Master Breast Radiation Planning: Simple Guide for Radiation Oncology Residents.

This article focuses on various aspects of breast radiation treatment planning, from simulation to field design. It covers the most common techniques including tangents, mono isocentric, dual isocentric, electron-photon match, and VMAT. This can serve as a guide for radiation oncology residents and medical students to advance their understanding of key aspects of breast radiation treatment and planning processes.

Multimodal radiotherapy dose prediction using a multi-task deep learning model.

BACKGROUND: In radiation therapy (RT), accelerated partial breast irradiation (APBI) has emerged as an increasingly preferred treatment modality over conventional whole breast irradiation due to its targeted dose delivery and shorter course of treatment. APBI can be delivered through various modalities including Cobalt-60-based systems and linear accelerators with C-arm, O-ring, or robotic arm design. Each modality possesses distinct features, such as beam energy or the degrees of freedom in treatment planning, which influence their respective dose distributions. These modality-specific considerations emphasize the need for a quantitative approach in determining the optimal dose delivery modality on a patient-specific basis. However, manually generating treatment plans for each modality across every patient is time-consuming and clinically impractical. PURPOSE: We aim to develop an efficient and personalized approach for determining the optimal RT modality for APBI by training predictive models using two different deep learning-based convolutional neural networks. The baseline network performs a single-task (ST), predicting dose for a single modality. Our proposed multi-task (MT) network, which is capable of leveraging shared information among different tasks, can concurrently predict dose distributions for various RT modalities. Utilizing patient-specific input data, such as a patient's computed tomography (CT) scan and treatment protocol dosimetric goals, the MT model predicts patient-specific dose distributions across all trained modalities. These dose distributions provide patients and clinicians quantitative insights, facilitating informed and personalized modality comparison prior to treatment planning. METHODS: The dataset, comprising 28 APBI patients and their 92 treatment plans, was partitioned into training, validation, and test subsets. Eight patients were dedicated to the test subset, leaving 68 treatment plans across 20 patients to divide between the training and validation subsets. ST models were trained for each modality, and one MT model was trained to predict doses for all modalities simultaneously. Model performance was evaluated across the test dataset in terms of Mean Absolute Percent Error (MAPE). We conducted statistical analysis of model performance using the two-tailed Wilcoxon signed-rank test. RESULTS: Training times for five ST models ranged from 255 to 430 min per modality, totaling 1925 min, while the MT model required 2384 min. MT model prediction required an average of 1.82 s per patient, compared to ST model predictions at 0.93 s per modality. The MT model yielded MAPE of 1.1033 ± 0.3627% as opposed to the collective MAPE of 1.2386 ± 0.3872% from ST models, and the differences were statistically significant (p = 0.0003, 95% confidence interval = [-0.0865, -0.0712]). CONCLUSION: Our study highlights the potential benefits of a MT learning framework in predicting RT dose distributions across various modalities without notable compromises. This MT architecture approach offers several advantages, such as flexibility, scalability, and streamlined model management, making it an appealing solution for clinical deployment. With such a MT model, patients can make more informed treatment decisions, physicians gain more quantitative insight for pre-treatment decision-making, and clinics can better optimize resource allocation. With our proposed goal array and MT framework, we aim to expand this work to a site-agnostic dose prediction model, enhancing its generalizability and applicability.

Beyond conventional bounds: Surpassing system limits for stereotactic ablative (SAbR) lung radiotherapy using CBCT-based adaptive planning system.

PURPOSE: Online adaptive radiotherapy relies on a high degree of automation to enable rapid planning procedures. The Varian Ethos intelligent optimization engine (IOE) was originally designed for conventional treatments so it is crucial to provide clear guidance for lung SAbR plans. This study investigates using the Ethos IOE together with adaptive-specific optimization tuning structures we designed and templated within Ethos to mitigate inter-planner variability in meeting RTOG metrics for both online-adaptive and offline SAbR plans. METHODS: We developed a planning strategy to automate the generation of tuning structures and optimization. This was validated by retrospective analysis of 35 lung SAbR cases (total 105 fractions) treated on Ethos. The effectiveness of our planning strategy was evaluated by comparing plan quality with-and-without auto-generated tuning structures. Internal target volume (ITV) contour was compared between that drawn from CT simulation and from cone-beam CT (CBCT) at time of treatment to verify CBCT image quality and treatment effectiveness. Planning strategy robustness for lung SAbR was quantified by frequency of plans meeting reference plan RTOG constraints. RESULTS: Our planning strategy creates a gradient within the ITV with maximum dose in the core and improves intermediate dose conformality on average by 2%. ITV size showed no significant difference between those contoured from CT simulation and first fraction, and also trended towards decreasing over course of treatment. Compared to non-adaptive plans, adaptive plans better meet reference plan goals (37% vs. 100% PTV coverage compliance, for scheduled and adapted plans) while improving plan quality (improved GI (gradient index) by 3.8%, CI (conformity index) by 1.7%). CONCLUSION: We developed a robust and readily shareable planning strategy for the treatment of adaptive lung SAbR on the Ethos system. We validated that automatic online plan re-optimization along with the formulated adaptive tuning structures can ensure consistent plan quality. With the proposed planning strategy, highly ablative treatments are feasible on Ethos.

Ultra-fastin vivodirectional dark-field x-ray imaging for visualising magnetic control of particles for airway gene delivery.

Objective.Magnetic nanoparticles can be used as a targeted delivery vehicle for genetic therapies. Understanding how they can be manipulated within the complex environment of live airways is key to their application to cystic fibrosis and other respiratory diseases.Approach.Dark-field x-ray imaging provides sensitivity to scattering information, and allows the presence of structures smaller than the detector pixel size to be detected. In this study, ultra-fast directional dark-field synchrotron x-ray imaging was utlilised to understand how magnetic nanoparticles move within a live, anaesthetised, rat airway under the influence of static and moving magnetic fields.Main results.Magnetic nanoparticles emerging from an indwelling tracheal cannula were detectable during delivery, with dark-field imaging increasing the signal-to-noise ratio of this event by 3.5 times compared to the x-ray transmission signal. Particle movement as well as particle retention was evident. Dynamic magnetic fields could manipulate the magnetic particlesin situ. Significance.This is the first evidence of the effectiveness ofin vivodark-field imaging operating at these spatial and temporal resolutions, used to detect magnetic nanoparticles. These findings provide the basis for further development toward the effective use of magnetic nanoparticles, and advance their potential as an effective delivery vehicle for genetic agents in the airways of live organisms.

Adapt-On-Demand: A Novel Strategy for Personalized Adaptive Radiation Therapy for Locally Advanced Lung Cancer.

PURPOSE: Real-time adaptation of thoracic radiation plans is compelling because offline adaptive experiences show that tumor volumes and lung anatomy can change during therapy. We present and analyze a novel adaptive-on-demand (AOD) workflow combining online adaptive radiation therapy (o-ART) on the ETHOS system with image guided radiation therapy delivery on a Halcyon unit for conventional fractionated radiation therapy of locally advanced lung cancer (LALC). METHODS AND MATERIALS: We analyzed 26 patients with LALC treated with the AOD workflow, adapting weekly. We timed segments of the workflow to evaluate efficiency in a real-world clinic. Target coverage and organ at risk (OAR) doses were compared between adaptive plans (ADP) and nonadaptive scheduled plans (SCH). Planning robustness was evaluated by the frequency of preplanning goals achieved in ADP plans, stratified by tumor volume change. RESULTS: The AOD workflow was achievable within 30 minutes for most radiation fractions. Over the course of therapy, we observed an average 26.6% ± 23.3% reduction in internal target volume (ITV). Despite these changes, with o-ART, ITV and planning target volume (PTV) coverage (V100%) was 99.2% and 93.9% for all members of the cohort, respectively. This represented a 2.9% and 6.8% improvement over nonadaptive plans (P < .05), respectively. For tumors that grew >10%, V100% was 93.1% for o-ART and 76.4% for nonadaptive plans, representing a median 17.2% improvement in the PTV coverage (P < .05). In these plans, critical OAR constraints were met 94.1% of the time, whereas in nonadaptive plans, this figure was 81.9%. This represented reductions of 1.32 Gy, 1.34 Gy, or 1.75 Gy in the heart, esophagus, and lung, respectively. The effect was larger when tumors had shrunk more than 10%. Regardless of tumor volume alterations, the PTV/ITV coverage was achieved for all adaptive plans. Exceptional cases, where dose constraints were not met, were due to large initial tumor volumes or tumor growth. CONCLUSIONS: The AOD workflow is efficient and robust in responding to anatomic changes in LALC patients, providing dosimetric advantages over standard therapy. Weekly adaptation was adequate to keep pace with changes. This approach is a feasible alternative to conventional offline replanning workflows for managing anatomy changes in LALC radiation therapy.

Effect of elexacaftor-tezacaftor-ivacaftor on nasal potential difference and lung function in Phe508del rats.

Introduction: Phe508del is the most common cystic fibrosis transmembrane conductance regulator (CFTR) gene variant that results in the recessive genetic disorder cystic fibrosis (CF). The recent development of highly effective CFTR modulator therapies has led to significant health improvements in individuals with this mutation. While numerous animal models of CF exist, few have a CFTR mutation that is amenable to the triple combination therapy elexacaftor-tezacaftor-ivacaftor (ETI). Methods: To determine the responsiveness of Phe508del rats to ETI, a baseline nasal potential difference was measured. Subsequently, they received ETI daily for 14 days, after which post-treatment nasal potential difference, lung mechanics (via flexiVent) and lung ventilation (via X-ray Velocimetry) were assessed. Results: Chloride ion transport in nasal airways was restored in Phe508del rats treated with ETI, but neither lung mechanics nor ventilation were significantly altered. Discussion: These findings validate the usefulness of this rat model for future investigations of modulator therapy in CF.

In silico evaluation and feasibility of near margin-less head and neck daily adaptive radiotherapy.

OBJECTIVE: We explore the potential dosimetric benefits of reducing treatment volumes through daily adaptive radiation therapy for head and neck cancer (HNC) patients using the Ethos system/Intelligent Optimizer Engine (IOE). We hypothesize reducing treatment volumes afforded by daily adaption will significantly reduce the dose to adjacent organs at risk. We also explore the capability of the Ethos IOE to accommodate this highly conformal approach in HNC radiation therapy. METHODS: Ten HNC patients from a phase II trial were chosen, and their cone-beam CT (CBCT) scans were uploaded to the adaptive RT (ART) emulator. A new initial reference plan was generated using both a 1 mm and 5 mm planning target volume (PTV) expansion. Daily adaptive ART plans (1 mm) were simulated from the clinical CBCT taken every fifth fraction. Additionally, using physician-modified ART contours the larger 5 mm plan was recalculated on this recontoured on daily anatomy. Changes in target and OAR contours were measured using Dice coefficients as a surrogate of clinician effort. PTV coverage and organ-at-risk (OAR) doses were statistically compared, and the robustness of each ART plan was evaluated at fractions 5 and 35 to observe if OAR doses were within 3 Gy of pre-plan. RESULTS: This study involved six patients with oropharynx and four with larynx cancer, totaling 70 adaptive fractions. The primary and nodal gross tumor volumes (GTV) required the most adjustments, with median Dice scores of 0.88 (range: 0.80-0.93) and 0.83 (range: 0.66-0.91), respectively. For the 5th and 35th fraction plans, 80 % of structures met robustness criteria (quartile 1-3: 67-100 % and 70-90 %). Adaptive planning improved median PTV V100% coverage for doses of 70 Gy (96 % vs. 95.6 %), 66.5 Gy (98.5 % vs. 76.5 %), and 63 Gy (98.9 % vs. 74.9 %) (p < 0.03). Implementing ART with total volume reduction yielded median dose reductions of 7-12 Gy to key organs-at-risk (OARs) like submandibular glands, parotids, oral cavity, and constrictors (p < 0.05). CONCLUSIONS: The IOE enables feasible daily ART treatments with reduced margins while enhancing target coverage and reducing OAR doses for HNC patients. A phase II trial recently finished accrual and forthcoming analysis will determine if these dosimetric improvements correlate with improved patient-reported outcomes.

Pilot study of paediatric regional lung function assessment via X-ray velocimetry (XV) imaging in children with normal lungs and in children with cystic fibrosis.

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting autosomal recessive genetic condition. It is caused by mutations in the gene that encodes for a chloride and bicarbonate conducting transmembrane channel. X-ray velocimetry (XV) is a novel form of X-ray imaging that can generate lung ventilation data through the breathing cycle. XV technology has been validated in multiple animal models, including the ß-ENaC mouse model of CF lung disease. It has since been assessed in early-phase clinical trials in adult human subjects; however, there is a paucity of data in the paediatric cohort, including in CF. The aim of this pilot study was to investigate the feasibility of performing a single-centre cohort study in paediatric patients with CF and in those with normal lungs to demonstrate the appropriateness of proceeding with further studies of XV in these cohorts. METHODS AND ANALYSIS: This is a cross-sectional, single-centre, pilot study. It will recruit children aged 3-18 years to have XV lung imaging performed, as well as paired pulmonary function testing. The study will aim to recruit 20 children without CF with normal lungs and 20 children with CF. The primary outcome will be the feasibility of recruiting children and performing XV testing. Secondary outcomes will include comparisons between XV and current assessments of pulmonary function and structure. ETHICS AND DISSEMINATION: This project has ethical approval granted by The Women's and Children's Hospital Human Research Ethics Committee (HREC ID 2021/HRE00396). Findings will be disseminated through peer-reviewed publication and conferences. TRIAL REGISTRATION NUMBER: ACTRN12623000109606.

Accuracy of imaging grading in comparison to open laminectomy to evaluate pedicle screws positioning.

Study design: Prospective experimental study. Objective: To compare the accuracy of O-Arm-acquired radiographic and computed tomography (CT) evaluation of thoracic pedicle screw placement with open laminectomy in a simulation laboratory. Summary of background data: Improving surgical safety and procedural efficiency during thoracic posterior spine instrumentation is essential for decreasing complication rates and possible related risks. The most common way of verifying the position of pedicle screws during the surgical procedure and immediately postoperatively is to acquire intraoperative fluoroscopic images and plain radiographs of the spine, respectively. Laboratory simulated surgery is a valuable tool to evaluate the accuracy of those exams. Methods: Twenty simulation models of scoliosis from T3 to T7 were instrumented by five spine fellows (total of 200 pedicle screws), followed by radiographic and CT images acquired with the assistance of the O-Arm which were evaluated by three independent raters. A fellowship-trained spine neurosurgeon performed laminectomies on the instrumented levels and assessed pedicle integrity (gold standard). Results: Forty-eight breaches were identified in the axial direct view after laminectomy. Of those, eighteen breaches were classified as unacceptable. Regarding the sagittal direct view, four breaches were observed, three of which were classified as unacceptable. Overall, both O-arm radiographic and CT evaluations had a significantly high negative predicted value but a low positive predicted value to identify unacceptable breaches, especially in the sagittal plane. The frequency of missed breaches by all three examiners was high, particularly in the sagittal plane. Conclusion: Postoperative evaluation of pedicle screws using O-arm-acquired radiographic or CT images may underdiagnose the presence of breaches. In our study, sagittal breaches were more difficult to diagnose than axial breaches. Although most breaches do not have clinical repercussions, this study suggests that this modality of postoperative radiographic assessment may be inaccurate. Level of evidence: 4.

Fetal drug exposure after maternally administered CFTR modulators Elexacaftor/Tezacaftor/Ivacaftor in a rat model.

BACKGROUND: The potential effects of the very effective cystic fibrosis triple combination drug, Elexacaftor/Tezacaftor/Ivacaftor (ETI) in pregnancy on prenatal development of offspring remain largely unknown. RESEARCH QUESTION: We aimed to investigate the fetal tissue distribution pattern of maternally administered ETI by placental transfer in the rat fetuses. STUDY DESIGN AND METHODS: Sprague Dawley pregnant rats were administered ETI (6.7 mg/kg/d elexacaftor + 3.5 mg/kg/d tezacaftor + 25 mg/kg/d ivacaftor) traced with [3 H]-ivacaftor in single dose acute experiments (intraperitoneal injection) or treated orally with ETI (the same dose) for 7 days in sub-chronic experiments. Fetal tissue samples were collected at embryonic day (E) 19 and analyzed using liquid scintillation counting for acute experiments or liquid chromatography-mass spectrometry for sub-chronic experiments. RESULTS: On day E19, after acute exposure, the entry of ivacaftor into fetal brain (brain/plasma concentration ratios <50%) was significantly lower than to other tissues (>100%). However, after sub-chronic exposure, the entry of all 3 components into the developing brain was comparably extensive as into other tissues (tissue/plasma ratios, 260 - 1000%). Each component of ETI accumulated in different fetal tissues to approximately equal extent. Inter-litter differences on fetal drug distribution were found in cortex for ivacaftor, muscle for tezacaftor and cortex and mid/hindbrain for elexacaftor. Fetal plasma concentrations of ETI (ng/mL) were variable between litters. The entry of ivacaftor and tezacaftor into adult brain appeared to be restricted (<100%). INTERPRETATION: Fetal rats are exposed to maternally ingested ETI after sub-chronic exposure, potentially impacting fetal development. The brain entry data highlights the need for attention be paid to any long-term potential effects ETI exposure could have on normal brain development.

Simulation and pre-planning omitted radiotherapy (SPORT): a feasibility study for prostate cancer.

This study explored the feasibility of on-couch intensity modulated radiotherapy (IMRT) planning for prostate cancer (PCa) on a cone-beam CT (CBCT)-based online adaptive RT platform without an individualized pre-treatment plan and contours. Ten patients with PCa previously treated with image-guided IMRT (60 Gy/20 fractions) were selected. In contrast to the routine online adaptive RT workflow, a novel approach was employed in which the same preplan that was optimized on one reference patient was adapted to generate individual on-couch/initial plans for the other nine test patients using Ethos emulator. Simulation CTs of the test patients were used as simulated online CBCT (sCBCT) for emulation. Quality assessments were conducted on synthetic CTs (sCT). Dosimetric comparisons were performed between on-couch plans, on-couch plans recomputed on the sCBCT and individually optimized plans for test patients. The median value of mean absolute difference between sCT and sCBCT was 74.7 HU (range 69.5-91.5 HU). The average CTV/PTV coverage by prescription dose was 100.0%/94.7%, and normal tissue constraints were met for the nine test patients in on-couch plans on sCT. Recalculating on-couch plans on the sCBCT showed about 0.7% reduction of PTV coverage and a 0.6% increasing of hotspot, and the dose difference of the OARs was negligible (<0.5 Gy). Hence, initial IMRT plans for new patients can be generated by adapting a reference patient's preplan with online contours, which had similar qualities to the conventional approach of individually optimized plan on the simulation CT. Further study is needed to identify selection criteria for patient anatomy most amenable to this workflow.

Forward-in-time simulation of chromosomal rearrangements: The invisible backbone that sustains long-term adaptation.

While chromosomal rearrangements are ubiquitous in all domains of life, very little is known about their evolutionary significance, mostly because, apart from a few specifically studied and well-documented mechanisms (interaction with recombination, gene duplication, etc.), very few models take them into account. As a consequence, we lack a general theory to account for their direct and indirect contributions to evolution. Here, we propose Aevol, a forward-in-time simulation platform specifically dedicated to unravelling the evolutionary significance of chromosomal rearrangements (CR) compared to local mutations (LM). Using the platform, we evolve populations of organisms in four conditions characterized by an increasing diversity of mutational operators-from substitutions alone to a mix of substitutions, InDels and CR-but with a constant global mutational rate. Despite being almost invisible in the phylogeny owing to the scarcity of their fixation in the lineages, we show that CR make a decisive contribution to the evolutionary dynamics by comparing the outcome in these four conditions. As expected, chromosomal rearrangements allow fast expansion of the gene repertoire through gene duplication, but they also reduce the effect of diminishing-returns epistasis, hence sustaining adaptation on the long-run. At last, we show that chromosomal rearrangements tightly regulate the size of the genome through indirect selection for reproductive robustness. Overall, these results confirm the need to improve our theoretical understanding of the contribution of chromosomal rearrangements to evolution and show that dedicated platforms like Aevol can efficiently contribute to this agenda.

Noncontact Respiratory Motion Detection in Anesthetized Rodents.

Small animal physiology studies are often complicated, but the level of complexity is greatly increased when performing live-animal X-ray imaging studies at synchrotron radiation facilities. This is because these facilities are typically not designed specifically for biomedical research, and the animals and image detectors are located away from the researchers in a radiation enclosure. In respiratory X-ray imaging studies one challenge is the detection of respiration in free-breathing anaesthetised rodents, to enable images to be acquired at specific phases of the breath and for detecting changes in respiratory rate. We have previously used a Philtec RC60 sensor interfaced to a PowerLab data acquisition system and custom-designed timing hub to perform this task. Here we evaluated the Panasonic HL-G108 for respiratory sensing. The performance of the two sensors for accurate and reliable breath detection was directly compared using a single anesthetized rat. We also assessed how an infrared heat lamp used to maintain body temperature affected sensor performance. Based on positive results from these comparisons, the HL-G108 sensor was then used for respiratory motion detection in tracheal X-ray imaging studies of 21 rats at the SPring-8 Synchrotron, including its use for gated image acquisition. The results of that test were compared to a similar imaging study that used the RC60 for respiratory detection in 19 rats. Finally, the HL-G108 sensor was tested on 5 mice to determine its effectiveness on smaller species. The results showed that the HL-G108 is much more robust and easier to configure than the RC60 sensor and produces an analog signal that is amenable to stable peak detection. Furthermore, gated image acquisition produced sequences with substantially reduced motion artefacts, enabling the additional benefit of reduced radiation dose through the application of shuttering. Finally, the mouse experiments showed that the HL-G108 is equally capable of detecting respiration in this smaller species.

Considerations for intensity modulated total body or total marrow and lymphoid irradiation.

We compiled a sampling of the treatment techniques of intensity-modulated total body irradiation, total marrow irradiation and total marrow and lymphoid irradiation utilized by several centers across North America and Europe. This manuscript does not serve as a consensus guideline, but rather is meant to serve as a convenient reference for centers that are considering starting an intensity-modulated program.

Repeat or single-dose lentiviral vector administration to mouse lungs? It's all about the timing.

Lentiviral vectors are attractive delivery vehicles for cystic fibrosis gene therapy owing to their low immunogenicity and ability to integrate into the host cell genome, thereby producing long-term, stable gene expression. Nonetheless, repeat dosing may be required to increase initial expression levels, and/or boost levels when they wane. The primary aim of this study was to determine if repeat dosing of a VSV-G pseudotyped LV vector delivered into mouse lungs is more effective than a single dose. C57Bl/6 mouse lungs were conditioned with lysophosphatidylcholine, followed one-hour later by a LV vector carrying the luciferase reporter gene, using six different short-term (≤1 wk) and long-term (>1 wk) dosing schedules. Luciferase expression was quantified using bioluminescence imaging over 12 months. Most dosing schedules produced detectable bioluminescence over the 12-month period, but the shorter intervals (≤1 wk) produced higher levels of flux than the longest interval (five doses at least 1-month apart). Ex vivo lung analysis at 12 months showed that the estimated mean flux for the group that received two doses 1-week apart was significantly greater than the single dose group and the two groups that received doses over a period greater than 1-week. These results suggest that early consecutive multiple doses are more effective at improving gene expression in mouse lungs at 12 months, than longer repeat dosing intervals.

Changes in Essential Fatty Acids and Ileal Genes Associated with Metabolizing Enzymes and Fatty Acid Transporters in Rodent Models of Cystic Fibrosis.

Cystic fibrosis (CF), the result of mutations in the CF transmembrane conductance regulator (CFTR), causes essential fatty acid deficiency. The aim of this study was to characterize fatty acid handling in two rodent models of CF; one strain which harbors the loss of phenylalanine at position 508 (Phe508del) in CFTR and the other lacks functional CFTR (510X). Fatty acid concentrations were determined using gas chromatography in serum from Phe508del and 510X rats. The relative expression of genes responsible for fatty acid transport and metabolism were quantified using real-time PCR. Ileal tissue morphology was assessed histologically. There was an age-dependent decrease in eicosapentaenoic acid and the linoleic acid:α-linolenic acid ratio, a genotype-dependent decrease in docosapentaenoic acid (n-3) and an increase in the arachidonic acid:docosahexaenoic acid ratio in Phe508del rat serum, which was not observed in 510X rats. In the ileum, Cftr mRNA was increased in Phe508del rats but decreased in 510X rats. Further, Elvol2, Slc27a1, Slc27a2 and Got2 mRNA were increased in Phe508del rats only. As assessed by Sirius Red staining, collagen was increased in Phe508del and 510X ileum. Thus, CF rat models exhibit alterations in the concentration of circulating fatty acids, which may be due to altered transport and metabolism, in addition to fibrosis and microscopic structural changes in the ileum.

Evaluating machine learning enhanced intelligent-optimization-engine (IOE) performance for ethos head-and-neck (HN) plan generation.

PURPOSE: Varian Ethos utilizes novel intelligent-optimization-engine (IOE) designed to automate the planning. However, this introduced a black box approach to plan optimization and challenge for planners to improve plan quality. This study aims to evaluate machine-learning-guided initial reference plan generation approaches for head & neck (H&N) adaptive radiotherapy (ART). METHODS: Twenty previously treated patients treated on C-arm/Ring-mounted were retroactively re-planned in the Ethos planning system using a fixed 18-beam intensity-modulated radiotherapy (IMRT) template. Clinical goals for IOE input were generated using (1) in-house deep-learning 3D-dose predictor (AI-Guided) (2) commercial knowledge-based planning (KBP) model with universal RTOG-based population criteria (KBP-RTOG) and (3) an RTOG-based constraint template only (RTOG) for in-depth analysis of IOE sensitivity. Similar training data was utilized for both models. Plans were optimized until their respective criteria were achieved or DVH-estimation band was satisfied. Plans were normalized such that the highest PTV dose level received 95% coverage. Target coverage, high-impact organs-at-risk (OAR) and plan deliverability was assessed in comparison to clinical (benchmark) plans. Statistical significance was evaluated using a paired two-tailed student t-test. RESULTS: AI-guided plans were superior to both KBP-RTOG and RTOG-only plans with respect to clinical benchmark cases. Overall, OAR doses were comparable or improved with AI-guided plans versus benchmark, while they increased with KBP-RTOG and RTOG plans. However, all plans generally satisfied the RTOG criteria. Heterogeneity Index (HI) was on average <1.07 for all plans. Average modulation factor was 12.2 ± 1.9 (p = n.s), 13.1 ± 1.4 (p = <0.001), 11.5 ± 1.3 (p = n.s.) and 12.2 ± 1.9 for KBP-RTOG, AI-Guided, RTOG and benchmark plans, respectively. CONCLUSION: AI-guided plans were the highest quality. Both KBP-enabled and RTOG-only plans are feasible approaches as clinics adopt ART workflows. Similar to constrained optimization, the IOE is sensitive to clinical input goals and we recommend comparable input to an institution's planning directive dosimetric criteria.

Evaluation of plan quality and treatment efficiency in cranial stereotactic radiosurgery treatment plans with a variable source-to-axis distance.

INTRODUCTION: Radiotherapy deliveries with dynamic couch motions that shorten the source-to-axis distance (SAD) on a C-arm linac have the potential to increase treatment efficiency through the increase of the effective dose rate. In this investigation, we convert clinically deliverable volumetric modulated arc therapy (VMAT) and dynamic conformal arc (DCA) plans for cranial radiosurgery into virtual isocenter plans through implementation of couch trajectories that maintain the target at a shortened but variable SAD throughout treatment. MATERIALS AND METHODS: A randomly sampled population of patients treated with cranial radiosurgery from within the last three years were separated into groups with one, two, and three lesions. All plans had a single isocenter (regardless of number of targets), and a single prescription dose. Patient treatment plans were converted from their original delivery at a standard isocenter to a dynamic virtual isocenter in MATLAB. The virtual isocenter plan featured a variable isocenter position based upon the closest achievable source-to-target distance (referred to herein as a virtual source-to-axis distance [vSAD]) which avoided collision zones on a TrueBeam STx platform. Apertures were magnified according to the vSAD and monitor units at a given control point were scaled based on the inverse square law. Doses were calculated for the plans with a virtual isocenter in the Eclipse (v13.6.23) treatment planning system (TPS) and were compared with the clinical plans. Plan metrics (MU, Paddick conformity index, gradient index, and the volume receiving 12 Gy or more), normal brain dose-volume differences, as well as maximum doses received by organs at risk (OARs) were assessed. The values were compared between standard and virtual isocenter plans with Wilcoxon Sign Ranked tests to determine significance. A subset of the plans were mapped to the MAX-HD anthropomorphic phantom which contained an insert housing EBT3 GafChromic film and a PTW 31010 microion chamber for dose verification on a linac. RESULTS: Delivering plans at a virtual isocenter resulted in an average reduction of 20.9% (p = 3×10-6 ) and 20.6% (p = 3.0×10-6 ) of MUs across all VMAT and all DCA plans, respectively. There was no significant change in OAR max doses received by plans delivered at a virtual isocenter. The low dose wash (1.0-2.0 Gy or 5-11% of the prescription dose) was increased (by approximately 20 cc) for plans with three lesions. This was equivalent to a 2.7%-3.8% volumetric increase in normal tissue receiving the respective dose level when comparing the plan with a virtual isocenter to a plan with a standard isocenter. Gamma pass rates with a 5%/1mm analysis criteria were 96.40% ± 2.90% and 95.07% ± 3.10% for deliveries at standard and virtual isocenter, respectively. Absolute point dose agreements were within -0.36% ± 3.45% and -0.55% ± 3.39% for deliveries at a standard and virtual isocenter, respectively. Potential time savings per arc were found to have linear relationship with the monitor units delivered per arc (savings of 0.009 s/MU with an r2 = 0.866 when fit to plans with a single lesion). CONCLUSIONS: Converting clinical plans at standard isocenter to a virtual isocenter design did not show any losses to plan quality while simultaneously improving treatment efficiency through MU reductions.

To bead or not to bead: A review of Pseudomonas aeruginosa lung infection models for cystic fibrosis.

Cystic fibrosis (CF) lung disease is characterised by recurring bacterial infections resulting in inflammation, lung damage and ultimately respiratory failure. Pseudomonas aeruginosa is considered one of the most important lung pathogens in those with cystic fibrosis. While multiple cystic fibrosis animal models have been developed, many fail to mirror the cystic fibrosis lung disease of humans, including the colonisation by opportunistic environmental pathogens. Delivering bacteria to the lungs of animals in different forms is a way to model cystic fibrosis bacterial lung infections and disease. This review presents an overview of previous models, and factors to consider when generating a new P. aeruginosa lung infection model. The future development and application of lung infection models that more accurately reflect human cystic fibrosis lung disease has the potential to assist in understanding the pathophysiology of cystic fibrosis lung disease and for developing treatments.