The dosimetric accuracy of a commercial model-based dose calculation algorithm in modeling a six-groove direction modulated brachytherapy tandem applicator.

OBJECTIVE: With advancements in high-dose rate brachytherapy, the clinical translation of intensity modulated brachytherapy (IMBT) innovations necessitates utilization of model-based dose calculation algorithms (MBDCA) for accurate and rapid dose calculations. This study uniquely benchmarks a commercial MBDCA, BrachyVision ACUROSTM (BVA), against Monte Carlo (MI) simulations, evaluating dose distributions for a novel IMBT applicator, termed as the six-groove Direction Modulated Brachytherapy (DMBT) tandem, expanding beyond previous focus on partially shielded vaginal cylinder applicators, through a novel methodology. Approach: The DMBT tandem applicator, made of a tungsten alloy with six evenly spaced grooves, was simulated using the GEANT4 MC code. Subsequently, two main scenarios were created using the BVA and reproduced by the MC simulations: "Source at the Center of the Water Phantom (SACWP)" and "Source at the Middle of the Applicator (SAMA)" for three cubical virtual water phantoms (20 cm)3, (30 cm)3, and (40 cm)3. A track length estimator was utilized for dose calculation and 2D/3D scoring were performed. The difference in isodose surfaces/lines (i.e., coverage) at each voxel, ∆DIsodose Levels/Lines, was thus calculated for relevant normalization points (rref). Results: The coverage was comparable, based on 2D scoring, between the BVA and MC isodose surfaces/lines for the region of clinical relevance, (i.e., within 5 cm radius from the source) with ∆DIsodose Lines (rref: 1 cm from the source) falling within 2% for the two scenarios for all phantom sizes. For the phantom (20 cm)3, ∆DIsodose Level (3D scoring) recorded the range [-3.0% +6.5%] ([-7.4% +7.3%]) for 95% of the voxels of the same scoring volume for the SACWP (SAMA) scenario. Significance: The results indicated that the BVA could render comparable coverage as compared to the MC simulations in the region of clinical relevance for different phantom sizes. ∆DIsodose Lines may offer an advantageous metric for evaluation of MBDCAs in clinical setting. .

Home- vs Office-Based Narrowband UV-B Phototherapy for Patients With Psoriasis: The LITE Randomized Clinical Trial.

Importance: Office-based phototherapy is cost-effective for psoriasis but difficult to access. Home-based phototherapy is patient preferred but has limited clinical data, particularly in patients with darker skin. Objective: To compare the effectiveness of home- vs office-based narrowband UV-B phototherapy for psoriasis. Design, Setting, and Participants: The Light Treatment Effectiveness study was an investigator-initiated, pragmatic, open-label, parallel-group, multicenter, noninferiority randomized clinical trial embedded in routine care at 42 academic and private clinical dermatology practices in the US. Enrollment occurred from March 1, 2019, to December 4, 2023, with follow-up through June 2024. Participants were 12 years and older with plaque or guttate psoriasis who were candidates for home- and office-based phototherapy. Interventions: Participants were randomized to receive a home narrowband UV-B machine with guided mode dosimetry or routine care with office-based narrowband UV-B for 12 weeks, followed by an additional 12-week observation period. Main Outcomes and Measures: The coprimary effectiveness outcomes were Physician Global Assessment (PGA) dichotomized as clear/almost clear skin (score of ≤1) at the end of the intervention period and Dermatology Life Quality Index (DLQI) score of 5 or lower (no to small effect on quality of life) at week 12. Results: Of 783 patients enrolled (mean [SD] age, 48.0 [15.5] years; 376 [48.0%] female), 393 received home-based phototherapy and 390 received office-based phototherapy, with 350 (44.7%) having skin phototype (SPT) I/II, 350 (44.7%) having SPT III/IV, and 83 (10.6%) having SPT V/VI. A total of 93 patients (11.9%) were receiving systemic treatment. At baseline, mean (SD) PGA was 2.7 (0.8) and DLQI was 12.2 (7.2). At week 12, 129 patients (32.8%) receiving home-based phototherapy and 100 patients (25.6%) receiving office-based phototherapy achieved clear/almost clear skin, and 206 (52.4%) and 131 (33.6%) achieved DLQI of 5 or lower, respectively. Home-based phototherapy was noninferior to office-based phototherapy for PGA and DLQI in the overall population and across all SPTs. Home-based phototherapy, compared to office-based phototherapy, was associated with better treatment adherence (202 patients [51.4%] vs 62 patients [15.9%]; P < .001), lower burden of indirect costs to patients, and more episodes of persistent erythema (466 of 7957 treatments [5.9%] vs 46 of 3934 treatments [1.2%]; P < .001). Both treatments were well tolerated with no discontinuations due to adverse events. Conclusions and Relevance: In this randomized clinical trial, home-based phototherapy was as effective as office-based phototherapy for plaque or guttate psoriasis in everyday clinical practice and had less burden to patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03726489.

Attention 3D U-NET for dose distribution prediction of high-dose-rate brachytherapy of cervical cancer: Direction modulated brachytherapy tandem applicator.

BACKGROUND: Direction Modulated Brachytherapy (DMBT) enables conformal dose distributions. However, clinicians may face challenges in creating viable treatment plans within a fast-paced clinical setting, especially for a novel technology like DMBT, where cumulative clinical experience is limited. Deep learning-based dose prediction methods have emerged as effective tools for enhancing efficiency. PURPOSE: To develop a voxel-wise dose prediction model using an attention-gating mechanism and a 3D UNET for cervical cancer high-dose-rate (HDR) brachytherapy treatment planning with DMBT six-groove tandems with ovoids or ring applicators. METHODS: A multi-institutional cohort of 122 retrospective clinical HDR brachytherapy plans treated to a prescription dose in the range of 4.8-7.0 Gy/fraction was used. A DMBT tandem model was constructed and incorporated onto a research version of BrachyVision Treatment Planning System (BV-TPS) as a 3D solid model applicator and retrospectively re-planned all cases by seasoned experts. Those plans were randomly divided into 64:16:20 as training, validating, and testing cohorts, respectively. Data augmentation was applied to the training and validation sets to increase the size by a factor of 4. An attention-gated 3D UNET architecture model was developed to predict full 3D dose distributions based on high-risk clinical target volume (CTVHR) and organs at risk (OARs) contour information. The model was trained using the mean absolute error loss function, Adam optimization algorithm, a learning rate of 0.001, 250 epochs, and a batch size of eight. In addition, a baseline UNET model was trained similarly for comparison. The model performance was evaluated on the testing dataset by analyzing the outcomes in terms of mean dose values and derived dose-volume-histogram indices from 3D dose distributions and comparing the generated dose distributions against the ground-truth dose distributions using dose statistics and clinically meaningful dosimetric indices. RESULTS: The proposed attention-gated 3D UNET model showed competitive accuracy in predicting 3D dose distributions that closely resemble the ground-truth dose distributions. The average values of the mean absolute errors were 1.82 ± 29.09 Gy (vs. 6.41 ± 20.16 Gy for a baseline UNET) in CTVHR, 0.89 ± 1.25 Gy (vs. 0.94 ± 3.96 Gy for a baseline UNET) in the bladder, 0.33 ± 0.67 Gy (vs. 0.53 ± 1.66 Gy for a baseline UNET) in the rectum, and 0.55 ± 1.57 Gy (vs. 0.76 ± 2.89 Gy for a baseline UNET) in the sigmoid. The results showed that the mean absolute error (MAE) for the bladder, rectum, and sigmoid were 0.22 ± 1.22 Gy (3.62%) (p = 0.015), 0.21 ± 1.06 Gy (2.20%) (p = 0.172), and -0.03 ± 0.54 Gy (1.13%) (p = 0.774), respectively. The MAE for D90, V100%, and V150% of the CTVHR were 0.46 ± 2.44 Gy (8.14%) (p = 0.018), 0.57 ± 11.25% (5.23%) (p = 0.283), and -0.43 ± 19.36% (4.62%) (p = 0.190), respectively. The proposed model needs less than 5 s to predict a full 3D dose distribution of 64 × 64 × 64 voxels for any new patient plan, thus making it sufficient for near real-time applications and aiding with decision-making in the clinic. CONCLUSIONS: Attention gated 3D-UNET model demonstrated a capability in predicting voxel-wise dose prediction, in comparison to 3D UNET, for DMBT intracavitary brachytherapy planning. The proposed model could be used to obtain dose distributions for near real-time decision-making before DMBT planning and quality assurance. This will guide future automated planning, making the workflow more efficient and clinically viable.

Optimization of treatment workflow for 0.35T MR-Linac system.

PURPOSE: This study presents a novel and comprehensive framework for evaluating magnetic resonance guided radiotherapy (MRgRT) workflow by integrating the Failure Modes and Effects Analysis (FMEA) approach with Time-Driven Activity-Based Costing (TDABC). We assess the workflow for safety, quality, and economic implications, providing a holistic understanding of the MRgRT implementation. The aim is to offer valuable insights to healthcare practitioners and administrators, facilitating informed decision-making regarding the 0.35T MRIdian MR-Linac system's clinical workflow. METHODS: For FMEA, a multidisciplinary team followed the TG-100 methodology to assess the MRgRT workflow's potential failure modes. Following the mitigation of primary failure modes and workflow optimization, a treatment process was established for TDABC analysis. The TDABC was applied to both MRgRT and computed tomography guided RT (CTgRT) for typical five-fraction stereotactic body RT (SBRT) treatments, assessing total workflow and costs associated between the two treatment workflows. RESULTS: A total of 279 failure modes were identified, with 31 categorized as high-risk, 55 as medium-risk, and the rest as low-risk. The top 20% risk priority numbers (RPN) were determined for each radiation oncology care team member. Total MRgRT and CTgRT costs were assessed. Implementing technological advancements, such as real-time multi leaf collimator (MLC) tracking with volumetric modulated arc therapy (VMAT), auto-segmentation, and increasing the Linac dose rate, led to significant cost savings for MRgRT. CONCLUSION: In this study, we integrated FMEA with TDABC to comprehensively evaluate the workflow and the associated costs of MRgRT compared to conventional CTgRT for five-fraction SBRT treatments. FMEA analysis identified critical failure modes, offering insights to enhance patient safety. TDABC analysis revealed that while MRgRT provides unique advantages, it may involve higher costs. Our findings underscore the importance of exploring cost-effective strategies and key technological advancements to ensure the widespread adoption and financial sustainability of MRgRT in clinical practice.

Using Guidelines of Care to Lower Cardiovascular Risk in Patients with Psoriasis.

National guidelines define psoriasis as a risk enhancer for cardiovascular disease and recommend increased monitoring and more intense management of cardiovascular risk factors in these patients, who face an increased burden of cardiovascular disease morbidity and mortality. Screening for modifiable cardiovascular risk factors, including blood pressure, weight, cholesterol, glucose, and smoking, can be efficiently incorporated into routine dermatology clinical practice. Partnerships with primary care providers and preventive cardiologists are essential to improving management of cardiovascular risk in patients with psoriasis.

The effect of vaginal cylinder inhomogeneity on the HDR brachytherapy dose calculations using Monte Carlo simulations.

PURPOSE: To analytically assess the heterogeneity effect of vaginal cylinders (VC) made of high-density plastics on dose calculations, considering the prescription point (surface or 5 mm beyond the surface), and benchmark the accuracy of a commercial model-based dose calculation (MBDC) algorithm using Monte Carlo (MC) simulations. METHODS AND MATERIALS: The GEANT4 MC code was used to simulate a commercial 192 Ir HDR source and VC, with diameters ranging from 20 to 35 mm, inside a virtual water phantom. Standard plans were generated from a commercial treatment planning system [TPS-BrachyVision ACUROS (BV)] optimized for a treatment length of 5 cm through two dose calculation approaches: (1) assuming all the environment as water (i.e., Dw,w-MC & Dw,w-TG43 ) and (2) accounting for the heterogeneity of VC applicators (i.e., Dw,w-App-MC & Dw,w-App-MBDC ). The compared isodose lines, and dose & energy difference maps were extracted for analysis. In addition, the dose difference on the peripheral surface, along the applicator and at middle of treatment length, as well as apical tip was evaluated. RESULTS: The Dw,w-App-MC results indicated that the VC heterogeneity can cause a dose reduction of (up to) % 6.8 on average (for all sizes) on the peripheral surface, translating to 1 mm shrinkage of the isodose lines compared to Dw,w-MC . In addition, the results denoted that BV overestimates the dose on the peripheral surface and apical tip of about 3.7% and 17.9%, respectively, (i.e., Dw,w-App-MBDC vs Dw,w-App-MC ) when prescribing to the surface. However, the difference between the two were negligible at the prescription point when prescribing to 5 mm beyond the surface. CONCLUSION: The VCs' heterogeneity could cause dose reduction when prescribing dose to the surface of the applicator, and hence increases the level of uncertainty. Thus, reviewing the TG43 results, in addition to ACUROS, becomes prudent, when evaluating the surface coverage at the apex.

A novel direction modulated brachytherapy technique for urethra sparing in high-dose-rate brachytherapy of prostate cancer.

PURPOSE: Image-guided high-dose-rate (HDR) prostate brachytherapy is a safe and effective treatment option for prostate cancer patients; however, some patients still experience acute and late genitourinary (GU) toxicity. Studies have shown that urethral dose is associated with the incidence and severity of GU toxicity. Therefore, a technique that can further spare the urethra while ensuring adequate target coverage is highly desirable. Intensity modulated brachytherapy (IMBT) designs, such as rotating shield brachytherapy (RSBT), offer ideal dosimetry theoretically but are challenging to implement clinically due to the need for high precision in moving the treatment delivery mechanisms synchronized with the source loading. In this study, we propose a novel relatively easy-to-implement solution based on the direction modulated brachytherapy (DMBT) design concept, which does not involve moving parts and works effectively with the ubiquitous 192Ir source. MATERIALS AND METHODS: The popular Varian VS2000 (VS) and GammaMedPlus (GMP) 192Ir sources, with outer diameters of 0.6 mm and 0.9 mm, respectively, were simulated using the GEANT4 Monte Carlo (MC) simulation code. The novel DMBT needle concept consists of a 14-gauge nitinol needle, which houses a platinum shield inside. A single groove, consistent with the outer diameter of each source, was incorporated inside the platinum shield to accommodate the HDR source. The maximum thickness of the shield was 1.1 mm (0.8 mm) for the VS (GMP) source. To evaluate the effectiveness of the DMBT needle concept in reducing urethral dose, 6 patient cases were studied and DMBT plans were created by replacing two needles close to the urethra with the DMBT needles. The dosimetric comparisons between the DMBT and reference clinical plans were done by assessing the dose-volume histogram (DVH) planning criteria for the target coverage and organs-at-risk. RESULTS: The MC results showed that the use of the novel DMBT needle design with the VS source (GMP source) could reduce the dose by 49.6% (39.2%) at 1 cm from the needle behind the platinum shield, as compared to the unshielded side. Additionally, when using the same DVH planning criteria as the original plan, the DMBT plan with the VS (GMP) source reduced the maximum urethral dose by 10.3% ± 5.6% (8.1% ± 5.0%) and 17.7% ± 14.2% (16.6% ± 13.3%) for 0 mm and 2 mm margins, respectively, while maintaining equivalent V90% and D100 target coverage. CONCLUSION: The novel DMBT technique offers a promising clinically implementable solution for sparing urethra, particularly in pre-apical region, without compromising the target coverage or increasing treatment time.

The role of 18F-FDG PET/CT in primary cutaneous lymphoma: an educational review.

INTRODUCTION: Primary cutaneous lymphoma (PCL) is a cutaneous non-Hodgkin's lymphoma that originates in the skin and lacks extracutaneous spread upon initial diagnosis. The clinical management of secondary cutaneous lymphomas is different from that of PCLs, and earlier detection is associated with better prognosis. Accurate staging is necessary to determine the extent of disease and to choose the appropriate treatment. The aim of this review is to investigate the current and potential roles of 18F- fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in the diagnosis, staging, and monitoring of PCLs. METHODS: A focused review of the scientific literature was performed using inclusion criteria to filter results pertaining to human clinical studies performed between 2015 and 2021 that analyzed cutaneous PCL lesions on 18F PET/CT imaging. RESULTS & CONCLUSION: A review of 9 clinical studies published after 2015 concluded that 18F-FDG PET/CT is highly sensitive and specific for aggressive PCLs and proved valuable for identifying extracutaneous disease. These studies found 18F-FDG PET/CT highly useful for guiding lymph node biopsy and that imaging results influenced therapeutic decision in many cases. These studies also predominantly concluded that 18F-FDG PET/CT is more sensitive than computed tomography (CT) alone for detection of subcutaneous PCL lesions. Routine revision of nonattenuation-corrected (NAC) PET images may improve the sensitivity of 18F-FDG PET/CT for detection of indolent cutaneous lesions and may expand the potential uses of 18F-FDG PET/CT in the clinic. Furthermore, calculating a global disease score from 18F-FDG PET/CT at every follow-up visit may simplify assessment of disease progression in the early clinical stages, as well as predict the prognosis of disease in patients with PCL.

Efficient Targeted Delivery of Bifunctional Circular Aptamer-ASO Chimera to Suppress the SARS-CoV-2 Proliferation and Inflammation.

Inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and excessive inflammation is the current task in the prevention and treatment of corona vireus disease 2019 (COVID-19). Here, a dual-function circular aptamer-ASO chimera (circSApt-NASO) is designed to suppress SARS-CoV-2 replication and inflammation. The chemically unmodified circSApt-NASO exhibits high serum stability by artificial cyclization. It is also demonstrated that the SApt binding to spike protein enables the chimera to be efficiently delivered into the host cells expressing ACE2 along with the infection of SARS-CoV-2. Among them, the SApt potently inhibits spike-induced inflammation. The NASO targeting to silence N genes not only display robust anti-N-induced inflammatory activity, but also achieve efficient inhibition of SARS-CoV-2 replication. Overall, benefiting from the high stability of the cyclization, antispike aptamer-dependent, and viral infection-mediate targeted delivery, the circSApt-NASO displays robust potential against authentic SARS-CoV-2 and Omicron, providing a promising specific anti-inflammatory and antiproliferative reagent for therapeutic COVID-19.

A Novel Workflow with a Customizable 3D Printed Vaginal Template and a Direction Modulated Brachytherapy (DMBT) Tandem Applicator for Adaptive Interstitial Brachytherapy of the Cervix.

A novel clinical workflow utilizing a direction modulated brachytherapy (DMBT) tandem applicator in combination with a patient-specific, 3D printed vaginal needle-track template for an advanced image-guided adaptive interstitial brachytherapy of the cervix. The proposed workflow has three main steps: (1) pre-treatment MRI, (2) an initial optimization of the needle positions based on the DMBT tandem positioning and patient anatomy, and a subsequent inverse optimization using the combined DMBT tandem and needles, and (3) rapid 3D printing. We retrospectively re-planned five patient cases for two scenarios; one plan with the DMBT tandem (T) and ovoids (O) with the original needle (ND) positions (DMBT + O + ND) and another with the DMBT T&O and spatially reoptimized needles (OptN) positions (DMBT + O + OptN). All retrospectively reoptimized plans have been compared to the original plan (OP) as well. The accuracy of 3D printing was verified through the image registration between the planning CT and the CT of the 3D-printed template. The average difference in D2cc for the bladder, rectum, and sigmoid between the OPs and DMBT + O + OptNs were -8.03 ± 4.04%, -18.67 ± 5.07%, and -26.53 ± 4.85%, respectively. In addition, these average differences between the DMBT + O + ND and DMBT + O + OptNs were -2.55 ± 1.87%, -10.70 ± 3.45%, and -22.03 ± 6.01%, respectively. The benefits could be significant for the patients in terms of target coverage and normal tissue sparing and increase the optimality over free-hand needle positioning.

Representation of Asian American Populations in Medical School Curricula.

Importance: Despite being one of the fastest-growing populations in the US, the Asian American population is often misrepresented in and omitted from health research and policy debate. There is a current lack of understanding of how Asian American populations are portrayed in medical school curricula. Objective: To assess how Asian American populations and their subgroups are represented in medical school curricula. Design, Setting, and Participants: In this qualitative study, the content of 632 lectures from all 19 courses of the preclinical curriculum at a single US institution from the academic year 2020 to 2021 was analyzed to identify and characterize unique mentions of race and ethnicity as well as granular ethnicity. Among the 632 lectures, we identified 256 nonrepetitive, unique mentions of race and ethnicity or granular ethnicity. These unique mentions were coded and analyzed for emerging patterns of use. Main Outcomes and Measures: Study outcomes included (1) the frequency of specific racial and ethnic categories mentioned in the curriculum, (2) the relative proportion of mentions of race and ethnicity that involved or included Asian American data by courses and context, and (3) key themes representing emerging patterns found from qualitative analysis of curriculum content for mentions of Asian American populations or lack thereof. Results: Among the 632 lectures, 256 nonrepetitive mentions of race and ethnicity or granular ethnicity were identified; of these, Asian American populations and/or their subgroups were mentioned in 79 of the instances (30.9%). The most common terms used to denote Asian American populations were Asian, with 36 mentions (45.6%); followed by Japanese, with 10 mentions (12.7%); and Chinese, with 8 mentions (10.1%). Overall, there were 26 mentions (10.2%) of American Indian or Alaska Native populations, 12 mentions (4.7%) of Asian and Pacific Islander or Asian American and Pacific Islander populations, 67 mentions (26.2%) of Asian or Asian American populations, 143 mentions (55.9%) of Black or African American populations, 62 mentions (24.2%) of Hispanic or Latino populations, 4 mentions (1.6%) of Native Hawaiian or Pacific Islander populations, and 154 mentions (60.2%) of White populations. During the analysis of the curriculum for representation of Asian American populations, the following 5 key themes emerged from the data: (1) omission, (2) aggregation, (3) inconsistent categorization, (4) misidentification of granular ethnicity, and (5) association of race and ethnicity with disease. Conclusions and Relevance: This qualitative study suggests that the curriculum from a single US medical school largely mirrors the inappropriate use of race and ethnicity found in published health literature and clinical guidelines. Solutions with long-term results will require collaboration among diverse groups of interest to adopt inclusive research programs and design. Such solutions could better equip students in combating race-based medicine and could promote community outreach programs built based on trust.

AAPM task group report 303 endorsed by the ABS: MRI implementation in HDR brachytherapy-Considerations from simulation to treatment.

The task group (TG) on magnetic resonance imaging (MRI) implementation in high-dose-rate (HDR) brachytherapy (BT)-Considerations from simulation to treatment, TG 303, was constituted by the American Association of Physicists in Medicine's (AAPM's) Science Council under the direction of the Therapy Physics Committee, the Brachytherapy Subcommittee, and the Working Group on Brachytherapy Clinical Applications. The TG was charged with developing recommendations for commissioning, clinical implementation, and on-going quality assurance (QA). Additionally, the TG was charged with describing HDR BT workflows and evaluating practical consideration that arise when implementing MR imaging. For brevity, the report is focused on the treatment of gynecologic and prostate cancer. The TG report provides an introduction and rationale for MRI implementation in BT, a review of previous publications on topics including available applicators, clinical trials, previously published BT-related TG reports, and new image-guided recommendations beyond CT-based practices. The report describes MRI protocols and methodologies, including recommendations for the clinical implementation and logical considerations for MR imaging for HDR BT. Given the evolution from prescriptive to risk-based QA, an example of a risk-based analysis using MRI-based, prostate HDR BT is presented. In summary, the TG report is intended to provide clear and comprehensive guidelines and recommendations for commissioning, clinical implementation, and QA for MRI-based HDR BT that may be utilized by the medical physics community to streamline this process. This report is endorsed by the American Brachytherapy Society.

Investigation of Isotoxic Dose Escalation and Plan Quality with TDABC Analysis on a 0.35 T MR-Linac (MRL) System in Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided Radiation Therapy (MRgRT) for Primary Pancreatic Cancer.

This study investigates plan quality generated by an MR-Linac (MRL) treatment planning system (TPS) for 5-fraction stereotactic body radiation therapy (SBRT) of primary pancreatic cancer (PCa). In addition, an isotoxic dose escalation was investigated with the MRL TPS based on stereotactic MR-guided adaptive radiation therapy (SMART) trial constraints. A clinical workflow was developed for adaptive and non-adaptive treatments with the MRL, on which a time-driven activity-based costing (TDABC) analysis was performed to quantify clinical efficacy. Fifteen PCa patients previously treated with a conventional Linac were retrospectively re-planned for this study. Three plans were generated for each patient using the original prescription dose (PD) and organ at risk (OAR) constraints (Plan 1), following SMART trial's OAR constraints but with the original PD (Plan 2), starting with Plan 2, following an isotoxic dose escalation strategy where the dose was escalated until any one of the SMART trial's OAR constraints reached its limit (Plan 3). Conformity index (CI) and the ratio of the 50% isodose volume to PTV (R50%) conformity metrics were calculated for all 45 MRL plans, in addition to standard dose-volume indices. Forty-five MRL plans were created which met their respective dosimetric criteria described above. For Plan 1, the MRL TPS successfully achieved equivalent or lower OAR doses while maintaining the prescribed PTV coverage for the 15 plans. A maximum dose to the small bowel was reduced on average by 4.97 Gy (range: 1.11-10.58 Gy). For Plan 2, the MRL TPS successfully met all SMART trial OAR constraints while maintaining equivalent PTV coverage. For Plan 3, the MRL TPS was able to escalate the prescription dose from the original 25-33 Gy by, on average, 36 Gy (range: 15-70 Gy), and dose to the PTV was successfully escalated to at least 50 Gy for all 15 plans. These achievements were made possible, in part, due to the omission of the ITV afforded by the MRL's real-time target tracking technology and sharper dose penumbra due to its unique dual-focus MLC design. The 0.35T MRL TPS can generate plans that are equivalent to conventional Linac-based plans for SBRT of PCa. Through analyzing Plan 2 and 3 strategies, and due to the real-time target localization capabilities of the MRL system, increased OAR sparing and/or target dose escalation are possible.

The design of a novel direction modulated brachytherapy vaginal cylinder applicator for optimizing coverage of the apex.

PURPOSE: High-dose-rate (HDR) vaginal cuff brachytherapy is an effective adjuvant therapy for women with stage I endometrial cancer. Although infrequent, failures do occur, most frequently at the vaginal vault. A potential cause of failure is insufficient dosimetric coverage at the vaginal apex due to cold spots from the anisotropic dose distribution of the source. Here, we propose a novel direction modulated brachytherapy (DMBT)-concept vaginal cylinder (VC) applicator that resolves this dosimetric issue. METHODS AND MATERIALS: The novel DMBT-VC applicator was designed and simulated with the GEANT4 Monte Carlo code. The outer cylinder material chosen was polyphenylsulfone (PPSU) plastic, and the central part was a detachable rod, housing a single lumen made of either polyether ether ketone (PEEK) plastic or an MR-compatible tungsten alloy. The PPSU-based outer cylinder, together with the inner PEEK rod provides the dose distribution of a conventional VC applicator. The PEEK rod is then replaced with an MR-compatible tungsten alloy rod of the same dimensions to generate directional "pencil-like" beams to compensate for the anisotropic cold spots. Two widely used 192 Ir HDR sources, VS2000 and GammaMedPlus, were also simulated. RESULTS: The novel DMBT-VC applicator was able to remove the underdosage at the apex due to the anisotropy effect regardless of the HDR sources without unnecessarily increasing the dose to the periphery of the applicator. Also, further directional modulation to reach deeper in the apex by up to 14 mm beyond the VC surface was achievable, again without increasing the peripheral doses. Total treatment dwell times increased only by 7-13%. CONCLUSIONS: The novel DMBT-VC applicator provides improved dose coverage at the vaginal apex by overcoming the classical anisotropy issue ubiquitous to all HDR brachytherapy sources. The next step in development of the device is manufacturing a prototype for clinical testing.

Emerging technologies in brachytherapy.

Brachytherapy is a mature treatment modality. The literature is abundant in terms of review articles and comprehensive books on the latest established as well as evolving clinical practices. The intent of this article is to part ways and look beyond the current state-of-the-art and review emerging technologies that are noteworthy and perhaps may drive the future innovations in the field. There are plenty of candidate topics that deserve a deeper look, of course, but with practical limits in this communicative platform, we explore four topics that perhaps is worthwhile to review in detail at this time. First, intensity modulated brachytherapy (IMBT) is reviewed. The IMBT takes advantage ofanisotropicradiation profile generated through intelligent high-density shielding designs incorporated onto sources and applicators such to achieve high quality plans. Second, emerging applications of 3D printing (i.e. additive manufacturing) in brachytherapy are reviewed. With the advent of 3D printing, interest in this technology in brachytherapy has been immense and translation swift due to their potential to tailor applicators and treatments customizable to each individual patient. This is followed by, in third, innovations in treatment planning concerning catheter placement and dwell times where new modelling approaches, solution algorithms, and technological advances are reviewed. And, fourth and lastly, applications of a new machine learning technique, called deep learning, which has the potential to improve and automate all aspects of brachytherapy workflow, are reviewed. We do not expect that all ideas and innovations reviewed in this article will ultimately reach clinic but, nonetheless, this review provides a decent glimpse of what is to come. It would be exciting to monitor as IMBT, 3D printing, novel optimization algorithms, and deep learning technologies evolve over time and translate into pilot testing and sensibly phased clinical trials, and ultimately make a difference for cancer patients. Today's fancy is tomorrow's reality. The future is bright for brachytherapy.

A Comparative Study of Common Nature-Inspired Algorithms for Continuous Function Optimization.

Over previous decades, many nature-inspired optimization algorithms (NIOAs) have been proposed and applied due to their importance and significance. Some survey studies have also been made to investigate NIOAs and their variants and applications. However, these comparative studies mainly focus on one single NIOA, and there lacks a comprehensive comparative and contrastive study of the existing NIOAs. To fill this gap, we spent a great effort to conduct this comprehensive survey. In this survey, more than 120 meta-heuristic algorithms have been collected and, among them, the most popular and common 11 NIOAs are selected. Their accuracy, stability, efficiency and parameter sensitivity are evaluated based on the 30 black-box optimization benchmarking (BBOB) functions. Furthermore, we apply the Friedman test and Nemenyi test to analyze the performance of the compared NIOAs. In this survey, we provide a unified formal description of the 11 NIOAs in order to compare their similarities and differences in depth and a systematic summarization of the challenging problems and research directions for the whole NIOAs field. This comparative study attempts to provide a broader perspective and meaningful enlightenment to understand NIOAs.

Strategies for research participant engagement: A synthetic review and conceptual framework.

BACKGROUND: Research participant engagement, which we define as recruitment and retention in clinical trials, is a costly and challenging issue in clinical research. Research teams have leveraged a variety of strategies to increase research participant engagement in clinical trials, although a framework and evidence for effective participant engagement strategies are lacking. We (1) developed a novel conceptual framework for strategies used to recruit and retain participants in clinical trials based on their underlying behavioral principles and (2) categorized empirically tested recruitment and retention strategies in this novel framework. METHODS: We conducted a synthetic analysis of interventions tested in studies from two Cochrane reviews on clinical trial recruitment and retention, which included studies from 1986 to 2015. We developed a conceptual framework of behavioral strategies for increasing research participant engagement using deductive and inductive approaches with the studies included in the Cochrane reviews. Reviewed interventions were then categorized using this framework. We examined the results of reviewed interventions and categorized the effects on clinical trial recruitment and retention as significantly positive, null, or significantly negative; summary statistics are presented for the frequency and effects of each behavioral strategy type. RESULTS: We analyzed 141 unique interventions across 96 studies: 91 interventions targeted clinical trial research participant recruitment and 50 targeted retention. Our framework included 14 behavioral strategies to improve research participant engagement grouped into four general approaches: changing attitudes by appealing to social motivators, changing attitudes by targeting individual psychology, reducing barriers and cognitive burdens, and providing incentives. The majority of interventions (54%) aimed to reduce barriers or cognitive burdens, with improving comprehension (27%) as the most common specific strategy identified. For recruitment, the most common behavioral strategies tested were building legitimacy or trust (38%) and framing risks and benefits (32%), while financial or material incentives (32%) and reducing financial, time, and social barriers (32%) were most common for retention interventions. Among interventions tested in randomized controlled trials, 51% had a null effect on research participant engagement, and 30% had a statistically significant positive effect. DISCUSSION: Clinical researchers have tested a wide range of interventions that leverage distinct behavioral strategies to achieve improved research participant recruitment and retention. Common behavioral strategies include building legitimacy or trust between research teams and participants, as well as improving participant comprehension of trial objectives and procedures. The high frequency of null effects among tested interventions suggests challenges in selecting the optimal interventions for increasing research participant engagement, although the proposed behavioral strategy categories can serve as a conceptual framework for developing and testing future interventions.