKGROUND: To investigate the dose-volume factors in mastication muscles that are implicated as possible causes of trismus in patients following treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy for head and neck cancers. MATERIAL AND METHODS: All evaluable patients treated at our institution between January 2004 and April 2009 with chemotherapy and IMRT for squamous cell cancers of the oropharynx, nasopharynx, hypopharynx or larynx were included in this analysis (N = 421). Trismus was assessed using CTCAE 4.0. Bi-lateral masseter, temporalis, lateral pterygoid and medial pterygoid muscles were delineated on axial computed tomography (CT) treatment planning images, and dose-volume parameters were extracted to investigate univariate and multimetric correlations. RESULTS: Forty-six patients (10.9%) were observed to have chronic trismus of grade 1 or greater. From analysis of baseline patient characteristics, toxicity correlated with primary site and patient age. From dose-volume analysis, the steepest dose thresholds and highest correlations were seen for mean dose to ipsilateral masseter (Spearman's rank correlation coefficient Rs = 0.25) and medial pterygoid (Rs = 0.23) muscles. Lyman-Kutcher-Burman modeling showed highest correlations for the same muscles. The best correlation for multimetric logistic regression modeling was with V68Gy to the ipsilateral medial pterygoid (Rs = 0.29). CONCLUSION: Chemoradiation-induced trismus remains a problem particularly for patients with oropharyngeal carcinoma. Strong dose-volume correlations support the hypothesis that limiting dose to the ipsilateral masseter muscle and, in particular, the medial pterygoid muscle may reduce the likelihood of trismus.

The distance discordance metric-a novel approach to quantifying spatial uncertainties in intra- and inter-patient deformable image registration.

Previous methods to estimate the inherent accuracy of deformable image registration (DIR) have typically been performed relative to a known ground truth, such as tracking of anatomic landmarks or known deformations in a physical or virtual phantom. In this study, we propose a new approach to estimate the spatial geometric uncertainty of DIR using statistical sampling techniques that can be applied to the resulting deformation vector fields (DVFs) for a given registration. The proposed DIR performance metric, the distance discordance metric (DDM), is based on the variability in the distance between corresponding voxels from different images, which are co-registered to the same voxel at location (X) in an arbitrarily chosen 'reference' image. The DDM value, at location (X) in the reference image, represents the mean dispersion between voxels, when these images are registered to other images in the image set. The method requires at least four registered images to estimate the uncertainty of the DIRs, both for inter- and intra-patient DIR. To validate the proposed method, we generated an image set by deforming a software phantom with known DVFs. The registration error was computed at each voxel in the 'reference' phantom and then compared to DDM, inverse consistency error (ICE), and transitivity error (TE) over the entire phantom. The DDM showed a higher Pearson correlation (Rp) with the actual error (Rp ranged from 0.6 to 0.9) in comparison with ICE and TE (Rp ranged from 0.2 to 0.8). In the resulting spatial DDM map, regions with distinct intensity gradients had a lower discordance and therefore, less variability relative to regions with uniform intensity. Subsequently, we applied DDM for intra-patient DIR in an image set of ten longitudinal computed tomography (CT) scans of one prostate cancer patient and for inter-patient DIR in an image set of ten planning CT scans of different head and neck cancer patients. For both intra- and inter-patient DIR, the spatial DDM map showed large variation over the volume of interest (the pelvis for the prostate patient and the head for the head and neck patients). The highest discordance was observed in the soft tissues, such as the brain, bladder, and rectum, due to higher variability in the registration. The smallest DDM values were observed in the bony structures in the pelvis and the base of the skull. The proposed metric, DDM, provides a quantitative tool to evaluate the performance of DIR when a set of images is available. Therefore, DDM can be used to estimate and visualize the uncertainty of intra- and/or inter-patient DIR based on the variability of the registration rather than the absolute registration error.

Treatment planning constraints to avoid xerostomia in head-and-neck radiotherapy: an independent test of QUANTEC criteria using a prospectively collected dataset.

PURPOSE: The severe reduction of salivary function (xerostomia) is a common complication after radiation therapy for head-and-neck cancer. Consequently, guidelines to ensure adequate function based on parotid gland tolerance dose-volume parameters have been suggested by the QUANTEC group and by Ortholan et al. We perform a validation test of these guidelines against a prospectively collected dataset and compared with a previously published dataset. METHODS AND MATERIALS: Whole-mouth stimulated salivary flow data from 66 head-and-neck cancer patients treated with radiotherapy at the British Columbia Cancer Agency (BCCA) were measured, and treatment planning data were abstracted. Flow measurements were collected from 50 patients at 3 months, and 60 patients at 12-month follow-up. Previously published data from a second institution, Washington University in St. Louis (WUSTL), were used for comparison. A logistic model was used to describe the incidence of Grade 4 xerostomia as a function of the mean dose of the spared parotid gland. The rate of correctly predicting the lack of xerostomia (negative predictive value [NPV]) was computed for both the QUANTEC constraints and Ortholan et al. recommendation to constrain the total volume of both glands receiving more than 40 Gy to less than 33%. RESULTS: Both datasets showed a rate of xerostomia of less than 20% when the mean dose to the least-irradiated parotid gland is kept to less than 20 Gy. Logistic model parameters for the incidence of xerostomia at 12 months after therapy, based on the least-irradiated gland, were D(50) = 32.4 Gy and and γ = 0.97. NPVs for QUANTEC guideline were 94% (BCCA data), and 90% (WUSTL data). For Ortholan et al. guideline NPVs were 85% (BCCA) and 86% (WUSTL). CONCLUSION: These data confirm that the QUANTEC guideline effectively avoids xerostomia, and this is somewhat more effective than constraints on the volume receiving more than 40 Gy.

Normal Tissue Complication Probability (NTCP) modeling of late rectal bleeding following external beam radiotherapy for prostate cancer: A Test of the QUANTEC-recommended NTCP model.

PURPOSE/BACKGROUND: Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). MATERIAL AND METHODS: One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. RESULTS: Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ(2) test (p = 0.44). CONCLUSIONS: Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose distribution characteristics do not vary greatly within this patient cohort.

Nickel-based 3D electrocatalyst layers for production of hydrogen by water electrolysis in an acidic medium.

Electrocatalytic activity of three-dimensional nickel-based layers in the hydrogen evolution reaction (HER) was investigated in an acidic medium. It was demonstrated that patterning of a glassy carbon electrode substrate with a 3D polyaniline (PANI) matrix is a convenient way of increasing the electrocatalytically active surface area of electrodeposited Ni, and hence its apparent electrocatalytic activity. The optimized PANI/Ni electrocatalyst layer showed a significantly higher activity in the HER then a two-dimensional control Ni-plate surface. It was also demonstrated that it is possible to produce a Ni-based HER electrocatalyst layer by synthesizing Ni nanoparticles and supporting them on Vulcan carbon. This electrocatalyst also offered a significantly higher electrocatalytic activity in the HER then the control surface, but lower then the optimized PANI/Ni electrocatalyst. The electrocatalytic activity of the optimized PANI/Ni layer was also compared to the activity of a 3D catalyst produced by coating a porous RVC cube substrate with Ni. This electrocatalyst showed the highest HER electrocatalytic activity among the investigated layers when tested under potentiodynamic polarization conditions. However, under the potentiostatic conditions, the optimized PANI/Ni layer showed the highest electrocatalytic activity.