Ultra-hypofractionated radiotherapy (UHF RT) is revolutionizing the treatment approach for low- and intermediate-risk prostate cancer patients. This study reports the planning process of UHF RT utilizing the cone beam computed tomography (CBCT)-based online adaptive radiotherapy (OART) treatment with the Ethos system, focusing on a comparative analysis between OART and image-guided radiotherapy (IGRT) plans. We also assessed the pre-planning capabilities of the Ethos system against the CyberKnife (CK) (Accuray, Sunnyvale, CA) system. A 66-year-old patient, diagnosed with prostatic acinar adenocarcinoma confirmed via biopsy and presenting with elevated prostate-specific antigen (PSA) levels, underwent UHF OART treatment using the Ethos system. The planning encompassed delineating the gross target volume (GTV) as the prostate, while the clinical target volume (CTV) comprised the prostate and proximal seminal vesicle. The planning target volume (PTV) was derived from the CTV with a 5 mm external margin except for a 3 mm posterior margin. A simultaneous integrated boost (SIB) technique was employed, delivering 40 Gy in five fractions (8 Gy per fraction) to the gross tumor volume (GTV) and 36.25 Gy in five fractions (7.25 Gy per fraction) to the remaining part of the planning target volume (PTV), with treatments scheduled biweekly. We compared OART and IGRT plans and conducted a comparative analysis between Ethos planning and the CK system for pre-planning assessment. When comparing Ethos planning and CK plans, Ethos demonstrated slightly better target coverage and organ-at-risk (OAR) sparing. However, CK plans showed superior containment of low-dose spillage, particularly at 50% and 25% iso-doses, due to non-coplanar beam arrangements. Our results demonstrated that OART plans yielded superior target coverage and improved OAR sparing compared to IGRT plans. Notably, the entire OART process, from planning to delivery, was accomplished within 27 minutes. The Ethos OART system\'s ability to adapt to daily anatomical changes, efficient workflow, and superior OAR-sparing capabilities make it a promising option for prostate cancer treatment using UHF RT.

Automated planning has surged in popularity within external beam radiation therapy in recent times. Leveraging insights from previous clinical knowledge could enhance auto-planning quality. In this work, we evaluated the performance of Ethos automated planning with knowledge-based guidance, specifically using Rapidplan (RP). Seventy-four patients with head-and-neck (HN) cancer and 37 patients with prostate cancer were used to construct separate RP models. Additionally, 16 patients from each group (HN and prostate) were selected to assess the performance of Ethos auto-planning results. Initially, a template-based Ethos plan (Non-RP plan) was generated, followed by integrating the corresponding RP model\'s DVH estimates into the optimization process to generate another plan (RP plan). We compared the target coverage, OAR doses, and total monitor units between the non-RP and RP plans. Both RP and non-RP plans achieved comparable target coverage in HN and Prostate cases, with a negligible difference of less than 0.5% (p > 0.2). RP plans consistently demonstrated lower doses of OARs in both HN and prostate cases. Specifically, the mean doses of OARs were significantly reduced by 9% (p < 0.05). RP plans required slightly higher monitor units in both HN and prostate sites (p < 0.05), however, the plan generation time was almost similar (p > 0.07). The inclusion of the RP model reduced the OAR doses, particularly reducing the mean dose to critical organs compared to non-RP plans while maintaining similar target coverage. Our findings provide valuable insights for clinics adopting Ethos planning, potentially enhancing the auto-planning to operate optimally.

UNASSIGNED: To evaluate the feasibility to use a standard Ethos planning template to treat left-sided breast cancer with regional lymph nodes.
UNASSIGNED: The tuning cohort of 5 patients was used to create a planning template. The validation cohort included 15 patients treated for a locally advanced left breast cancer randomly enrolled. The Ethos planning template was tuned using standard 3 partial arc VMAT and two collimator rotation configurations: 45/285/345° and 30/60/330°. Re-planning was performed automatically using the template without editing. The study was conducted with a schedule of 42.3 Gy in 18 fractions to the breast/chestwall, internal mammary chain (IMC) and regional lymph nodes (\"Nodes\"). The PTV was defined as a 3D extension of the CTV with a margin of 7 mm, excluding the 5mm below the skin. The manual treatment plans were performed using Eclipse treatment planning system with AAA and PO algorithms (v15.6) and a manual arc VMAT configuration and imported in Ethos TPS (v1.1) for a dose calculation with Ethos Acuros algorithm. The automated plans were compared with the manual plans using PTV and CTV coverage, homogeneity and conformity indices (HI and CN) and doses to organs at risk (OAR) via DVH metrics. For each plan, the patient quality assurance (QA) were performed using Mobius3D and gamma index. Finally, two breast radiation oncologists performed a blinded assessment of the clinical acceptability of each of the three plans (manual and automated) for each patient.
UNASSIGNED: The manual and automated plans provided suitable treatment planning as regards dose constraints. The dosimetric comparison showed the CTV_breast D99% were significantly improved with both automated plans (p< 0,002) while PTV coverage was comparable. The doses to the organs at risk were equivalent for the three plans. Concerning treatment delivery, the Ethos-45° and Ethos-30° plans led to an increase in MUs compared to the manual plans, without affecting the beam on time. The average gamma index pass rates remained consistently above 98% regardless of the type of plan utilized. In the blinded evaluation, clinicians 1 and 2 assessed 13 out of 15 plans for Ethos 45° and 11 out of 15 plans for Ethos 30° as clinically acceptable.
UNASSIGNED: Using a standard planning template for locally advanced breast cancer, the Ethos TPS provided automated plans that were clinically acceptable and comparable in quality to manually generated plans. Automated plans also dramatically reduce workflow and operator variability.

Cone-beam computed tomography (CBCT)-based online adaptation is increasingly being introduced into many clinics. Upon implementation of a new treatment technique, a prospective risk analysis is required and enhances workflow safety. We conducted a risk analysis using Failure Mode and Effects Analysis (FMEA) upon the introduction of an online adaptive treatment programme (Wegener et al., Z Med Phys. 2022). A prospective risk analysis, lacking in-depth clinical experience with a treatment modality or treatment machine, relies on imagination and estimates of the occurrence of different failure modes. Therefore, we systematically documented all irregularities during the first year of online adaptation, namely all cases in which quality assurance detected undesired states potentially leading to negative consequences. Additionally, the quality of automatic contouring was evaluated. Based on those quantitative data, the risk analysis was updated by an interprofessional team. Furthermore, a hypothetical radiation therapist-only workflow during adaptive sessions was included in the prospective analysis, as opposed to the involvement of an interprofessional team performing each adaptive treatment. A total of 126 irregularities were recorded during the first year. During that time period, many of the previously anticipated failure modes (almost) occurred, indicating that the initial prospective risk analysis captured relevant failure modes. However, some scenarios were not anticipated, emphasizing the limits of a prospective risk analysis. This underscores the need for regular updates to the risk analysis. The most critical failure modes are presented together with possible mitigation strategies. It was further noted that almost half of the reported irregularities applied to the non-adaptive treatments on this treatment machine, primarily due to a manual plan import step implemented in the institution\'s workflow.

OBJECTIVE: The aim of this study was to validate the Ethos Brief Index (EBI) in patients with Restless Legs Syndrome (RLS).
METHODS: A cross-sectional design, including 788 subjects with RLS (65% women, 70.8 years, SD 11.3) from the Swedish RLS Association, was used. A postal survey was sent out to collect data regarding socio demographics, comorbidities, and RLS-related treatment data. Questionnaires included were EBI, the Restless Legs Syndrome-6 Scale (RLS-6), Restless Legs Syndrome-Quality of Life questionnaire (RLSQoL), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS). The validity and reliability of the EBI were investigated using Rasch and confirmatory factor analysis (CFA) models. Measurement invariance, unidimensionality, and differential item functioning (DIF) across age and gender groups, as well as insomnia, daytime sleepiness, RLS-related QoL and RLS severity were assessed.
RESULTS: The results supported the unidimensionality of the EBI in the CFA (i.e., explaining 61.5% of the variance) and the Rasch model. The reliability of the EBI was confirmed using composite reliability and Cronbach\'s alpha. No DIF was identified for gender, age, insomnia, daytime sleepiness, RLS severity or RLS-related QoL.
CONCLUSIONS: The EBI showed good validity and reliability and operated equivalently for male and female patients with RLS. Accordingly, healthcare professionals can use the EBI as a psychometrically sound tool to explore and identify patient-centered problems related to the whole life situation.

The Ethos (Varian Medical Systems) radiotherapy device combines semi-automated anatomy detection and plan generation for cone beam computer tomography (CBCT)-based daily online adaptive radiotherapy (oART). However, CBCT offers less soft tissue contrast than magnetic resonance imaging (MRI). This work aims to present the clinical workflow of CBCT-based oART with shuttle-based offline MR guidance.
From February to November 2023, 31 patients underwent radiotherapy on the Ethos (Varian, Palo Alto, CA, USA) system with machine learning (ML)-supported daily oART. Moreover, patients received weekly MRI in treatment position, which was utilized for daily plan adaptation, via a shuttle-based system. Initial and adapted treatment plans were generated using the Ethos treatment planning system. Patient clinical data, fractional session times (MRI + shuttle transport + positioning, adaptation, QA, RT delivery) and plan selection were assessed for all fractions in all patients.
In total, 737 oART fractions were applied and 118 MRIs for offline MR guidance were acquired. Primary sites of tumors were prostate (n = 16), lung (n = 7), cervix (n = 5), bladder (n = 1) and endometrium (n = 2). The treatment was completed in all patients. The median MRI acquisition time including shuttle transport and positioning to initiation of the Ethos adaptive session was 53.6 min (IQR 46.5-63.4). The median total treatment time without MRI was 30.7 min (IQR 24.7-39.2). Separately, median adaptation, plan QA and RT times were 24.3 min (IQR 18.6-32.2), 0.4 min (IQR 0.3-1,0) and 5.3 min (IQR 4.5-6.7), respectively. The adapted plan was chosen over the scheduled plan in 97.7% of cases.
This study describes the first workflow to date of a CBCT-based oART combined with a shuttle-based offline approach for MR guidance. The oART duration times reported resemble the range shown by previous publications for first clinical experiences with the Ethos system.

OBJECTIVE: Field size limitations on Halcyon and Ethos treatment machines largely preclude use of the conventional monoisocentric three-field technique for breast/chest wall and regional lymph nodes. We present an alternative, IMRT-based planning approach that facilitates treatment on Halcyon and Ethos while preserving plan quality.
METHODS: Eight breast and regional node cases (four left-sided, four right-sided) were planned for an Ethos machine using a 15-17 field IMRT technique. Institutional plan quality metrics for CTV and PTV coverage and OAR sparing were assessed. Five plans (four right-sided, one left-sided) were also planned using a hybrid 3D multisocenter technique. CTV coverage and OAR sparing were compared to the IMRT plans. Eclipse scripting tools were developed to aid in beam placement and plan evaluation through a set of dosimetric scorecards, and both are shared publicly.
RESULTS: On average, the IMRT plans achieved breast CTV and PTV coverage at 50 Gy of 97.9% and 95.7%, respectively. Supraclavicular CTV and PTV coverages at 45 Gy were 100% and 95.5%. Axillary lymph node CTV and PTV coverages at 45 Gy were 100% and 97.1%, and IMN CTV coverage at 45 Gy was 99.2%. Mean ipsilateral lung V20 Gy was 19.3%, and average mean heart dose was 1.6 Gy for right-sided cases and 3.0 Gy for left-sided. In comparison to the hybrid 3D plans, IMRT plans achieved higher breast and supraclavicular CTV coverage (99.9% vs. 98.6% and 99.9% vs. 93.4%), higher IMN coverage (99.6% vs. 78.2%), and lower ipsilateral lung V20 Gy (19.6% vs. 28.2%).
CONCLUSIONS: Institutional plan quality benchmarks were achieved for all eight cases using the IMRT-based planning approach. The IMRT-based planning approach offered superior conformity and OAR sparing than a competing hybrid 3D approach.

OBJECTIVE: High-quality CBCT and AI-enhanced adaptive planning techniques allow CBCT-guided stereotactic adaptive radiotherapy (CT-STAR) to account for inter-fractional anatomic changes. Studies of intra-fractional respiratory motion management with a surface imaging solution for CT-STAR have not been fully conducted. We investigated intra-fractional motion management in breath-hold Ethos-based CT-STAR and CT-SBRT (stereotactic body non-adaptive radiotherapy) using optical surface imaging combined with onboard CBCTs.
METHODS: Ten cancer patients with mobile lower lung or upper abdominal malignancies participated in an IRB-approved clinical trial (Phase I) of optical surface image-guided Ethos CT-STAR/SBRT. In the clinical trial, a pre-configured gating window (± 2 mm in AP direction) on optical surface imaging was used for manually triggering intra-fractional CBCT acquisition and treatment beam irradiation during breath-hold (seven patients for the end of exhalation and three patients for the end of inhalation). Two inter-fractional CBCTs at the ends of exhalation and inhalation in each fraction were acquired to verify the primary direction and range of the tumor/imaging-surrogate (donut-shaped fiducial) motion. Intra-fractional CBCTs were used to quantify the residual motion of the tumor/imaging-surrogate within the pre-configured breath-hold window in the AP direction. Fifty fractions of Ethos RT were delivered under surface image-guidance: Thirty-two fractions with CT-STAR (adaptive RT) and 18 fractions with CT-SBRT (non-adaptive RT). The residual motion of the tumor was quantified by determining variations in the tumor centroid position. The dosimetric impact on target coverage was calculated based on the residual motion.
RESULTS: We used 46 fractions for the analysis of intra-fractional residual motion and 43 fractions for the inter-fractional motion analysis due to study constraints. Using the image registration method, 43 pairs of inter-fractional CBCTs and 100 intra-fractional CBCTs attached to dose maps were analyzed. In the motion range study (image registration) from the inter-fractional CBCTs, the primary motion (mean ± std) was 16.6 ± 9.2 mm in the SI direction (magnitude: 26.4 ± 11.3 mm) for the tumors and 15.5 ± 7.3 mm in the AP direction (magnitude: 20.4 ± 7.0 mm) for the imaging-surrogate, respectively. The residual motion of the tumor (image registration) from intra-fractional breath-hold CBCTs was 2.2 ± 2.0 mm for SI, 1.4 ± 1.4 mm for RL, and 1.3 ± 1.3 mm for AP directions (magnitude: 3.5 ± 2.1 mm). The ratio of the actual dose coverage to 99%, 90%, and 50% of the target volume decreased by 0.95 ± 0.11, 0.96 ± 0.10, 0.99 ± 0.05, respectively. The mean percentage of the target volume covered by the prescribed dose decreased by 2.8 ± 4.4%.
CONCLUSIONS: We demonstrated the intra-fractional motion-managed treatment strategy in breath-hold Ethos CT-STAR/SBRT using optical surface imaging and CBCT. While the controlled residual tumor motion measured at 3.5 mm exceeded the predetermined setup value of 2 mm, it is important to note that this motion still fell within the clinically acceptable range defined by the PTV margin of 5 mm. Nonetheless, additional caution is needed with intra-fractional motion management in breath-hold Ethos CT-STAR/SBRT using optical surface imaging and CBCT.

This study provides a concise and structured overview of a dosimetric comparison study conducted to assess the feasibility and effectiveness of 4 advanced radiotherapy techniques in treating brain metastases with hippocampus sparing and simultaneous integrated boost (HS-WBRT+SIB). Eleven patients with brain metastases previously treated with radiotherapy were included in the study. Planning CT scans with 2 mm slice thickness and MR imaging were used for contouring and dose prescription. The bilateral hippocampus and other organs at risk (OARs) were automatically contoured, and hippocampal avoidance regions (HAR) were defined as a 7 mm 3D expansion around the hippocampus. Gross tumor volume for each metastasis (GTVmet) and planning target volume for metastases (PTVmet) were delineated. The whole-brain CTV (CTVWB) and planning target volume for whole brain (PTVWB) were defined accordingly. Treatment planning and optimization were conducted using state-of-the-art radiotherapy techniques: Ethos, HyperArc, VMAT, and Tomotherapy. Tomotherapy achieved the highest D98% for PTVmet, indicating the best metastasis coverage. HyperArc plans showed the highest D98% for PTVWB, suggesting superior whole-brain coverage. Tomotherapy demonstrated significantly lower D98%, D2%, and Dmean values for the hippocampus, indicating its superiority in sparing the hippocampus. VMAT resulted in the lowest D2% values for the eyes, optic nerves, brainstem, and hypophysis, showing the best sparing of these critical structures. Tomotherapy consistently achieved lower Dmean values for parotids, oral cavity, and lips compared to the other techniques. The dosimetric comparison revealed distinct strengths and weaknesses for each radiotherapy technique. Tomotherapy excelled in sparing the hippocampus, while VMAT showed promise in sparing OARs. HyperArc plans demonstrated the best overall whole-brain coverage. These findings should guide clinicians in selecting the most suitable technique based on patient characteristics and institutional resources.

UNASSIGNED: The aim of this study was to assess the feasibility of online adaptive radiotherapy with Ethos for breast cancer.
UNASSIGNED: This retrospective study included 20 breast cancer patients previously treated with TrueBeam. All had undergone breast surgery for different indications (right/left, lumpectomy/mastectomy) and were evenly divided between these four cases, with five extended cone beam computed tomography (CBCT) scans per patient. The dataset was used in an Ethos emulator to test the full adaptive workflow. The contours generated by artificial intelligence (AI) for the influencers (left and right breasts and lungs, heart) and elastic or rigid propagation for the target volumes (internal mammary chain (IMC) and clavicular lymph nodes (CLNs)) were compared to the initial contours delineated by the physician using two metrics: Dice similarity coefficient (DICE) and Hausdorff 95% distance (HD95). The repeatability of influencer generation was investigated. The times taken by the emulator to generate contours, optimize plans, and calculate doses were recorded. The quality of the scheduled and adapted plans generated by Ethos was assessed using planning target volume (PTV) coverage, homogeneity indices (HIs), and doses to organs at risk (OARs) via dose-volume histogram (DVH) metrics. Quality assurance (QA) of the treatment plans was performed using an independent portal dosimetry tool (EpiQA) and gamma index.
UNASSIGNED: On average, the DICE for the influencers was greater than 0.9. Contours resulting from rigid propagation had a higher DICE and a lower HD95 than those resulting from elastic deformation but remained below the values obtained for the influencers: DICE values were 0.79 ± 0.11 and 0.46 ± 0.17 for the CLN and IMC, respectively. Regarding the repeatability of the influencer segmentation, the DICE was close to 1, and the mean HD95 was strictly less than 0.15 mm. The mean time was 73 ± 4 s for contour generation per AI and 80 ± 9 s for propagations. The average time was 53 ± 3 s for dose calculation and 125 ± 9 s for plan optimization. A dosimetric comparison of scheduled and adapted plans showed a significant difference in PTV coverage: dose received by 95% of the volume (D95%) values were higher and closer to the prescribed doses for adapted plans. Doses to organs at risk were similar. The average gamma index for quality assurance of adapted plans was 99.93 ± 0.38 for a 3%/3mm criterion.
UNASSIGNED: This study comprehensively evaluated the Ethos® adaptive workflow for breast cancer and its potential technical limitations. Although the results demonstrated the high accuracy of AI segmentation and the superiority of adapted plans in terms of target volume coverage, a medical assessment is still required.