Markerless liver online adaptive stereotactic radiotherapy: feasibility analysisCervantes.

Objective. Radio-opaque markers are recommended for image-guided radiotherapy in liver stereotactic ablative radiotherapy (SABR), but their implantation is invasive. We evaluate in thisin-silicostudy the feasibility of cone-beam computed tomography-guided stereotactic online-adaptive radiotherapy (CBCT-STAR) to propagate the target volumes without implanting radio-opaque markers and assess its consequence on the margin that should be used in that context.Approach. An emulator of a CBCT-STAR-dedicated treatment planning system was used to generate plans for 32 liver SABR patients. Three target volume propagation strategies were compared, analysing the volume difference between the GTVPropagatedand the GTVConventional, the vector lengths between their centres of mass (lCoM), and the 95th percentile of the Hausdorff distance between these two volumes (HD95). These propagation strategies were: (1) structure-guided deformable registration with deformable GTV propagation; (2) rigid registration with rigid GTV propagation; and (3) image-guided deformable registration with rigid GTV propagation. Adaptive margin calculation integrated propagation errors, while interfraction position errors were removed. Scheduled plans (PlanNon-adaptive) and daily-adapted plans (PlanAdaptive) were compared for each treatment fraction.Main results.The image-guided deformable registration with rigid GTV propagation was the best propagation strategy regarding tolCoM(mean: 4.3 +/- 2.1 mm), HD95 (mean 4.8 +/- 3.2 mm) and volume preservation between GTVPropagatedand GTVConventional. This resulted in a planning target volume (PTV) margin increase (+69.1% in volume on average). Online adaptation (PlanAdaptive) reduced the violation rate of the most important dose constraints ('priority 1 constraints', 4.2 versus 0.9%, respectively;p< 0.001) and even improved target volume coverage compared to non-adaptive plans (PlanNon-adaptive).Significance. Markerless CBCT-STAR for liver tumours is feasible using Image-guided deformable registration with rigid GTV propagation. Despite the cost in terms of PTV volumes, daily adaptation reduces constraints violation and restores target volumes coverage.

Assessment and validation of glottic motion using cone-beam CT and real-time cine MRI.

PURPOSE: This study aimed to assess the margin for the planning target volume (PTV) using the Van Herk formula. We then validated the proposed margin by real-time magnetic resonance imaging (MRI). METHODS: An analysis of cone-beam computed tomography (CBCT) data from early glottic cancer patients was performed to evaluate organ motion. Deformed clinical target volumes (CTV) after rigid registration were acquired using the Velocity program (Varian Medical Systems, Palo Alto, CA, USA). Systematic (Σ) and random errors (σ) were evaluated. The margin for the PTV was defined as 2.5 Σ + 0.7 σ according to the Van Herk formula. To validate this margin, we accrued healthy volunteers. Sagittal real-time cine MRI was conducted using the ViewRay system (ViewRay Inc., Oakwood Village, OH, USA). Within the obtained sagittal images, the vocal cord was delineated. The movement of the vocal cord was summed up and considered as the internal target volume (ITV). We then assessed the degree of overlap between the ITV and the PTV (vocal cord plus margins) by calculating the volume overlap ratio, represented as (ITV∩PTV)/ITV. RESULTS: CBCTs of 17 early glottic patients were analyzed. Σ and σ were 0.55 and 0.57 for left-right (LR), 0.70 and 0.60 for anterior-posterior (AP), and 1.84 and 1.04 for superior-inferior (SI), respectively. The calculated margin was 1.8 mm (LR), 2.2 mm (AP), and 5.3 mm (SI). Four healthy volunteers participated for validation. A margin of 3 mm (AP) and 5 mm (SI) was applied to the vocal cord as the PTV. The average volume overlap ratio between ITV and PTV was 0.92 (range 0.85-0.99) without swallowing and 0.77 (range 0.70-0.88) with swallowing. CONCLUSION: By evaluating organ motion by using CBCT, the margin was 1.8 (LR), 2.2 (AP), and 5.3 mm (SI). The margin acquired using CBCT fitted well in real-time cine MRI. Given that swallowing during radiotherapy can result in a substantial displacement, it is crucial to consider strategies aimed at minimizing swallowing and related motion.

Microplastic infiltration into mobile sediments.

This study investigates the dynamics of microplastic infiltration into non-stationary sandy sediments, a pressing environmental concern due to the rising prevalence of microplastics in aquatic ecosystems. An annular flume was used to simulate riverine bedform motion, examining the suspension and infiltration of denser-than-water microplastic particles, including polyvinyl chloride (PVC), polyamide (PA), and polylactide (PLA). The experiments focused on various particle sizes (ranging from 0.2 to 5 mm in diameter) and bedform migration speeds, known as celerities. The findings indicate that particle size is a significant factor influencing the depth of infiltration and distribution within sediment layers, whereas the impact of bedform celerities and particle densities appears less significant. This research provides novel insights into the behavior of microplastics in dynamic sedimentary environments, highlighting the intricate interaction between microplastic characteristics and sedimentary processes. The results contribute to an enhanced understanding of microplastic distribution and accumulation in riverine systems, offering crucial data for developing predictive models and formulating potential remediation strategies for microplastic pollution.

Planning target volume margin in head and neck cancer patients undergoing radiation therapy: Estimations derived from own data and literature.

Planning target volume (PTV) to deliver the desired dose to the clinical target volume (CTV) accounts for systematic (∑) and random (σ) errors during the planning and execution of intensity modulated radiation therapy (IMRT). As these errors vary at different departments, this study was conducted to determine the 3-dimensional PTV (PTV3D) margins for head and neck cancer (HNC) at our center. The same was also estimated from reported studies for a comparative assessment. A total of 77 patients with HNCs undergoing IMRT were included. Of these, 39 patients received radical RT and 38 received postoperative IMRT. An extended no action level protocol was implemented using on-board imaging. Shifts in the mediolateral (ML), anteroposterior (AP), and superoinferior (SI) directions of each patient were recorded for every fraction. PTV margins in each direction (ML, AP, SI) and PTV3D were calculated using van Herk's equation. Weighted PTV3D was also computed from the ∑ and σ errors in each direction published in the literature for HNC. Our patients were staged T2-4 (66/77) and N0 (39/77). In all, 2280 on-board images were acquired, and daily shifts in each direction were recorded. The PTV margins in the ML, AP, and SI directions were computed as 3.2 mm, 2.9 mm, and 2.6 mm, respectively. The PTV3D margin was estimated to be 6.5 mm. This compared well with the weighted median PTV3D of 7.2 mm (range: 3.2 to 9.9) computed from the 16 studies reported in the literature. To ensure ≥95% CTV dose coverage in 90% of HNC patients, PTV3D margin for our department was estimated as 6.5 mm. This agrees with the weighted median PTV3D margin of 7.2 mm computed from the 16 published studies in HNCs. Site-specific PTV3D margin estimations should be an integral component of the quality assurance protocol of each department to ensure adequate coverage of dose to CTV during IMRT.

Orthodontic treatment and biological limits: a retrospective clinical trial.

BACKGROUND: The fundamental part of every successful orthodontic treatment is the detailed treatment planning including a precise determination of the virtual treatment objective (VTO) while considering the biological and anatomical limits. The aim of this study is to investigate and to compare the feasibility of the established reference values before and after orthodontic treatment and to determine the usefulness of this parameters as guidance for the sagittal anterior, sagittal posterior and transverse biological boundaries. MATERIALS AND METHODS: Thirty-two patients aged 9 to 18 years (12 male and 20 female) with all permanent teeth present were randomly selected for orthodontic treatment with fixed multibracket appliance regardless of the potential malocclusion. The parameters 6-PTV, 1-NB [mm] and the WALA ridge were set for the identification of the transverse, sagittal anterior and sagittal posterior tooth position. The measurements were carried out at the beginning (T0) and at the end (T1) of the orthodontic treatment. They were set in relation with their individual threshold values (G). After the results of the measurements were conducted using the software OnyxCeph3TM (version 3.2.185 (505), Image Instruments GmbH, Chemnitz, DE), they were statistically calculated in the software RStudio (2022.12.0 Build 353 © 2009-2022 Posit Software PBC). RESULTS: Among the 32 patients, the mean pre- and post-treatment changes measured through the three parameters in relation to the individual reference values were statistically significant (p < 0.01). The mean values for 6-PTV, 1-NB and the WALA ridge amounted 15.37 mm, 2.56 mm and 4.23 mm at the beginning of the treatment, while after the treatment the measured values amounted 20.31 mm, 2.4 mm and 5.55 mm. These measurements combined with the statistical analysis of the changes of WALA ridge (T0, T1) confirmed that the teeth have been successfully uprighted and aligned. Furthermore, the maxillary first molars have been moved slightly mesially, as proven by the changes in 6-PTV, without certainty as to whether bodily movement or mesial tipping took place. Additionally, the lower incisors have been protruded, slightly exceeding the individual threshold values. CONCLUSION: The parameters investigated provide a suitable assessment tool for recording the limits of the sagittal posterior, the sagittal anterior and the transverse dimension.

A feasibility study of adaptive radiation therapy for postprostatectomy prostate cancer.

Postoperative prostate radiotherapy requires large planning target volume (PTV) margins to account for motion and deformation of the prostate bed. Adaptive radiation therapy (ART) can incorporate image-guidance data to personalize PTVs that maintain coverage while reducing toxicity. We present feasibility and dosimetry results of a prospective study of postprostatectomy ART. Twenty-one patients were treated with single-adaptation ART. Conventional treatments were delivered for fractions 1 to 6 and adapted plans for the remaining 27 fractions. Clinical target volumes (CTVs) and small bowel delineated on fraction 1 to 4 CBCT were used to generate adapted PTVs and planning organ-at-risk (OAR) volumes for adapted plans. PTV volume and OAR dose were compared between ART and conventional using Wilcoxon signed-rank tests. Weekly CBCT were used to assess the fraction of CTV covered by PTV, CTV D99, and small bowel D1cc. Clinical metrics were compared using a Student's t-test (p < 0.05 significant). Offline adaptive planning required 1.9 ± 0.4 days (mean ± SD). ART decreased mean adapted PTV volume 61 ± 37 cc and bladder wall D50 compared with conventional treatment (p < 0.01). The CTV was fully covered for 96% (97%) of fractions with ART (conventional). Reconstructing dose on weekly CBCT, a nonsignificant reduction in CTV D99 was observed with ART (94%) compared to conventional (96%). Reduced CTV D99 with ART was significantly correlated with large anterior-posterior rectal diameter on simulation CT. ART reduced the number of fractions exceeding our institution's small bowel D1c limit from 14% to 7%. This study has demonstrated the feasibility of offline ART for post-prostatectomy cancer. ART facilitates PTV volume reduction while maintaining reasonable CTV coverage and can reduce the dose to adjacent normal tissues.

Seizure outcomes following single-fraction versus hypofractionated radiosurgery for brain metastases: a single-center experience.

OBJECTIVE: Although seizures are a relatively common phenomenon in the setting of brain metastases (BMs), there are no discrete recommendations regarding the use of antiepileptic drugs (AEDs) in this population, either in general or in the context of treatment. The authors' aim was to better understand the underlying pathological factors as well as the therapeutic techniques that may lead to seizures following the radiosurgical treatment of BMs with the goal of guiding appropriate AED prophylaxis. METHODS: Adult patients with BMs diagnosed from 2013 to 2020 at a single academic institution and treated with radiation therapy were included in this study. The authors evaluated factors associated with the incidence of seizures throughout the disease course, with a focus on seizures in the 90-day period following stereotactic radiosurgery (SRS). RESULTS: Four hundred forty-four patients with newly diagnosed BMs were identified, 10% of whom had seizures at the time of presentation and 28% of whom had a seizure at any point during the study period. Tumor histology was significantly associated with initial seizure risk. AED use was highly variable. In the 90-day post-SRS period, the summed total planning target volume (PTV) was independently predictive of post-SRS seizures, regardless of the fractionation scheme (single fraction vs hypofractionated) and other clinical factors. The number of supratentorial BMs was not predictive of post-SRS seizures. CONCLUSIONS: PTV is a superior predictor of post-SRS seizures relative to the number of supratentorial BMs, as it serves as a volumetric proxy for intracranial disease burden. A larger PTV, alongside tumor histology and prior seizure history, should be considered in the decision-making process for AED use following radiosurgery.

Remarkable N2 selectivity enhancement of NH3-SCO reactions over V0.5/Pt0.04/TiO2 catalyst through Cu-Er co-modification.

Pt-V bimetallic catalysts maybe promising substitutes to precious metal catalysts for selective catalytic oxidation (SCO) of NH3. But it remains a major challenge for Pt-V bimetallic catalysts to pursue high NH3 conversion rate and N2 selectivity simultaneously. In this work, both Cu and Er were adopted to modify V0.5/Pt0.04/TiO2 catalyst (denoted as V/PT), and the influences of Cu and Er doping amounts on NH3-SCO performance of V/PT catalysts were investigated systematically. The results indicated that the co-modification of Cu and Er imposed little influence on NH3 conversion efficiency, but significantly boosted N2 selectivity. Compared with other Cu-Er-modified V/PT catalysts, CEV/PT-4 catalyst exhibited outstanding NH3-SCO performance, which attained completely 100% NH3 conversion efficiency and > 90% N2 selectivity in the temperature range of 225-450 °C. It was significantly superior to the NH3-SCO performance of most previously reported catalysts. The characterization results indicated that the adequate doping amounts of Cu and Er resulted in an obvious enhancement on redox property and surface acidity of CEV/PT-4 catalyst. It also led to abundant Pt0 and surface chemisorbed oxygen species on catalyst surface, which facilitated the oxidation of NH3 to NOx and enhanced i-SCR reactions. In situ DRIFTS results showed that -NH2 species on the surface of CEV/PT-4 catalyst could actively react with nitrate species to generate N2 and H2O.

Evaluation of PTV margins and plan robustness for single isocentre multiple target stereotactic radiosurgery.

PURPOSE: Robustness to residual setup errors and linac delivery errors of BrainLab Elements single-isocentre-multiple-target stereotactic radiosurgery was evaluated. METHODS: Residual setup errors of 13 patients were evaluated. Linac delivery error was quantified through multi-metastases-Winston-Lutz measurements. PTV margins were calculated using the van Herk recipe. Patient scans were translated and rotated by the median and 95th percentile of the combined uncertainties, and plans were recalculated subsequently. Previous patients' plans were then replanned with the derived margins, effects on GTV coverage and normal brain doses were assessed. RESULTS: Mean (±stdev) coverage of all targets in the original plans were 99.4% (±0.9%) and 98.9% (±1.0%) for 1 and 3-fraction patients respectively. Median geometrical errors did not result in significant differences. A statistically significant reduction in coverage to 91.4% (±10.4%) and 93.0% (±9.6%) was seen under 95th percentile errors. Applying the derived optimal margin of 0.5 mm resulted in 78% of the GTVs retaining a coverage of 98% or above even in the presence of 95th percentile errors, compared to only 30% if no margins were applied. Replanning with margins also caused no significant increase to local normal brain doses, however global dose increases varied according to the number of metastases. CONCLUSIONS: Plans were shown to be robust to average geometrical uncertainties despite targets having no margins, however occurrence of GTV under-coverage increased under 95th percentile scenarios. The margin was proven to substantially improve the target dose coverage with limited change to local normal brain doses, although not all sources of geometrical uncertainty were considered.

[Movement of a fluvial particle under the influence of coherent structures]. / Bewegung eines Einzelkorns unter dem Einfluss kohärenter Strukturen.

In a fundamental study the influence of coherent structures on the incipient motion of single fluvial grain was experimentally investigated. To fully characterize coherent structures, the three-dimensional velocity field must be known with high temporal resolution. Using a tr-3D PTV system (tr = time-resolved, PTV = particle tracking velocimetry) this could be achieved. The influence of hairpin vortices and counter-rotating longitudinal vortices (VLSM) on sediment transport has been postulated in several studies, but due to the missing 3D information, evidence has been lacking. In the present "Rolling Stones test series", the incipient motion of a single grain was investigated for smooth and rough beds. It could be shown for the first time that both hairpin vortices and VLSM trigger particle entrainment. Hairpin vortices could also be detected on rough beds, contrary to common hypotheses, and triggered particle movement. The long-term study should also find practical applications in the coming years and increase the accuracy of sediment transport calculations in rivers.

[Experimental and numerical investigation of fluid-particle-interactions in water]. / Experimentelle und numerische Untersuchung von Fluid-Partikel-Interaktionen in Wasser.

For the development of improved sediment transport models, the basic understanding of the interaction between the solid particle and the moving fluid (water) is important. In this article, current developments in the field of fluid-particle interaction are presented based on two research articles by Gold et al. (2023) and Worf et al. (2022). One presented in this article uses state of the art measurement methods to investigate the flow around spheres of different densities that oscillate in initially resting body of water. For the spherical pendulum a similar vortex shedding characteristic was observed for all investigated fluid density ratios (m*=ρS/ρF=1.14,14.95, density ratio between solid and fluid). A new object tracking method (DOT) is also presented, which enables temporally and spatially resolved analysis of flow structures in the fluid field. The experimental results of Gold et al. (2023) show, that vortex shedding occurs during the first period. This vortex propagates downward and eventually dissipates. Furthermore, a damping optimum of the spherical pendulum in the range of m*=2.50 was observed. Additionally, an experiment with a cylindrical pendulum with m∗=4.98 was investigated numerically utilizing an immersed boundary method. The process of creation and separation up to the dissipation of a vortex ring was described. Furthermore, this investigation by Worf et al. (2022) described the creation of tip vortices. These were connected with the development of the three-dimensional flow and added mass coefficient.

Planning strategies for robust carbon-ion scanning radiotherapy for stage I esophageal cancer: a retrospective study.

This study aimed to establish a treatment planning strategy with carbon-ion scanning radiotherapy (CIRTs) for stage I esophageal cancer. The clinical data of seven patients treated with CIRTs were used. The setup error and interfractional and intrafractional motion error were analyzed using in-room computed tomography (CT) images for each treatment day. Finally, the planning target volume (PTV) margin was identified according to the accuracy of the treatment system. To ensure robustness against the positional displacements of the target and organs at risk (OAR), the replacement areas were placed as a contour adjacent to the tumor or OAR on the CT-image. The CT values of these areas were replaced by those of the target or OAR. Further, the dose distributions were optimized. Moreover, the variations in the target coverage from the initial plan for each treatment day (ΔV95%) were evaluated. By contrast, the risk of OAR was not evaluated in this study. The setup error was within 1.0 mm. The interfractional and intrafractional target motion errors were 2.8 and 5.0 mm, respectively. The PTV margins were 6.5 and 6.8 mm in the axial and depth directions, respectively. The robustness to target and OAR displacement was evaluated. The results showed that the target coverage with replacement could suppress decreased target coverage more than that without replacement. The PTV determination and replacement methods used in this study improved the target coverage in CIRTs for stage I esophageal cancer. Despite the need for a clinical follow-up, this method may help to improve clinical outcomes.

Characterization of Mechanical and Cellular Effects of Rhythmic Vertical Vibrations on Adherent Cell Cultures.

This paper presents an innovative experimental setup that employs the principles of audio technology to subject adherent cells to rhythmic vertical vibrations. We employ a novel approach that combines three-axis acceleration measurements and particle tracking velocimetry to evaluate the setup's performance. This allows us to estimate crucial parameters such as root mean square acceleration, fluid flow patterns, and shear stress generated within the cell culture wells when subjected to various vibration types. The experimental conditions consisted of four vibrational modes: No Vibration, Continuous Vibration, Regular Pulse, and Variable Pulse. To evaluate the effects on cells, we utilized fluorescence microscopy and a customized feature extraction algorithm to analyze the F-actin filament structures. Our findings indicate a consistent trend across all vibrated cell cultures, revealing a reduction in size and altered orientation (2D angle) of the filaments. Furthermore, we observed cell accumulations in the G1 cell cycle phase in cells treated with Continuous Vibration and Regular Pulse. Our results demonstrate a negative correlation between the magnitude of mechanical stimuli and the size of F-actin filaments, as well as a positive correlation with the accumulations of cells in the G1 phase of the cell cycle. By unraveling these analyses, this study paves the way for future investigations and provides a compelling framework for comprehending the intricate cellular responses to rhythmic mechanical stimulation.

Outcomes following therapeutic intervention of post-traumatic vasospasm: A systematic review and meta-analysis.

BACKGROUND: Vasospasm occurrence following traumatic brain injury may impact neurologic and functional recovery of patients, yet treatment of post-traumatic vasospasm (PTV) has not been well documented. This systematic review and meta-analysis aims to assess the current evidence regarding favorable outcome as measured by Glasgow Outcome Scale (GOS) scores following treatment of PTV. METHODS: A systematic review of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included manuscripts were methodically scrutinized for quality; occurrence of PTV; rate of favorable outcome following each treatment modality; and follow-up duration. Treatments evaluated were calcium channel blockers (CCBs), endovascular intervention, and dopamine-induced hypertension. Outcomes were compared via the random-effects analysis. RESULTS: Fourteen studies with 1885 PTV patients were quantitatively analyzed: 982 patients who received tailored therapeutic intervention and 903 patients who did not receive tailored therapy. For patients undergoing treatment, the rate of favorable outcome was 57.3 % (500/872 patients; 95 % CI 54.1 - 60.6 %) following administration of CCBs, 94.1 % (16/17 patients; 95 % CI 82.9 - 100.0 %) following endovascular intervention, and 54.8 % (51/93 patients; 95 % CI 44.7 - 65.0 %) following dopamine-induced hypertension. Of note, the endovascular group had the highest rate of favorable outcome but was also the smallest sample size (n = 17). Patients who received tailored therapeutic intervention for PTV had a higher rate of favorable outcome than patients who did not receive tailored therapy: 57.7 % (567/982 patients; 95 % CI 54.1 - 60.8 %) versus 52.0 % (470/903 patients; 95 % CI 48.8 - 55.3 %), respectively. CONCLUSIONS: The available data suggests that tailored therapeutic intervention of PTV results in a favorable outcome. While endovascular intervention of PTV had the highest rate of favorable outcome, both CCB administration and dopamine-induced hypertension had similar lower rates of favorable outcome.

Robust VMAT treatment planning for extremity soft tissue sarcomas.

Volumetric modulated arc therapy (VMAT) is a frequently employed and guideline-recommended radiotherapy (RT) modality for extremity soft tissue sarcomas (eSTS). Prior studies have demonstrated that significant tumor volume changes during treatment result in loss of target volume coverage with highly conformal techniques such as VMAT, but few solutions exist to these issues aside from adaptive replanning. Here, we describe a related but novel phenomenon in which relatively minor changes in surface volume contour (whether due to daily setup uncertainty, edema of peritumoral tissue, or progression or pseudo-progression of tumor volume itself) can result in unexpected subcutaneous hotspots. This phenomenon is of significant clinical concern given the known association between skin dose and major wound complications during preoperative RT for eSTS. By evaluating daily cone-beam CT (CBCT) images from thirteen eSTS patients treated with VMAT RT, we identify daily surface contour changes (range: 2 mm-15 mm, median: 8 mm) which are frequently below conventional adaptive replanning thresholds. When applied under experimental conditions, these external contour changes did not have major impacts on target volume coverage (range: 30.2%-91.2%, mean: 72.5%) but did result in unexpected hotspots of 125.8% on average (range: 110.0%-142.2%) in the subcutaneous tissues. To mitigate this issue, we develop a methodology for VMAT treatment planning using flash PTV and virtual bolus (VB) to produce robust treatment plans that are more resistant to target volume changes, surface contour changes, and setup uncertainties than conventional planning methods. With this methodology, robust plans were equivalent to standard plans at baseline, but, after incorporation of surface volume changes, both maintained target volume coverage (p < 0.001) and prevented development of subcutaneous hotspots (p < 0.001) better than standard plans. As such, this treatment planning methodology may facilitate development of robust VMAT treatment plans that minimize development of subcutaneous hotspots and preserve target volume coverage in the context of routine volumetric changes during preoperative RT.

Reducing the margin in prostate radiotherapy: optimizing radiotherapy with a general-purpose linear accelerator using an in-house position monitoring system.

Purpose: To study the feasibility of optimizing the Clinical Target Volume to Planning Target Volume (CTV-PTV) margin in prostate radiotherapy(RT) with a general-purpose linear accelerator using an in-house developed position monitoring system, SeedTracker. Methods: A cohort of 30 patients having definitive prostate radiotherapy treated within an ethics-approved prospective trial was considered for this study. The intrafraction prostate motion and the position deviations were measured using SeedTracker system during each treatment fraction. Using this data the CTV-PTV margin required to cover 90% of the patients with a minimum of 95% of the prescription dose to CTV was calculated using van Herk's formula. The margin calculations were performed for treatment scenarios both with and without applying the position corrections for observed position deviations. The feasibility of margin reduction with real-time monitoring was studied by assessing the delivered dose that incorporates the actual target position during treatment delivery and comparing it with the planned dose. This assessment was performed for plans generated with reduced CTV-PTV margin in the range of 7mm-3mm. Results: With real-time monitoring and position corrections applied the margin of 2.0mm, 2.1mm and 2.1mm in LR, AP and SI directions were required to meet the criteria of 90% population to receive 95% of the dose prescription to CTV. Without position corrections applied for observed position deviations a margin of 3.1mm, 4.0mm and 3.0mm was required in LR, AP and SI directions to meet the same criteria. A mean ± SD reduction of 0.5 ± 1.8% and 3 ± 7% of V60 for the rectum and bladder can be achieved for every 1mm reduction of PTV margin. With position corrections applied, the CTV D99 can be delivered within -0.2 ± 0.3 Gy of the planned dose for plans with a 3mm margin. Without applying corrections for position deviations the CTV D99 was reduced by a maximum of 1.1 ± 1.1 Gy for the 3mm margin plan and there was a statistically significant difference between planned and delivered dose for 3mm and 4mm margin plans. Conclusion: This study demonstrates the feasibility of reducing the margin in prostate radiotherapy with SeedTracker system without compromising the dose delivery accuracy to CTV while reducing dose to critical structures.

Cine MRI-based analysis of intrafractional motion in radiation treatment planning of head and neck cancer patients.

PURPOSE/OBJECTIVE(S): To investigate intrafraction motion of (HN) target volumes and to determine patient-specific planning target volume (PTV) margins. MATERIALS/METHODS: MR-cine imaging was performed for radiation treatment planning in HN cancer patients treated with definitive EBRT (n = 62) or SBRT (n = 4) on a 1.5 T MRI between 2017-2019. Dynamic MRI scans (sagittal orientation, 2 × 82 × 7 mm3 resolution), ranging from 3-5 min and 900-1500 images, were acquired. The position of the maximum tumor displacement along each direction in the anterior/posterior (A/P) and superior/inferior (S/I) position was recorded and analyzed to determine average PTV margins. RESULTS: Primary tumor sites (n = 66) were oropharynx (n = 39), larynx (n = 24) and hypopharynx (n = 3). PTV margins for A/P/S/I positions were 4.1/4.4/5.0/6.2 mm and 4.9/4.3/6.7/7.7 mm for oropharyngeal and laryngeal/hypopharyngeal cancers when accounting for all motion. V100 for PTV was calculated and compared to the original plans. The mean drop in PTV coverage was in most cases under 5%. For a subset of patients with 3 mm plans available, V100 for PTV had more substantial decreases in coverage averaging 8.2% - and 14.3% for oropharyngeal and laryngeal/hypopharynx plans, respectively. CONCLUSION: The use of MR-cine in treatment planning allows for quantification of tumor motion during swallow and resting periods and should be accounted for during treatment planning. With motion considered, the derived margins may exceed the commonly used 3-5 mm PTV margins. Quantification and analysis of tumor and patient-specific PTV margins is a step towards real-time MRI guidance adaptive radiotherapy.

Assessment of PTV margin adequacy for single isocenter multiple brain metastases using genetic algorithms.

Purpose. To study the impact on dose coverage and the dose to the healthy tissue applying optimized margins in single isocenter multiple brain metastases radiosurgery (SIMM-SRS) in linac machine based on setup rotations/translations induced errors calculated by a genetic algorithm (GA).Method.The following quality indices of SIMM-SRS were analyzed for 32 plans (256 lesions): Paddick conformity index (PCI), gradient index (GI), maximum (Dmax) and mean (Dmean) doses, local and global V12for the healthy brain. A GA based on Python packages were used to determine the maximum shift produced by induced errors of 0.2°/0.2 mm, and 0.5°/0.5 mm in 6 degrees of freedom.Results.In terms of Dmax, and Dmean, the quality of the optimized-margin plans remains unchanged (p > 0.072) concerning the original plan. However, considering the 0.5°/0.5 mm plans, PCI and GI decreased for ≥10 metastases, and local, and global V12increased considerably in all cases. To consider 0.2°/0.2 mm plans, PCI and GI get worse but local, and global V12improved in all cases.Conclusion.GA facilities to find the individualized margins automatically among the number of possible permutations of the setup order. The user-dependent margins are avoided. This computational approach takes into account more SRS sources of uncertainty, enabling the protection of the healthy brain by 'smartly' reducing the margins, and maintaining clinically acceptable target volumes' coverage in most cases.

Assessing the impact of intrafraction motion correction on PTV margins and target and OAR dosimetry for single-fraction free-breathing lung stereotactic body radiation therapy.

The objective of this research is to investigate intrafraction motion correction on planning target volume (PTV) margin requirements and target and organ-at-risk (OAR) dosimetry in single-fraction lung stereotactic body radiation therapy (SBRT). Sixteen patients (15 with upper lobe lesions, 1 with a middle lobe lesion) were treated with single-fraction lung SBRT. Cone-beam computed tomography (CBCT) images were acquired before the treatment, between the arcs, and after the delivery of the treatment fraction. Shifts from the reference images were recorded in anterior-posterior (AP), superior-inferior (SI), and lateral (LAT) dimensions. The deviations from the reference image were calculated for 3 clinical scenarios: not applying intratreatment couch shifts and not correcting for pretreatment deviations < 3 mm ( scenario 1), not applying intratreatment couch shifts and correcting for pretreatment deviations < 3 mm ( scenario 2), and applying all pre- and intratreatment couch shifts (scenario 3). PTV margins were determined using the van Herk formalism for each scenario and maximum and average deviations were assessed. The clinical scenarios were modelled in the treatment planning system based on each patient dataset to assess target and OAR dosimetry. Calculated lower-bound PTV margins in the AP, SI, and LAT dimensions were [4.6, 3.5, 2.3] mm in scenario 1, [4.6, 2.4, 2.2] mm in scenario 2, and [1.7, 1.2, 1.0] mm in scenario 3. The margins are lower bounds because they do not include contributions from nonmotion related errors. Average and maximum intrafraction deviations were larger in the AP dimension compared to the SI and LAT dimensions for all scenarios. A unidimensional movement (several mm) in the negative AP dimension was observed in clinical scenarios 1 and 2 but not scenario 3. Average intrafraction deviation vectors were 1.2, 1.1, and 0.3 mm for scenarios 1, 2, and 3, respectively. Modelled clinical scenarios revealed that using scenario 3 yields significantly fewer treatment plan objective failures compared to scenarios 1 and 2 using a Wilcoxon signed-rank test. Intratreatment motion correction between each arc may enable reductions PTV margin requirements. It may also compensate for unidimensional negative AP movement, and improve target and OAR dosimetry.

Development of a PTV margin for preclinical irradiation of orthotopic pancreatic tumors derived from a well-known recipe for humans.

In human radiotherapy a safety margin (PTV margin) is essential for successful irradiation and is usually part of clinical treatment planning. In preclinical radiotherapy research with small animals, most uncertainties and inaccuracies are present as well, but according to the literature a margin is used only scarcely. In addition, there is only little experience about the appropriate size of the margin, which should carefully be investigated and considered, since sparing of organs at risk or normal tissue is affected. Here we estimate the needed margin for preclinical irradiation by adapting a well-known human margin recipe from van Herck et al. to the dimensions and requirements of the specimen on a small animal radiation research platform (SARRP). We adjusted the factors of the described formula to the specific challenges in an orthotopic pancreatic tumor mouse model to establish an appropriate margin concept. The SARRP was used with its image-guidance irradiation possibility for arc irradiation with a field size of 10 × 10 mm2 for 5 fractions. Our goal was to irradiate the clinical target volume (CTV) of at least 90% of our mice with at least 95% of the prescribed dose. By carefully analyzing all relevant factors we gain a CTV to planning target volume (PTV) margin of 1.5 mm for our preclinical setup. The stated safety margin is strongly dependent on the exact setting of the experiment and has to be adjusted for other experimental settings. The few stated values in literature correspond well to our result. Even if using margins in the preclinical setting might be an additional challenge, we think it is crucial to use them to produce reliable results and improve the efficacy of radiotherapy.