Setup Reproducibility Research Articles

Comparative analysis of fetal dose sparing between a C-arm linac and an O-ring linac in a SIB-VMAT sarcoma treatment for a pregnant patient: A technical note and case report.

To compare the effect of two linacs designs on fetal dose sparing on a pregnant patient, including estimation of the fetal dose, and the effect of a lead apron. A patient with a high-grade sarcoma located in the right knee/lower thigh was prescribed 51Gy (1.7Gy/Fx) with a simultaneous-integrated-boost (SIB) of 60Gy to a smaller volume, starting in the 26thgestational week. Volumetric modulated radiation therapy (VMAT) plans with 6MV-FFF were developed using identical dosimetric constraints on a Varian Truebeam Edge with HD-MLC and a Varian Halcyon with double-stacked MLC. Based on patient dimension measurements, an anthropomorphic phantom was constructed using a Rando phantom and saline bags in the patient's Vac-Lok bag. Phantom measurements were performed using OSLDs and TLDs placed at three different planes, corresponding to the pubis, the umbilicus, and the fundus based on patient measurements and projected gestational age, to estimate the fetal dose. Three experimental scenarios were measured, each with CBCT-based image guidance for an accurate, reproducible setup: Edge, Halcyon, and Halcyon with a tri-folded lead apron (0.5mm×3=1.5mmPb) over the phantom abdomen. Plan quality and total MUs are comparable between the Edge and Halcyon plans. The OSLD-measured whole-course dose to the pubis, umbilicus, and fundus were 18.8, 13.1, and 11.7 cGy, respectively, on Halcyon, on average 27.8% lower than Edge. The repeatability within either dosimeter was good, although TLD showed systematically lower doses. Importantly, both dosimetry systems showed a lower measured fetal dose for the Halcyon plan compared with the Edge plan. Adding a tri-folded lead apron over the abdomen did not meaningfully lower the measured dose. In this case study, Halcyon demonstrated a better sparing of out-of-field fetal dose compared to TrueBeam Edge. It was shown that lead aprons do not provide additional fetal dose sparing.

Coalescence investigations in a small‐scale continuously operated setup for bubble column design

AbstractA novel micro‐channel technique for analyzing the coalescence of bubbles and obtaining relevant information for the creation of a coalescence database is presented. The micro‐channel improves the coalescence investigations by a continuously operated setup, reduces the accumulation of impurities and increases the amount of recorded data. To introduce the new setup, studies with alcoholic, electrolytic aqueous systems and liquid silicone oil as a second liquid are presented, showing the influence of different concentrations. Artificial intelligence has been successfully developed to automate data generation. This approach improves the understanding of bubble coalescence by introducing a reproducible setup. Furthermore, it facilitates the transition to a predictive column design through data‐based decisions and modelling.

A robust index for metal artifact quantification in computed tomography.

Objective assessment of metal artifact strength and the effectiveness of metal artifact reduction algorithms in computed tomography requires a quantitative metric. Metrics described in the literature are typically employed to compare the artifact strength in images reconstructed from the same raw data, but their robustness against varying scan conditions and repeated scans over time as it occurs in periodic quality assurance has not been investigated. A new robust metric for quantifying metal artifacts in computed-tomography images is proposed and compared to other commonly used metrics. The proposed artifact metric is based on the location parameter of the Gumbel distribution, described previously in the literature, but normalized to the location parameter in a background region-of-interest to obtain a noise-independent artifact metric. The metric was compared to three other quantitative metal artifact metrics (artifact-index, contrast-to-noise ratio, Gumbel-evaluation method) by evaluating metals artifacts in phantom scans and in clinical images. Robustness of the artifact metrics was evaluated using repeated scans with varying noise and against small variations in the selected regions-of-interest. The proposed artifact metric was independent of the underlying image noise and could be reproduced more consistently under slight changes of the region-of-interest within the artifact than the other investigated methods. The coefficient-of-variation was 5.7% on average with varying regions-of-interest in phantom scans and 2.5% in patient scans compared to 9.2% in phantoms scans and 9.9% in patient scans for the next-best performing noise-independent metric. Setup reproducibility was better than 5% and was comparable to the other metrics. The new metric correlated linearly with the artifact strength. The contrast-to-noise ratio, although often used in artifact quantification, was found to be an inadequate metric due to its lack of robustness against minute changes in the position, size, and pixel values of the region-of-interest chosen for calculating the metric and because it showed no correlation with the artifact strength. A new metal artifact metric has been proposed that is robust under changing scan conditions and less sensitive to user-dependent choices of the region-of-interest than other metrics. The new metric is straightforward to calculate and simple to implement in software commonly used for evaluation of medical imaging systems.

Air inflow into vacuum-type immobilization devices impacts setup errors.

We aimed to determine the impact of air inflow into vacuum-type immobilization devices (VIDs) on setup errors. We assigned 70 patients undergoing radiotherapy for head and neck cancer to groups V (n = 34) or N (n = 36) according to whether the VIDs were deflated weekly or not deflated during treatment, respectively. We calculated systematic errors (Σ) as the standard deviations (SDs) of mean errors, and random errors (σ) as the root mean square of SDs in each patient. We compared overall means (μ), SDs (SDoverall), random errors and systematic errors. We also measured temporary pressure changes in VIDs to determine the influence of pressure changes in VIDs on setup errors. The μ was within 0.20mm and 0.2° in both groups, whereas SDoverall significantly differed between them. The SDoverall differed the most in the Roll axes of groups N (0. 87°) and V (0.58°). The Σ and σ values were lower in all axes of group V than in group N. Despite the initial deflation target of -70kPa, the pressure in VIDs reached -5kPa at the end of treatment. However, weekly deflation apparently maintained pressure at -20kPa. Effective pressure control in VIDs can reduce patient-by-patient variation and improve setup reproducibility for individual patients, consequently resulting in small variations among overall setup errors.

A Simulation-Free Replacement Solution for Radiation Therapy Immobilization Devices Using Computer Numerical Control (CNC) -Milled Polystyrene Molds

In radiation therapy (RT), if an immobilization device is lost or damaged, the patient may need to be brought back for resimulation, device fabrication, and treatment planning, causing additional imaging radiation exposure, inconvenience, cost, and delay. We describe a simulation-free method for replacing lost or damaged RT immobilization devices. Replacement immobilization devices were fabricated using existing simulation scans as design templates by computer numerical control (CNC) milling of molds made from extruded polystyrene (XPS). XPS material attenuation and bolusing properties were evaluated, a standard workflow was established, and 12 patients were treated. Setup reproducibility was analyzed postfacto using Dice similarity coefficient (DSC) and mean distance to agreement (MDA) calculations comparing onboard treatment imaging with computed tomography (CT) simulations. Results showed that XPS foam material had less dosimetric impact (attenuation and bolusing) than materials used for our standard immobilization devices. The average direct cost to produce each replacement mold was $242.17, compared with over $2000 for standard resimulation. Hands-on time to manufacture was 86.3 minutes, whereas molds were delivered in as little as 4 hours and mostly within 24 hours, compared with a week or more required for standard resimulation. Each mold was optically scanned after production and was measured to be within 2-mm tolerance (pointwise displacement) of design input. All patients were successfully treated using the CNC-milled foam mold replacements, and pretreatment imaging verified satisfactory clinical setup reproduction for each case. The external body contours from the setup cone beam CT and the original CT simulation with matching superior-inferior extent were compared by calculating the DSC and MDA. DSC average was 0.966 (SD, 0.011), and MDA average was 2.694 mm (SD, 0.986). CNC milling of XPS foam is a quicker and more convenient solution than traditional resimulation for replacing lost or damaged RT immobilization devices. Satisfactory patient immobilization, low dosimetric impact compared with standard immobilization devices, and strong correlation of onboard contours with CT simulations are shown. We share our clinical experience, workflow, and manufacturing guide to help other clinicians who may want to adopt this solution.

Novel 3D printed universal conical holder for eye plaque quality assurance

For the custom-built construction of eye plaques, the iodine (I-125) seeds of different source strengths are recycled in our eye plaque program. To return I-125 seeds to the correct lot, we developed a novel 3D-printed conical plaque QA holder for relative assay for eye plaques. A universal 3D-printed conical plaque holder was designed to accommodate six plaque sizes and fit reproducibly in a well-type dose calibrator. A reproducibility test was used to compare the plaque placement consistency in the holder versus without the holder. Plaque assays were performed for assembled plaques both before implant and after explant. The explant reading was compared with the implant reading adjusted for decay, and the relative error was calculated. The plaque response fraction (PRF) is defined as the fraction of well chamber implant reading over the total seed strength for a plaque. The PRF was aggregated for each individual plaque to confirm the seed lot before implant. The reproducibility test showed the chamber reading's relative standard deviation of 0.40% with the QA holder compared to 0.68% without it. The batch relative assay was performed for 251 plaques. The absolute value of measurement deviation between explant and decay-corrected implant readings is 0.89%±0.86% (mean±standard deviation). The PRFs for individual plaques range from 36.49% to 49.87%, with a maximum standard deviation of 2%. This novel 3D-printed QA holder provides reproducible setup for assaying assembled eye plaques in a well chamber. Batch relative assay can validate the seed batch used and plaque integrity during the implant without assaying individual seeds, saving valuable physicist time and radiation exposure from seed handling.

Evaluation of radiation detectors for the determination of field output factors in Leksell Gamma Knife dosimetry using 3D printed phantom inserts

The Leksell Gamma Knife® Perfexion™ and Icon™ have a unique geometry, containing 192 60Co sources with collimation for field sizes of 4 mm, 8 mm, and 16 mm. 4 mm and 8 mm collimated fields lack lateral charged particle equilibrium, so accurate field output factors are essential. This study performs field output factor measurements for the microDiamond, microSilicon, and RAZOR™ Nano detectors.3D printed inserts for the spherical Solid Water® Phantom were fabricated for microDiamond detector, the microSilicon unshielded diode and the RAZOR™ Nano micro-ionisation chamber. Detectors were moved iteratively to identify the peak detector signal for each collimator, representing the effective point of measurement of the chamber.In addition, field output correction factors were calculated for each detector relative to vendor supplied Monte Carlo simulated field output factors and field output factors measured with a W2 scintillator. All field output factors where within 1.1 % for the 4 mm collimator and within 2.3 % for the 8 mm collimator.The 3D printed phantom inserts were suitable for routine measurements if the user identifies the effective point of measurement, and ensures a reproducible setup by marking the rotational alignment of the cylindrical print. Measurements with the microDiamond and microSilicon can be performed faster compared to the RAZOR™ Nano due to differences in the signal to noise ratio. All detectors are suitable for field output factor measurements for the Leksell Gamma Knife® Perfexion™ and Icon™.

Development and characterization of the first proton minibeam system for single-gantry proton facility.

Minibeam represents a preclinical spatially fractionated radiotherapy modality with great translational potential. The advantage lies in its high therapeutic index (compared to GRID and LATTICE) and ability to treat at greater depth (compared to microbeam). Proton minibeam radiotherapy (pMBRT) is a synergy of proton and minibeam. While the single-gantry proton facility has gained popularity due to its affordability and compact design, it often has limited beam time available for research purposes. Conversely, given the current requirement of pMBRT on specific minibeam hardware collimators, necessitates a reproducible and fast setup to minimize pMBRT treatment time and streamline the switching time between pMBRT and conventional treatment for clinically translation. The contribution of this work is the development and characterization of the first pMBRT system tailored for single-gantry proton facility. The system allows for efficient and reproducible plug-and-play setup, achievable within minutes. The single room pMBRT system is constructed based on IBA ProteusONE proton machine. The end of nozzle is attached with beam modifying accessories though an accessory drawer. A small snout is attached to the accessory drawer and used to hold apertures and range shifters. The minibeam aperture consists of two components: a fitting ring and an aperture body. Three minibeam apertures were manufactured. The first-generation apertures underwent qualitatively analysis with film, and the second generation aperture underwent more comprehensive quantitative measurement. The reproducibility of the setup is accessed, and the film measurements are performed to characterize the pMBRT system in cross validation with Monte Carlo (MC) simulations. We presented initial results of large field pMBRT aperture and the film measurements indicates the effect of source-to-isocenter distance=930cm in Y proton scanning direction. Consistent with TOPAS MC simulation, the dose uniformity of pMBRT field<2cm is demonstrated to be better than 2%, rendering its suitability for pre-clinical studies. Subsequently, we developed the second generation of aperture with five slits and characterized the aperture with film dosimetry studies and compared the results to the benchmark MC. Comprehensive film measurements were also performed to evaluate the effect of divergence, air gap and gantry-angle dependency and repeatability and revealing a consistent performance within 5%. Furthermore, the 2D gamma analysis indicated a passing rate exceeding 99% using 3% dose difference and 0.2mm distance agreement criteria. We also establish the peak valley dose ratio and the depth dose profile measurements, and the results are within 10% from MC simulation. We have developed the first pMBRT system tailored for a single-gantry proton facility, which has demonstrated accuracy in benchmark with MC simulations, and allows for efficient plug-and-play setup, emphasizing efficiency.

Feasibility of a Novel Surface-Guided Setup Technique to Reproduce Neck Curvature Using two Regions of Interest.

To improve the setup reproducibility of neck curvature using real-time optical surface imaging (OSI) guidance on 2 regions of interest (ROIs) to infer cervical spine (c-spine) curvature for surface-guided radiotherapy (SGRT) of head-and-neck (HN) and c-spine cancer. A novel SGRT setup approach was designed to reproduce neck curvature with 2 ROIs: upper-chest ROI and open-face ROI. It was hypothesized that the neck curvature could be reproduced if both ROIs were aligned within ±3 mm/2˚ tolerance. This was tested prospectively in 7 volunteers using real-time 3D-OSI guidance and lateral 2D-photography verification after the 3D and 2D references were captured from the initial conventional setup. Real-time SGRT was performed to align chest-ROI and face-ROI, and the longitudinal distance between them was adjustable using a head-support slider. Verification of neck curvature anteriorly and posteriorly was achieved by overlaying edge-extracted lateral pictures. Retrospectively, the relationship between anterior surface and spinal canal alignment was checked in 11 patients using their simulation CT (simCT) and setup cone-beam CT (CBCT). After the anterior surface was rigidly aligned, the spinal canal alignment was checked and quantified using the mean-distance-to-agreement (MDA) and DICE similarity index, and surface-to-spine correlation was calculated. The reproducibility of neck curvatures using the 2xROI SGRT setup is verified and the mean neck-outline-matching difference is within ±2 mm in lateral photographic overlays. The chest-ROI alignment takes 110 ± 58 s and the face-ROI takes 60 ± 35 s. When the anterior body surface is aligned (MDA = 1.1 ± 0.6 mm, DICE = 0.96 ± 0.02,) the internal spinal canal is also aligned (MDA = 1.0 ± 0.3 mm, DICE = 0.84 ± 0.04) in 11 patients. The surface-to-spine correlation is c = 0.90 (MDA) and c = 0.85 (DICE). This study demonstrates the feasibility of the novel 2-ROI SGRT setup technique to achieve reproducible neck and c-spine curvature regardless of neck visibility and availability as ROI. Staff training is needed to adopt this unconventional SGRT technique to improve patient setup.

Natural Language Processing Applied to Forensics Information Extraction With Transformers and Graph Visualization

Digital forensics analysis is a slow process mainly due to the large amount and variety of data. Some forensic tools help categorize files by type and allow automatization of tasks, like named entity recognition (NER). NER is a key component in many natural language processing (NLP) applications, such as relation extraction (RE) and information retrieval. The introduction of neural networks and transformer architectures in the last few years made it possible to develop more accurate models in different languages. This work proposes a reproducible setup to build a forensic pipeline for information extraction using NLP of texts. Our results show that it is possible to develop both NER and RE models in any language and tune its hyper-parameters to achieve state-of-art performance and build comprehensive knowledge graphs, decreasing the amount of time required for human supervision and review. We also find that solving this task in phases can further improve the performance, not only for digital investigation applications, but also for general-purpose information extraction and analysis.

Pre-analytical properties of different respiratory viruses for PCR-based detection: Comparative analysis of sampling devices and sample stabilization solutions

After the decline of the COVID-19 pandemic, health systems were challenged by the simultaneous prevalence of different respiratory viruses causing a wide overlap in symptoms. This increased the demand for multi-virus diagnostic tests which require suitable pre-analytical workflow solutions in order to receive valid diagnostic results. In this context, the effects of specimen storage duration and temperature on the RNA/DNA copy number stability of influenza A/B, RSV A/B, SARS-CoV-2 and adenovirus were examined for four commercially available transport swab systems and saliva collection devices. The respiratory viruses were more stable in the saliva collection devices than in the transport swab systems when stored at RT or 37 °C for up to 96 h. Moreover, no differences between viral nucleic acid stability of enveloped and non-enveloped viruses were observed. The infectivity of all enveloped viruses could be inactivated by the saliva collection device from PreAnalytiX. The Norgen saliva device completely inactivated influenza A/B, while RSV A/B were partially inactivated. The non-enveloped adenovirus was inactivated by a reduction factor of 10E+ 4 in both saliva collection devices. All respiratory viruses remained infectious in the transport swab systems. Two possible transport medium additives were tested which inactivated or strongly reduced viral replication of tested enveloped viruses but had no effect on the non-enveloped adenovirus. Finally the implementation of multi-target detection procedures involving a direct amplification approach was successfully tested by spike-in of all enveloped viruses simultaneously into transport swab systems. This fast and reproducible setup presents a valuable solution for future implementations in multi-virus testing strategies.

Utilizing MRI, [18F]FDG-PET and [89Zr]Zr-DFO-28H1 FAP-PET tracer to assess inflammation and fibrogenesis in a reproducible lung injury rat model: a multimodal imaging study.

Accurate imaging biomarkers that indicate disease progression at an early stage are highly important to enable timely mitigation of symptoms in progressive lung disease. In this context, reproducible experimental models and readouts are key. Here, we aim to show reproducibility of a lung injury rat model by inducing disease and assessing disease progression by multi-modal non-invasive imaging techniques at two different research sites. Furthermore, we evaluated the potential of fibroblast activating protein (FAP) as an imaging biomarker in the early stage of lung fibrosis. An initial lung injury rat model was set up at one research site (Lund University, Lund, Sweden) and repeated at a second site (Radboudumc, Nijmegen, The Netherlands). To induce lung injury, Sprague-Dawley rats received intratracheal instillation of bleomycin as one single dose (1,000 iU in 200 µL) or saline as control. Thereafter, longitudinal images were acquired to track inflammation in the lungs, at 1 and 2 weeks after the bleomycin challenge by magnetic resonance imaging (MRI) and [18F]FDG-PET. After the final [18F]FDG-PET scan, rats received an intravenous tracer [89Zr]Zr-DFO-28H1 (anti-FAP antibody) and were imaged at day 15 to track fibrogenesis. Upon termination, bronchoalveolar lavage (BAL) was performed to assess cell and protein concentration. Subsequently, the biodistribution of [89Zr]Zr-DFO-28H1 was measured ex vivo and the spatial distribution in lung tissue was studied by autoradiography. Lung sections were stained and fibrosis assessed using the modified Ashcroft score. Bleomycin-challenged rats showed body weight loss and increased numbers of immune cells and protein concentrations after BAL compared with control animals. The initiation and progression of the disease were reproduced at both research sites. Lung lesions in bleomycin-exposed rats were visualized by MRI and confirmed by histology. [18F]FDG uptake was higher in the lungs of bleomycin-challenged rats compared with the controls, similar to that observed in the Lund study. [89Zr]Zr-DFO-28H1 tracer uptake in the lung was increased in bleomycin-challenged rats compared with control rats (p = 0.03). Here, we demonstrate a reproducible lung injury model and monitored disease progression using conventional imaging biomarkers MRI and [18F]FDG-PET. Furthermore, we showed the first proof-of-concept of FAP imaging. This reproducible and robust animal model and imaging experimental set-up allows for future research on new therapeutics or biomarkers in lung disease.

Scalp Volumetric Modulated Arc Therapy Using 3D Milled Bolus: Dosimetry, Toxicity and Outcome.

Radiotherapy for scalp lesions is frequently challenging due to the competing needs for target volume coverage, sparing of numerous critical nearby OARs, and reproducible bolus setup despite the irregular and highly convex scalp geometry. Here, we evaluate the use of 3D milled bolus in treating such tumors. A retrospective analysis of scalp patients (pts) treated between 2016-2022 using 3D milled bolus and VMAT. All pts were treated with 6 MV photon beams, IGRT via daily CBCT, and 6-degree of Freedom (6-DOF) couch tops. Pts demographics, tumor characteristics, DVHs, toxicities and outcomes were evaluated. Regional control (RC) defined as control of the disease in the rest of the scalp/neck and local control (LC) defined as disease control within the PTV. A total of 23 pts were identified. Median age 74 (46-85), ECOG performance status was 0-1 in 20 pts (87%) and 92% were males. The histopathologies were squamous cell carcinoma (SCC) (61%), angiosarcoma (AS) (35%) and melanoma (4%). 35% of pts were treated with definitive intent to gross disease; the remaining 65% were treated post-operatively, 22% with microscopically positive margins and 43% with negative margins. 21% had perineural invasion (PNI), and none had lymphovascular invasion (LVI). 78% had T3/T4 and 13% had N+ disease. Median radiation dose was 66 Gy (60-69.96Gy). 44% received concurrent systemic therapy (Paclitaxel 22%, Cemiplimab 12%, Temozolomide 5%, Nivolumab 5%). In 40% of pts, the whole scalp was treated; in the remaining 60%, the median ratio of PTV volume to scalp volume was 35% (25-90%). 22% of pts (n = 5) had neck irradiation for prophylactic (3pts)/ neck lymph node involvement (2 pts). The median brain Dmax was 65 Gy (52.5-71.9), median brain mean dose was 15.4Gy (1.4-38.4), median eye Dmax was 10.9Gy (0.23-49), median cochlea mean was 8.4Gy (0.1-20.4), median lacrimal gland mean dose was 6.8Gy (0.11-38), median hippocampus Dmin was 5.9Gy (0.1-14.9) and Dmax was 10Gy (0.3-23). Most common acute side effects were grade 1-2 fatigue (100%), grade 1-2 pain (78%), grade 1 dysgeusia (22%), grade 1-2 dermatitis (74%). The only grade > = 3 adverse event was grade 3 dermatitis in 26%. Regarding long-term side effects, one pt had grade 2 osteoradionecrosis and other one developed grade 2 skin ulcer. 17% developed grade 1 memory impairment. 17% had grade 1 eye dryness. None developed brain radionecrosis. At a median follow-up was 14.4 months (1-73.5), the 1-yr LC was 96%. The 1-yr RC was 75% overall, 100% in angiosarcoma vs 62% in SCC (p = 0.18). Of the 4 regional recurrences, 1 pt had marginal recurrence along V1, 2 had neck nodal recurrence, and 1 had recurrence elsewhere in the scalp. 1-yr DMFS was 62% overall. 1-yr OS was 78% overall, 100% for AS vs 64% for SCC (P = 0.097). VMAT planning with 3D milled bolus permits technically sound radiotherapy for scalp targets with an acceptable toxicity profile and relatively favorable clinical outcomes. This approach warrants further evaluation in a larger prospective study.

Clinical Outcomes and Setup Reproducibility in Patients Receiving Synchronous Bilateral Breast Radiation in the Prone Position

Standardized radiation therapy (RT) positioning and planning are vital to treat both breasts without excess toxicity in patients with synchronous bilateral breast cancer (SBBC). We studied clinical outcomes and setup reproducibility in patients with SBBC treated in the prone position. This is a retrospective study of patients receiving RT for SBBC from 2012-2022 treated in the prone position. Patient demographics, RT dose and field, toxicity, and outcomes were collected. RT planning used gantry and table shifts to avoid entrance/exit through contralateral breast and organs at risk. RT delivery was standardized, with left breast treated first. After 2014, radiographic films were placed during the first 5 fractions to evaluate field overlap. Consistent overlap required re-simulation or re-planning. Positional shifts during setup were collected for patients receiving bilateral whole breast irradiation (WBI) and bilateral partial breast irradiation (PBI). A total of 45 patients were treated for SBBC. Median age was 67 years. Median follow-up was 28 months. 35 patients were treated with WBI (1 with low axilla on one side) and 5 with PBI. 5 patients were treated with WBI in one breast and PBI in the other. The most common whole breast dose was 40.5Gy, with a simultaneous integrated boost to the lumpectomy cavity to 48Gy. PBI patients were treated with 30Gy (n = 4) or 40.05Gy (n = 1). 8 patients (17.7%) had acute grade 2 and 1 patient (2%) had acute grade 3 dermatitis. This patient was treated WBI bilaterally and was known to have overlap on GaF. Physician and patient accepted higher toxicity for adequate coverage of bilateral upper inner quadrant tumors. Patients with grade > = 2 dermatitis had bilateral WBI (+/- low axilla) except 1. 6 patients had acute dermatitis in the sternal area (5 were WBI and 1 PBI). Only 2 of these patients had overlap on GaF. Of 20 patients with late toxicity follow-up (> 6 months), 5 (25%) had late grade 1-2 dermatitis. 4 (20%) were treated with WBI (+/-low axilla). 1 patient had both a local and distant recurrence. For setup and treatment delivery, couch shifts recorded for patients treated with bilateral WBI (n = 33) and bilateral PBI (n = 5) were minimal. Mean shifts in nearly all dimensions were limited to sub-centimeter or sub-degree changes, with 2D and cone beam CT (CBCT) imaging. Analysis of GaF showed that only 3 patients (10%) had field overlap. A new plan was created for 1 patient to increase the gap between fields, and for the others, patient and physician accepted overlap for adequate coverage. To our knowledge, this is the first study examining clinical outcomes and setup reproducibility in patients treated with SBBC in the prone position. This study indicates the feasibility of prone bilateral breast treatment with minimal shifts and overlap on daily treatments. However, we do see a higher number of acute dermatitis in patients treated with bilateral WBI (vs. PBI) and that overlap was not seen on GaF in all patients who developed sternal dermatitis.

Evaluation of Daily Patient Position Accuracy and Calculation of Setup Errors with Skin Markers and Surface-Guided Radiotherapy (SGRT) in Breast Cancer

This study aims to compare the inter-fractional patient positioning errors between the use of skin markers and SGRT in patients receiving breast radiotherapy. It also includes calculating the inter- and intra-fractional PTV margins required for free breathing (FB) and deep inspiration breath-hold (DIBH) techniques due to setup uncertainties. The treatment data of a total of 2209 fractions from 80 patients who received whole breast or chest wall radiotherapy at an institution between March 2021 and December 2022 were retrospectively analyzed. In the first group of patients, the skin markers placed in the Computed Tomography (CT) scan with the FB technique were aligned and positioned with the room lasers in the Elekta Versa HD, and plan-specific shifts were made. The optical surface scanning procedure was applied to the second group of patients with the Sentinel™ system for FB or DIBH techniques in simulation. Patients were positioned for treatment by matching reference surface images with real-time images from the Catalyst™ HD surface imaging system. Positions of all patients were verified with kilovoltage or cone-beam CT imaging systems, and 3D shift vectors were recorded daily. To compare both setup methods, PTV margins including mean positioning shifts (MPS), the vector length of the shifts and setup errors were calculated from van Herk's formulas. The MPS of all patients using skin markers were 0.20±0.85 cm, 0.32±1.55 cm, and 0.18±0.44 cm in the vertical, longitudinal and lateral directions, respectively. Then, these values given above were found to be 0.12±0.15 cm, 0.06±0.17 cm, 0.07±0.23 cm for FB using Catalyst™ HD, and 0.34±0.30 cm, 0.29±0.26 cm, 0.23±0.30 cm for DIBH. In different setup techniques, no statistically significant difference was found between the 3D shift vectors in any direction with Wilcoxon signed-rank test (p>0.05). The mean standard deviation values in all directions were calculated as 1.22 cm and 0.61 cm, respectively, in patients using skin markers and SGRT. This study indicates a significant difference between the positioning shifts of patients positioned with skin markers and SGRT. The surface imaging system is an advantageous non-invasive method that increases setup accuracy and reproducibility in breast radiotherapy.

Feasibility and Clinical Implementation of Electron FLASH Radiation Therapy in the Yorkshire Swine Model

Preclinical studies have shown FLASH radiation therapy (RT) increases the therapeutic index through reduction in normal tissue toxicity but with retained tumor control compared to conventional dose rate (CONV) RT. Dosimetry in FLASH beams is challenging and complex as beam monitoring and proper dosimetry analysis remain uncertain and under investigation. Despite these limitations, clinical translation of FLASH RT has already begun. For translation of FLASH RT from the preclinical stage, it is critical that robust clinical workflows and dosimetry methods be confidently established to ensure patient safety. Here, we present the clinical workflow for the Yorkshire pig, an animal that resembles the body dimension, weight, and biology of a human patient, with the goal to establish standard operating procedures to ensure a safe and robust clinical translation in our upcoming phase I study in cutaneous tumors. The study determines feasibility and safety while finding incidence of dose-limiting toxicities and maximum tolerable dose for future Phase II trials. All procedures were approved by the institutional animal care and use committee. 6 pigs (40-50 kg) were placed under general anesthesia and underwent CT imaging for radiation therapy simulation purposes. The skin was first shaven, and targets on the dorsolateral flanks were marked with tattoos and BBs for CT visualization. Vacloc immobilization was used to allow for reproducible setup on the treatment couch. A treatment planning model was established for treatment planning and dose evaluation purposes. CONV and FLASH single and fractionated dose regimens were prescribed to the 90% isodose line in a 9 MeV beam. Skin collimation and bolus minimized beam penumbra and increased skin dose. Treatment time and pulse repetition frequency were constant between all FLASH fields. Prescription levels were varied via dose per pulse. Calibration and verification of these settings were performed utilizing a multi-dosimeter method for verification in solid water. Output of the beam was verified on the day of the treatment using beam current transformers. This same multi-dosimeter method was used as in-vivo dosimetry on treatment day and compared to the dose verification ensure full dose was received. Variation between the three dosimeter methods was found to be within 5% among all pigs within the study. The maximum percent difference between dose verification and dose delivery was 6%. Consideration must be taken in dosimeter readout error due to the surface of the pig skin. FLASH and CONV toxicity results are currently under evaluation and will be published upon completion of the study. Establishing guidelines and protocols for electron FLASH clinical translation is important to instill confidence in patient safety with this new technique. This study has further optimized and developed dosimetry tools and setup to be used in future clinical trials.

Making Every Single Puff Count-Simple and Sensitive E-Cigarette Aerosol Sampling for GCxIMS and GC-MS Analysis.

The analysis of the aerosol from tobaccoless electronic cigarettes (e-cigarettes) is an important part of understanding their impact on human health, yet sampling aerosol from e-cigarettes is still considered a challenge. It lacks a standard method for research and quality control and there are a variety of methods. However, few are simple and inexpensive, and none have been suggested for the use with gas chromatography coupled ion mobility spectrometry (GCxIMS). This work presents and evaluates such a setup made from standard lab equipment to quickly collect a quantitative sample from the aerosol of a single puff (5 s totaling 125 mL). The aerosol condensates directly in the cooled headspace (HS) vial, which is analyzed in the HS-GCxIMS or mass spectrometer (HS-GC-MS). The combined use of GC-MS and GCxIMS allows the simple and sensitive identification of unknown substances in complex mixtures and the identification of degradation products in the aerosols. A calibration of 26 flavor compounds (0.2-20 µg/g) was created using single puffs of a spiked, flavorless commercial refill solution and 2-alkanones as internal standards. This sensitive but easily reproducible setup enables a wide range of further investigations, even for labs that were previously unable to afford it.

Use of immobilisation bra for daily setup of patients with pendulous breasts undergoing radiotherapy.

Afeasibility study to evaluate the Chabner XRT® Radiation Bra (CIVCO Radiotherapy & Qfix, Coralville, IA, USA) as acustomised immobilisation device for patients with pendulous breasts undergoing radiotherapy was conducted. Atotal of 34patients with large pendulous breasts were fitted with the Chabner XRT® Radiation Bra during RT. Amixed-method questionnaire was administered to both radiation therapists (RTTs) and patients. RTTs evaluated the effectiveness of the bra in setup. Patients appraised its comfort level and ease of wearing. Setup reproducibility was evaluated based on adepartmental imaging protocol. Acute skin side effects were documented with photos and assessed using the Radiation Therapy Oncology Group (RTOG) classification. Of the patients, 27 (79.4%) completed the questionnaire. 23patients felt comfortable wearing the bra while 20 felt less exposed during treatment. Reproducibility was acceptable, with amedian (range) setup error (isocentre) of 0.0 cm (-0.6 to 0.7 cm; left/right), -0.1 cm (-0.5 to 1.2 cm; posterior) and 0.2 cm (-0.5 to 0.9 cm; inferior) achieved based on matched field borders on skin. However, repeated setups and imaging were required for 3patients due to large breast size (cups D-G; size 4-5). Minimal skin toxicity (grade0-1) was observed. No grade ≥ 2 was reported. 10RTTs completed the survey. Male RTTs (n = 4) were not confident in assisting patients with bra fitting. 8RTTs agreed that although it was difficult to reproduce the breast tissue for treatment, it helped patients to maintain the treatment position. Our study demonstrated the feasibility of using acustomised bra which provided optimal setup reproducibility while maintaining minimal skin toxicity and patient comfort, especially the value-added modesty felt among Asian women during their breast cancer radiotherapy.

Maintaining Skeletal Traction During CT Scans: A Novel and Reproducible Setup

Introduction: Skeletal traction is an integral technique in orthopedic fracture management, used primarily in the acute preoperative setting, but in many parts of the world, is still considered for definitive management. Maintenance of skeletal traction during imaging procedures can be a large burden on providers, and releasing traction even for a short period of time can have significant adverse outcomes for patients. There is currently no practical technique for accomplishing this in the literature. Materials and Methods: We describe here a novel and easily reproducible setup that allows for the maintenance of traction during computed tomography scans. Results: The described technique is versatile as it can be used with different computed tomography scanners, easily assembled in a few minutes, and accommodates up to 25 lbs. Conclusions: This technical design offers a safe and quickly reproducible setup for skeletal traction in unique situations where traction is required during imaging. The apparatus has implications for advanced diagnostic and research-based imaging as well, and all materials should be readily available at any institution frequently performing skeletal traction.

A Novel Setup Technique for Radiation Treatment of a Severely Obese Patient With a Primary Brain Tumor.

Modern external beam radiation therapy (EBRT) techniques rely on the accurate positioning of the patient using the treatment couch. These motorized couches have weight limits that have decreased over time and are not able to support severely obese patients requiring EBRT. We aimed to develop a technique to support obese patients who are above their weight tolerance while accurately delivering radiation treatment to a brain tumor. This technique was used on a patient receiving adjuvant radiation for gliosarcoma, a variant of glioblastoma. The patient was CT scanned, and the 3D conformal radiation therapy plan was created. A custom treatment couch was created using a transport stretcher, Styrofoam, a CT couch-top, and an IMRT board, which allowed for a thermoplastic mask to be used for a reproducible setup. AP and lateral portal films were taken prior to each treatment to confirm the accuracy of the manual daily setup of the patient on the custom couch. The patient received 60 Gy in 30 daily fractions of 3DCRT in a reproducible fashion. The average deviation from the isocenter fell within the 10 mm and 8 mm planning margins applied to the clinical target volume (CTV) for the initial and boost fields, respectively. The average daily shifts in the anterior-posterior (AP) direction for the patient were 7.97 (-16.19 to 12.04) mm and 1.98 mm (-1.1 to 4.3) mm for the initial and boost treatments, respectively. The average daily shifts in the superior-inferior (SI) direction were 2.2 (-5.08 to 9.04) mm and 3.88 (-2.9 to 8.0) mm for the initial and boost treatments, respectively. This novel approach allowed treatment at 60 Gy for a gliosarcoma patient who had previously been denied treatment due to his weight. By utilizing readily available materials within the department, our team was able to create a reproducible setup technique to safely treat the patient.