Preclinical Ultra-High Dose Rate (FLASH) Proton Radiation Therapy System for Small Animal Studies.

Purpose: Animal studies with ultrahigh dose-rate radiation therapy (FLASH, >40 Gy/s) preferentially spare normal tissues without sacrificing antitumor efficacy compared with conventional dose-rate radiation therapy (CONV). At the University of Washington, we developed a cyclotron-generated preclinical scattered proton beam with FLASH dose rates. We present the technical details of our FLASH radiation system and preliminary biologic results from whole pelvis radiation. Methods and Materials: A Scanditronix MC50 compact cyclotron beamline has been modified to produce a 48.7 MeV proton beam at dose rates between 0.1 and 150 Gy/s. The system produces a 6 cm diameter scattered proton beam (flat to ± 3%) at the target location. Female C57BL/6 mice 5 to 6 weeks old were used for all experiments. To study normal tissue effects in the distal colon, mice were irradiated using the entrance region of the proton beam to the whole pelvis, 18.5 Gy at different dose rates: control, CONV (0.6-1 Gy/s) and FLASH (50-80 Gy/s). Survival was monitored daily and EdU (5-ethynyl-2´-deoxyuridine) staining was performed at 24- and 96-hours postradiation. Cleaved caspase-3 staining was performed 24-hours postradiation. To study tumor control, allograft B16F10 tumors were implanted in the right flank and received 18 Gy CONV or FLASH proton radiation. Tumor growth and survival were monitored. Results: After 18.5 Gy whole pelvis radiation, survival was 100% in the control group, 0% in the CONV group, and 44% in the FLASH group (P < .01). EdU staining showed cell proliferation was significantly higher in the FLASH versus CONV group at both 24-hours and 96-hours postradiation in the distal colon, although both radiation groups showed decreased proliferation compared with controls (P < .05). Lower cleaved caspase-3 staining was seen in the FLASH versus conventional group postradiation (P < .05). Comparable flank tumor control was observed in the CONV and FLASH groups. Conclusions: We present our preclinical FLASH proton radiation system and biologic results showing improved survival after whole pelvis radiation, with equivalent tumor control.

Radiation Therapy Physics Quality Assurance and Management Practices in Low- and Middle-Income Countries: An Initial Pilot Survey in Six Countries and Validation Through a Site Visit.

Purpose: Our purpose was to assess physics quality assurance (QA) practices in less resourced radiation therapy (RT) centers to improve quality of care. Methods and Materials: A preliminary study was conducted in 2020 of 13 select RT centers in 6 countries, and in 2021, our team conducted onsite visits to all the RT centers in Ghana, one of the countries from the initial survey. The RT centers included 1 private and 2 public institutions (denoted as Public-1 and Public-2). Follow-up surveys were sent to 17 medical physicists from the site visit. Questions centered on the topics of equipment, institutional practice, physics quality assurance, management, and safety practices. Qualitative and descriptive methods were used for data analysis. Questions regarding operational challenges (machine downtime, patient-related issues, power outages, and staffing) were asked on a 5-point Likert scale. Results: The preliminary survey from 2020 had a 92% response rate. One key result showed that for RT centers in lower gross national income per capita countries there was a direct correlation between QA needs and the gross national income per capita of the country. The needs identified included film/array detectors, independent dose calculation software, calibration of ion chambers, diodes, thermoluminiscence diodes (TLDs), phantoms for verification, Treatment Planning System (TPS) test phantoms, imaging test phantoms and film dosimeters, education, and training. For the post survey after the site visit in 2021, we received a 100% response rate. The private and the Public-1 institutions each have computed tomography simulators located in their RT center. The average daily patient external beam workload for each clinic on a linear accelerator was: private = 25, Public-1 = 55, Public-2 = 40. The Co-60 workload was: Public-1 = 45, Public-2 = 25 (there was no Co-60 at the private hospital). Public-1 and -2 lacked the equipment necessary to conform to best practices in Task Group reports (TG) 142 and 198. Public-2 reported significant operational challenges. Notably, Public-1 and -2 have peer review chart rounds, which are attended by clinical oncologists, medical physicists, physicians, and physics trainees. All 17 physicists who responded to the post site visit survey indicated they had a system of documenting, tracking, and trending patient-related safety incidents, but only 1 physicist reported using International Atomic Energy Agency Safety in Radiation Oncology. Conclusions: The preliminary study showed a direct correlation between QA needs and the development index of a country, and the follow-up survey examines operational and physics QA practices in the RT clinics in Ghana, one of the initial countries surveyed. This will form the basis of a planned continent-wide survey in Africa intended to spotlight QA practices in low- and middle-income countries, the challenges faced, and lessons learned to help understand the gaps and needs to support local physics QA and management programs. Audits during the site visit show education and training remain the most important needs in operating successful QA programs.

E-cigarette use and respiratory symptoms in adults: A systematic review and meta-analysis.

INTRODUCTION: Electronic cigarette (e-cigarette) use is gaining popularity among adults. Monitoring e-cigarette-induced respiratory symptoms is crucial for both clinical and regulatory purposes. We systematically reviewed the current literature to understand the prevalence of respiratory symptoms among exclusive e-cigarette users, dual users, and former smokers. METHODS: Databases searched included PubMed, CINAHL, Cochrane Library, Embase, and Scopus. We included all English-language, empirical quantitative articles that explored the prevalence of e-cigarette-related respiratory symptoms. Random-effects models were utilized in conducting the meta-analyses. The quality of identified studies was evaluated using the NIH Study Quality Assessment Tools. This study is registered with PROSPERO(#CRD42020165973). RESULTS: The literature search identified 1240 references. After removing duplicates and screening for eligibility, 168 studies were included in the final review. The majority of included studies reported a wide range of adverse respiratory symptoms. The respiratory symptoms were prevalent among the exclusive e-cigarette users, dual users, and those who switched from combustible cigarettes to e-cigarettes. Further, out of the RCT studies, 5 were rated as good quality, while 3 were rated as fair. Among the observational studies, 24 were rated as good quality, and 9 were rated as fair. The two experimental studies were both rated as fair quality. CONCLUSIONS: Continued monitoring of respiratory symptoms among e-cigarette users is warranted. Due to the heterogeneity and inconsistencies among studies, which limit result interpretation and highlight the need for studies assessing causal inference, further research using robust study designs is essential. This will provide clinicians with comprehensive knowledge about the potential respiratory risks of e-cigarette use.

A Neptune-mass exoplanet in close orbit around a very low-mass star challenges formation models.

Theories of planet formation predict that low-mass stars should rarely host exoplanets with masses exceeding that of Neptune. We used radial velocity observations to detect a Neptune-mass exoplanet orbiting LHS 3154, a star that is nine times less massive than the Sun. The exoplanet's orbital period is 3.7 days, and its minimum mass is 13.2 Earth masses. We used simulations to show that the high planet-to-star mass ratio (>3.5 × 10-4) is not an expected outcome of either the core accretion or gravitational instability theories of planet formation. In the core-accretion simulations, we show that close-in Neptune-mass planets are only formed if the dust mass of the protoplanetary disk is an order of magnitude greater than typically observed around very low-mass stars.

Dynamics of SARS-CoV-2 Seroprevalence in a Large US population Over a Period of 12 Months.

Due to a combination of asymptomatic or undiagnosed infections, the proportion of the United States population infected with SARS-CoV-2 was unclear from the beginning of the pandemic. We previously established a platform to screen for SARS-CoV-2 positivity across a representative proportion of the US population, from which we reported that almost 17 million Americans were estimated to have had undocumented infections in the Spring of 2020. Since then, vaccine rollout and prevalence of different SARS-CoV-2 variants have further altered seropositivity trends within the United States population. To explore the longitudinal impacts of the pandemic and vaccine responses on seropositivity, we re-enrolled participants from our baseline study in a 6- and 12- month follow-up study to develop a longitudinal antibody profile capable of representing seropositivity within the United States during a critical period just prior to and during the initiation of vaccine rollout. Initial measurements showed that, since July 2020, seropositivity elevated within this population from 4.8% at baseline to 36.2% and 89.3% at 6 and 12 months, respectively. We also evaluated nucleocapsid seropositivity and compared to spike seropositivity to identify trends in infection versus vaccination relative to baseline. These data serve as a window into a critical timeframe within the COVID-19 pandemic response and serve as a resource that could be used in subsequent respiratory illness outbreaks.

Improved safety and quality in intravascular brachytherapy: A multi-institutional study using failure modes and effects analysis.

PURPOSE: Highlight safety considerations in intravascular brachytherapy (IVBT) programs, provide relevant quality assurance (QA) and safety measures, and establish their effectiveness. METHODS AND MATERIALS: Radiation oncologists, medical physicists, and cardiologists from three institutions performed a failure modes and effects analysis (FMEA) on the radiation delivery portion of IVBT. We identified 40 failure modes and rated the severity, occurrence, and detectability before and after consideration of safety practices. Risk priority numbers (RPN) and relative risk rankings were determined, and a sample QA safety checklist was developed. RESULTS: We developed a process map based on multi-institutional consensus. Highest-RPN failure modes were due to incorrect source train length, incorrect vessel diameter, and missing prior radiation history. Based on these, we proposed QA and safety measures: ten of which were not previously recommended. These measures improved occurrence and detectability: reducing the average RPN from 116 to 58 and median from 84 to 40. Importantly, the average RPN of the top 10% of failure modes reduced from 311 to 172. With QA considered, the highest risk failure modes were from contamination and incorrect source train length. CONCLUSIONS: We identified several high-risk failure modes in IVBT procedures and practical safety and QA measures to address them.

Project Inclusive Genetics: Protecting reproductive autonomy from bias via prenatal patient-centered counseling.

Clinician bias negatively impacts the healthcare received by marginalized communities. In this study, we explored factors that influence clinician and trainee bias against individuals with intellectual disabilities and its impact on clinical judgment in prenatal genetic testing settings. Specifically, we examined bias toward a fetus with a higher chance of developing a disability. We compared genetics specialists with their non-expert counterparts. This web-based study included clinical vignettes, implicit association tests (IATs), and an educational module. 595 participants were recruited via their institution or professional society. We conducted statistical analyses, including regression models controlling for key demographic characteristics, to analyze recommendation patterns and degree of change after the module. Genetics expertise strongly correlated with appropriate testing recommendation when the patient would not consider pregnancy termination (r = 1.784 pre-module, r = 1.502 post-module, p < 0.01). Factors that influenced pre-module recommendation to test include increased age (r = -0.029, p < 0.05), high religiosity (r = 0.525, p < 0.05), and participant personal preference against testing (r = 1.112, p < 0.01). Responses among participants without genetics expertise improved after the educational module (Z = -4.435, p < 0.01). 42% of non-experts who answered inappropriately changed their answer to match guidelines after the module. Individual bias, along with structural and institutional bias, permeates family planning encounters and significantly decreases quality of care. We demonstrate here that anti-bias training is effective, particularly for non-expert providers, and it can improve the care provided to individuals with intellectual disability. Evidence-based training such as this one can help providers make appropriate genetic counseling recommendations.

Self-reported COVID-19 infection, and illness severity associated with a large professional-society meeting of the AAPM in 2022.

BACKGROUND: Many in-person conferences were suspended during the initial stages of the COVID-19 pandemic but have recently begun to return to in-person or hybrid formats. However the incidence and severity of COVID-19 infection during conferences, as well as behaviors at meetings associated with infection, are not well known. PURPOSE: We performed a targeted, systematic survey of self-reported COVID-19 infection and severity rates among in-person attendees and potential attendees of a large national medical conference held in hybrid format during the during the Omicron subvariant wave, to provide guidance for future meeting attendees and organizers on COVID-19 risk. METHODS: A survey was sent to all members of the American Association of Physicists in Medicine (AAPM) as well as all attendees of the AAPM 2022 Annual Meeting (held July 10th-14th 2022 in Washington DC) with hybrid format) (total n = 10,627). The survey assessed relevant respondent demographics, views of COVID-19 and in-person meetings, COVID-19 infection during the meeting or the following 7 days, and any COVID-19 treatment received. Descriptive statistics and multivariable logistic regression with odds ratios (OR) and 95% confidence intervals (CI) were used for analysis. RESULTS: The response rate was 13.7% (n = 1464) among the total invitees. Of respondents, 62.9% (n = 921) attended the meeting in person and 37.1% (n = 543) did not. Among in-person meeting attendees, 82.1% (n = 756) attended indoor social events during the meeting including 67.5% (n = 509) who attended a large, AAPM-coordinated social event. Reported COVID-19 infection rates were higher among in-person attendees (15.3%, n = 141) versus those that did not attend in-person (6.1%, n = 33) (p < 0.001). Of those infected, 97.9% (n = 138) recovered entirely at home, with the remaining 2 (1.4%) undergoing emergency room visit without admission, and 1 (unvaccinated) individual (0.7%) reported hospital admission. On multivariable analysis of reported in-person attendee behaviors, only attendance of the large, AAPM-coordinated social event remained significantly associated with COVID-19 infection (OR 2.8, CI 1.8-4.2, p < 0.001). Among in-person attendees, 74.1% (n = 682) agreed that they would feel comfortable attending in-person conferences in the future, 11.8% (n = 109) disagreed, and 14.0% (n = 129) neither agreed nor disagreed. CONCLUSIONS: Despite higher than previously reported COVID-19 infection rates than prior studies, severity of infection was self-limited with no hospitalizations among vaccinated attendees. In-person attendees showed a willingness to return to large-scale indoor social interaction, with a higher rate of COVID-19 infection noted among those who attended a large conference-affiliated social gathering. Most individuals reported feeling comfortable attending other in-person meetings in the future.

Results of a Multi-Disciplinary and Multi-Institutional Pilot Creating High-Yield Physics Educational Content (Hi-Phy).

Purpose: The quality of medical physics education is heterogenous across training programs, despite its importance in radiation oncology (RO) residency training. We present the results of a pilot series of free high-yield physics educational videos covering 4 topics chosen from the American Society for Radiation Oncology core curriculum. Methods and materials: Scripting and storyboarding of videos were iterative processes performed by 2 ROs and 6 medical physicists, with animations created by a university broadcasting specialist. Current RO residents and those who had graduated after 2018 were recruited through social media and e-mail with an aim of 60 participants. Two validated surveys were adapted for use and were completed after each video as well as a final overall assessment. Content was released sequentially after completion of the survey instruments for each prior video. All videos were created and released within 1 year of project initiation with a duration of 9 to 11 minutes. Results: There were 169 enrollees for the pilot from across the world, 211% of the targeted cohort size. Of these, 154 met eligibility criteria and received the first video. One hundred eight enrollees initiated the series and 85 completed the pilot, resulting in a 78% completion rate. Participants reported improved understanding and confidence applying the knowledge learned in the videos (median score 4 out of 5). All participants reported that the use of graphic animation improved understanding across all videos. Ninety-three percent agreed with a need for additional resources geared specifically toward RO residents and 100% would recommend these videos to other residents. Use metrics revealed the average watch time was 7 minutes (range, 6:17-7:15). Conclusions: The high-yield educational physics video pilot series was successful in developing videos that were effective in teaching RO physics concepts.

A deep-learning-based dose verification tool utilizing fluence maps for a cobalt-60 compensator-based intensity-modulated radiation therapy system.

Background and purpose: A novel cobalt-60 compensator-based intensity-modulated radiation therapy (IMRT) system was developed for a resource-limited environment but lacked an efficient dose verification algorithm. The aim of this study was to develop a deep-learning-based dose verification algorithm for accurate and rapid dose predictions. Materials and methods: A deep-learning network was employed to predict the doses from static fields related to beam commissioning. Inputs were a cube-shaped phantom, a beam binary mask, and an intersecting volume of the phantom and beam binary mask, while output was a 3-dimensional (3D) dose. The same network was extended to predict patient-specific doses for head and neck cancers using two different approaches. A field-based method predicted doses for each field and combined all calculated doses into a plan, while the plan-based method combined all nine fluences into a plan to predict doses. Inputs included patient computed tomography (CT) scans, binary beam masks, and fluence maps truncated to the patient's CT in 3D. Results: For static fields, predictions agreed well with ground truths with average deviations of less than 0.5% for percent depth doses and profiles. Even though the field-based method showed excellent prediction performance for each field, the plan-based method showed better agreement between clinical and predicted dose distributions. The distributed dose deviations for all planned target volumes and organs at risk were within 1.3 Gy. The calculation speed for each case was within two seconds. Conclusions: A deep-learning-based dose verification tool can accurately and rapidly predict doses for a novel cobalt-60 compensator-based IMRT system.

Lessons Learned From an Educational Pilot: High-Yield Physics Videos for Radiation Oncology Residents.

Radiation oncology is uniquely poised to benefit from the development of remote learning tools, given the need for mastery of often challenging basic science topics, as well as the interprogram heterogeneity of resident educational quality. Our team successfully created and disseminated 4 high-yield animated physics educational videos through the collaboration of radiation oncologists, medical physicists, and a graphic design specialist. This is a unique process requiring significant intellectual, monetary, and time capital. In this article, we describe important lessons learned throughout this process, in hopes that others will learn from our experience, applying the following concepts to their own digital content creation. These lessons include (1) playing to your teammates' strengths and personalizing tasks, rather than equally dividing work; (2) anticipating animations before and during script writing; (3) developing multiple routes of communication and being open to which one works best for your team; and (4) discussing funding up front and collaborating within an affiliated institution or company for graphic design to alleviate the financial stress of such endeavors.

Commissioning and dosimetric validation of a novel compensator-based Co-60 IMRT system for evaluating suitability to automated treatment planning.

PURPOSE: A novel compensator-based system has been proposed which delivers intensity-modulated radiation therapy (IMRT) with cobalt-60 beams. This could improve access to advanced radiotherapy in low- and middle-income countries. For this system to be clinically viable and to be adapted into the Radiation Planning Assistant (RPA), being developed to offer automated planning services in low- and middle-income countries, it is necessary to commission and validate it in a commercial treatment planning system (TPS). METHODS: The novel treatment device considered here employs a cobalt-60 source and nine compensators. Each compensator is produced by 3-D printing a thin plastic mold which is then filled on-demand within the machine with reusable 2-mm-diameter spherical tungsten balls. This system was commissioned in the Eclipse TPS and validation tests were conducted with Monte Carlo using Geant4 Application for Tomographic Emission for percentage depth dose, in-plane profiles, penumbra, and IMRT dose validation. And the American Association of Physicists in Medicine Task Group 119 benchmarking testing was performed. Additionally, compensator-based cobalt-60 IMRT plans were created for 46 head-and-neck cancer cases and compared to the linac-based volumetric modulated arc therapy (VMAT) plans used clinically, then dosimetric parameters were evaluated. Beam-on time for each field was calculated. In addition, the measurement was also performed in a limited environment and compared with the Monte Carlo simulations. RESULTS: The differences in percent depth doses and in-plane profiles between the Eclipse and Monte Carlo simulations were 0.65% ± 0.41% and 1.02% ± 0.99%, respectively, and the 80%-20% penumbra agreed within 0.46 ± 0.27 mm. For the Task Group 119 validation plans, all treatment planning goals were met and gamma passing rates were >95% (3%/3 mm criteria). In 46 clinical head-and-neck cases, the cobalt-60 compensator-based IMRT plans had planning target volume (PTV) coverages similar to linac-based VMAT plans: all dosimetric values for PTV were within 1.5%. The organs at risk dose parameters were somewhat higher in cobalt-60 compensator-based IMRT plans versus linac-based VMAT plans. The mean dose differences for the spinal cord, brain, and brainstem were 4.43 ± 1.92, 3.39 ± 4.67, and 2.40 ± 3.71 Gy, while those for the rest of the organs were <1 Gy. The average beam-on time per field was 0.42 ± 0.10 min for the 6 MV multi-leaf-collimator plans while those for the cobalt-60 compensator plans were 0.17 ± 0.01 and 0.31 ± 0.01 min at the dose rates of 350 and 175 cGy/min. There was a good agreement between in-plane profiles from measurements and Monte Carlo simulations, which differences are 1.34 ± 1.90% and 0.13 ± 2.16% for two different fields. CONCLUSIONS: A novel compensator-based IMRT system using cobalt-60 beams was commissioned and validated in a commercial TPS. Plan quality with this system was comparable to that of linac-based plans in all test cases with shorter estimated beam-on times. This system enables reliable, high-quality plans with reduced cost and complexity and may have benefits for underserved regions of the world. This system is being integrated into the RPA, a web-based platform for auto-contouring and auto-planning.