Minimizing human interference in an online fully automated daily adaptive radiotherapy workflow for bladder cancer.

PURPOSE: The aim was to study the potential for an online fully automated daily adaptive radiotherapy (RT) workflow for bladder cancer, employing a focal boost and fiducial markers. The study focused on comparing the geometric and dosimetric aspects between the simulated automated online adaptive RT (oART) workflow and the clinically performed workflow. METHODS: Seventeen patients with muscle-invasive bladder cancer were treated with daily Cone Beam CT (CBCT)-guided oART. The bladder and pelvic lymph nodes (CTVelective) received a total dose of 40 Gy in 20 fractions and the tumor bed received an additional simultaneously integrated boost (SIB) of 15 Gy (CTVboost). During the online sessions a CBCT was acquired and used as input for the AI-network to automatically delineate the bladder and rectum, i.e. influencers. These influencers were employed to guide the algorithm utilized in the delineation process of the target. Manual adjustments to the generated contours are common during this clinical workflow prior to plan reoptimization and RT delivery. To study the potential for an online fully automated workflow, the oART workflow was repeated in a simulation environment without manual adjustments. A comparison was made between the clinical and automatic contours and between the treatment plans optimized on these clinical (Dclin) and automatic contours (Dauto). RESULTS: The bladder and rectum delineated by the AI-network differed from the clinical contours with a median Dice Similarity Coefficient of 0.99 and 0.92, a Mean Distance to Agreement of 1.9 mm and 1.3 mm and a relative volume of 100% and 95%, respectively. For the CTVboost these differences were larger, namely 0.71, 7 mm and 78%. For the CTVboost the median target coverage was 0.42% lower for Dauto compared to Dclin. For CTVelective this difference was 0.03%. The target coverage of Dauto met the clinical requirement of the CTV-coverage in 65% of the sessions for CTVboost and 95% of the sessions for the CTVelective. CONCLUSIONS: While an online fully automated daily adaptive RT workflow shows promise for bladder treatment, its complexity becomes apparent when incorporating a focal boost, necessitating manual checks to prevent potential underdosage of the target.

How Accurate Is Frameless Fiducial-Free Deep Brain Stimulation?

BACKGROUND AND OBJECTIVES: Frameless deep brain stimulation (DBS) offers advantages in terms of patient comfort and reduced operative time. However, the need for bony fiducial markers for localization remains a drawback due to the time-consuming and uncomfortable procedure. An alternative localization method involves the direct tracking of an intraoperative 3-dimensional scanner. This study aims to assess the accuracy of the NexFrame frameless DBS system in conjunction with the O-Arm (Medtronic Inc.), both with and without fiducial markers. METHODS: The locations of 100 DBS leads were determined, with 50 cases using fiducial-free localization and 50 involving fiducial markers. The coordinates were compared with the expected intraoperative targets. Absolute errors in the X, Y, and Z coordinates (ΔX, ΔY, and ΔZ) were calculated, along with the vector error (Euclidean) (vector error ). RESULTS: The vector error averaged 1.61 ± 0.49 mm (right) and 1.52 ± 0.60 mm (left) for the group without fiducial bone markers and 1.66 ± 0.69 (right) and 1.44 ± 0.65 mm (left) for the other cohort (P = .76 right; P = .67 left). Absolute errors in the X, Y, and Z coordinates for the fiducial-free group were 0.88 ± 0.55, 0.79 ± 0.45, and 0.79 ± 0.57 mm (right) and 0.72 ± 0.37, 0.78 ± 0.56, and 0.77 ± 0.71 mm (left). For the group with fiducial markers, these errors were 0.87 ± 0.72, 0.92 ± 0.39, and 0.86 ± 0.50 mm (right) and 0.75 ± 0.33, 0.80 ± 0.51, and 0.73 ± 0.64 mm (left) with no statistically significant difference. CONCLUSION: Our analysis of the accuracy of NexFrame DBS, both with and without fiducial markers, using an intraoperative navigable cone-beam computed tomography, demonstrates that both techniques provide sufficient and equivalent 3-dimensional accuracy.

The impact of mandibular partial edentulous distal extension on virtual occlusal record accuracy when using two different intraoral scanners: An in vitro analysis.

OBJECTIVES: This in vitro study was formulated to clarify how mandibular partial edentulous distal extension involving three missing teeth affects the virtual occlusal record (VOR) accuracy, in terms of both trueness and precision, when using two different intraoral scanners (IOSs) - the Primescan (PS) and Trios 4 (TR) scanners. METHODS: A typodont model missing the left mandibular second premolar, first molar, and second molar as well as the right mandibular first molar was mounted on a semi-adjustable articulator. Four implants were placed at the sites of the missing mandibular teeth. Six pairs of stainless steel markers (diameter: 0.5 mm) were affixed to the maxillary and mandibular casts in the buccal gingiva adjacent to the implants and on the facial surfaces of teeth as reference positions for measurements. The model was digitized with an inEox X5 laboratory scanner to create a reference dataset. Intraoral scans were performed with the PS and TR scanners, with each scan duplicated 10 times to generate 20 paired IOS files. Automatic VOR generation followed the bilateral buccal scan protocol, divided into PS and TR groups (n = 10). Six subgroups of linear distances between interarch markers were assessed with Geomagic Control software, comparing deviations from the reference scan. Data normality was confirmed with the Shapiro-Wilk test. Trueness was evaluated with two-way ANOVAs and pairwise comparisons performed with Tukey's test, whereas precision was assessed with the Levene test (α=0.05). RESULTS: The mean linear deviation (Δd) and standard deviation (SD) of VOR were both significantly affected by marker position (P < 0.001), and a significant position × scanner interaction was detected (P < 0.001). Negative mean deviations were observed for the distally extended edentulous areas in both groups. PS scans exhibited trueness that was significantly better than that for TR scans in the D16-46, D13-43, D23-33, and D27-37 subgroups (P < 0.05), whereas there were no significant differences in the D25-35 or D26-36 subgroups. PS scanning was associated with significantly better precision than TR scanning (P < 0.001), and worse precision was observed at D27-37 for both tested IOSs. CONCLUSIONS: Mandibular partial edentulous distal extension can significantly affect VOR accuracy. The type of IOS could also affect VOR accuracy depending on the area being scanned, with better overall performance observed for the Primescan device as compared to the Trios 4 scanner. Both of these IOSs tended to underestimate VOR occlusal dimensions in mandibular distally extended edentulous areas. CLINICAL SIGNIFICANCE: Mandibular distal edentulous areas can contribute to occlusal dimensions that are underestimated in digital workflows, which may result in infraocclusal discrepancies that arise when performing restorations. IOSs and VOR scanning protocols should thus be carefully considered in order to minimize these risks.

CT-Guided Fiducial Marker Implantation with Ultra-fine 25-Gauge Needle Prior to Proton Therapy for Liver Malignancies.

PURPOSE: Proton therapy is highly effective for liver malignancies, and to increase its accuracy, placement of fiducial markers in the liver is preferred. We retrospectively evaluated the safety and feasibility of CT-guided fiducial marker implantation using ultra-fine 25-gauge needles before proton therapy for liver malignancies. MATERIALS AND METHODS: Between May 2016 and April 2021, 334 cases were investigated. All of procedures were performed without anesthesia. Technical success was defined as the completion of implantation at the intended site. Tumor-marker distance and possibility of synchronization between tumors and markers were evaluated and compared with Mann-Whitney U test. Complications were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Technical success rate was 97.3%. Tumor-marker distance was 19.1 mm (median, range 0-96) in the group in which the implanted marker was synchronized with tumor (n = 315), while it was 34.5 mm (median, range 6-94) in the group in which the implanted marker was not synchronized (n = 13) (p value = 0.011 < 0.05). The complication rate was 2.4%, 2 were classified as grade 4 and 5 as grade 1, and 1 as grade 2. There were no grade 3 or higher complications that seemed to be related to the procedure. CONCLUSION: CT-guided marker implantation using a 25-gauge needle achieved a satisfactory success rate with few complications and was useful for the image-guided and respiratory-synchronized proton therapy. LEVEL OF EVIDENCE 3: Local non-random sample.

Accuracy of dynamic computer-assisted implant surgery in fully edentulous patients: An in vitro study.

OBJECTIVES: To compare miniscrew versus bone tracing registration methods on dental implant placement accuracy and time efficiency in edentulous jaws using a dynamic computer-assisted implant surgery (d-CAIS) system. METHODS: Twelve fully edentulous maxillary models were allocated into two groups: miniscrew tracing (MST) group, where registration was performed by tracing four miniscrews; and bone tracing (BT) group, where registration was conducted by tracing maxillary bone fiducial landmarks. Six implants were placed on each model using the X-Guide® d-CAIS system. Pre- and postoperative cone-beam computed tomography (CBCT) scans were superimposed to evaluate implant placement accuracy. The time required for registration and the overall surgery time were also recorded. RESULTS: Thirty-six implants were placed in each group. The MST group showed significantly lower mean angulation deviations (mean difference (MD): -3.33°; 95 % confidence interval (CI): -6.56 to -0.09); p = 0.044), 3D platform deviations (MD: -1.01 mm; 95 % CI: -1.74 to -0.29; p = 0.006), 2D platform deviations (MD: -0.97 mm; 95 % CI: -1.71 to -0.23; p = 0.010), and 3D apex deviations (MD: -1.18 mm; 95 % CI: -1.92 to -0.44; p = 0.002) versus the BT group. The overall surgery time was similar for both groups (MD: 6.10 min.; 95 % CI: -0.31 to 12.51; p = 0.06), though bone tracing required significantly more time compared with miniscrew registration (MD: 4.79 min.; 95 % CI: 2.96 to 6.62; p < 0.05). CONCLUSIONS: Registration with MST increases the accuracy of implant placement with a d-CAIS system in edentulous jaws compared with the BT method, and slightly reduces the overall surgery time. CLINICAL SIGNIFICANCE: Miniscrew tracing registration improves implant placement accuracy in comparison with bone tracing registration.

Robust localization of poorly visible tumor in fiducial free stereotactic body radiation therapy.

BACKGROUND AND PURPOSE: Effective respiratory motion management reduces healthy tissue toxicity and ensures sufficient dose delivery to lung cancer cells in pulmonary stereotactic body radiation therapy (SBRT) with high fractional doses. An articulated robotic arm paired with an X-ray imaging system is designed for real-time motion-tracking (RTMT) dose delivery. However, small tumors (<15 mm) or tumors at challenging locations may not be visible in the X-ray images, disqualifying patients with such tumors from RTMT dose delivery unless fiducials are implanted via an invasive procedure. To track these practically invisible lung tumors in SBRT, we hereby develop a deep learning-enabled template-free tracking framework, SAFE Track. METHODS: SAFE Track is a fully supervised framework that trains a generalizable prior for template-free target localization. Two sub-stages are incorporated in SAFE Track, including the initial pretraining on two large-scale medical image datasets (DeepLesion and Node21) followed by fine-tuning on our in-house dataset. A two-stage detector, Faster R-CNN, with a backbone of ResNet50, was selected as our detection network. 94 patients (415 fractions; 40,348 total frames) with low tumor visibility who thus had implanted fiducials were included. The cohort is categorized by the longest dimension of the tumor (<10 mm, 10-15 mm and > 15 mm). The patients were split into training (n = 66) and testing (n = 28) sets. We simulated fiducial-free tumors by removing the fiducials from the X-ray images. We classified the patients into two groups - fiducial implanted inside tumors and implanted outside tumors. To ensure the rigor of our experiment design, we only conducted fiducial removal simulation in training patients and utilized patients with fiducial implanted outside of the tumors for testing. Commercial Xsight Lung Tracking (XLT) and a Deep Match were included for comparison. RESULTS: SAFE Track achieves promising outcomes to as accurate as 1.23±1.32 mm 3D distance in testing patients with tumor size > 15 mm where Deep Match is at 4.75±1.67 mm and XLT is at 12.23±4.58 mm 3D distance. Even for the most challenging tumor size (<10 mm), SAFE Track maintains its robustness at 1.82 plus or minus 1.67 mm 3D distance, where Deep Match is at 5.32 plus or minus 2.32 mm, and XLT is at 24.83±12.95 mm 3D distance. Moreover, SAFE Track can detect some considerably challenging cases where the tumor is almost invisible or overlapped with dense anatomies. CONCLUSION: SAFE Track is a robust, clinically compatible, fiducial-free, and template-free tracking framework that is applicable to patients with small tumors or tumors obscured by overlapped anatomies in SBRT.

The GoldX Fiducial Eraser.

Gold nanoparticles with sizes in the range of 5-15 nm are a standard method of providing fiducial markers to assist with alignment during reconstruction in cryogenic electron tomography. However, due to their high electron density and resulting contrast when compared to standard cellular or biological samples, they introduce artifacts such as streaking in the reconstructed tomograms. Here, we demonstrate a tool that automatically detects these nanoparticles and suppresses them by replacing them with a local background as a post-processing step, providing a cleaner tomogram without removing any sample relevant information or introducing new artifacts or edge effects from uniform density replacements.

Automated fiducial-based alignment of cryo-electron tomography tilt series in Dynamo.

With the advent of modern technologies for cryo-electron tomography (cryo-ET), high-quality tilt series are more rapidly acquired than processed and analyzed. Thus, a robust and fast-automated alignment for batch processing in cryo-ET is needed. While different software packages have made available several approaches for automated marker-based alignment of tilt series, manual user intervention remains necessary for many datasets, thus preventing high-throughput tomography. We have developed a MATLAB-based framework integrated into the Dynamo software package for automatic detection of fiducial markers that generates a robust alignment model with minimal input parameters. This approach allows high-throughput, unsupervised volume reconstruction. This new module extends Dynamo with a large repertory of tools for tomographic alignment and reconstruction, as well as specific visualization browsers to rapidly assess the biological relevance of the dataset. Our approach has been successfully tested on a broad range of datasets that include diverse biological samples and cryo-ET modalities.

Radiomic feature robustness in CT scans affected by fiducial marker induced streak artifacts for patients with hepatocellular carcinoma.

BACKGROUND: Stereotactic body radiation therapy for hepatocellular carcinoma necessitates the implantation of gold fiducial markers in the liver, resulting in artifacts on computed tomography (CT) scans, which affect radiomic feature values. PURPOSE: This report aims to assess the effect of these artifacts on radiomic features and how removing CT slices affects radiomic features extracted from 3D regions of interest (ROI). METHODS: First, the range variation in 38 tumor contours unaffected by artifacts was assessed after sequentially and randomly removing 25%, 50%, 75% of slices. Subsequently, the agreement of feature values before and after removing ROI slices containing artifacts from 186 patients' CT scans was assessed with Lin's concordance correlation coefficient (CCC) and a Wilcoxon signed-rank test. RESULTS: In artifact-free tumor volumes, at least 71% of features remain robust with up to 50% of slices removed, while 56% remains robust with up to 75% of slices removed. When comparing contours before and after removing slices containing artifacts, around a third of features in the tumor contour and surrounding area remain robust (CCC > 0.9), compared to 44% in the healthy liver. Concerning the tumor, 13% (Gray Level Size Zone Matrix) to 61% (first order) of the features remain robust (CCC > 0.9). Over 90% of features differ significantly as assessed by Wilcoxon signed-rank test, however. CONCLUSIONS: This study demonstrates that removing slices containing artifacts is a feasible solution for the CT fiducial problem in this patient population and provides insight into which features are affected.

Magnetic seed localization is feasible for non-palpable melanoma, Merkel cell carcinoma, and soft tissue sarcoma lesions.

BACKGROUND: Localization of non-palpable melanoma, Merkel cell carcinoma (MCC) and soft tissue sarcoma (STS) lesions can be difficult due to size, location, and obesity of patients or fibrosis due to previous treatments. Magnetic seed localization (MSL) is a common method to localize non-palpable breast lesions, but the feasibility of MSL for non-palpable melanoma, MCC and STS lesions has not yet been described. METHODS: In this retrospective single center cohort study, all consecutive patients between January 2021 and October 2023 who had a resection of a non-palpable melanoma, MCC or STS lesion guided by Sirius Pintuition, a MSL technique, were included. The primary endpoint was successful lesion localization during surgery and the secondary endpoints were seed migration, negative resection margins, and complications. RESULTS: Seventy-nine seeds were placed for 76 lesions, which were resected during 68 surgeries in 61 patients. All lesions (100 %) were localized and resected. Median time of surgery was 44 min. No seed migration was observed. A negative resection margin was achieved for 60 (78.9 %) lesions. Clavien Dindo grade ≥2 complications occurred in 7.4 %. CONCLUSION: Magnetic seed localization with Sirius Pintuition is feasible for both non-palpable melanoma, MCC, and STS lesions.

Non-palpable breast lesions localization techniques - A new priority: Results of a Senonetwork survey among breast centers in Italy.

INTRODUCTION: Non palpable breast tumors are increasingly diagnosed because of screening programs, and their localization during surgery is essential to ensure an adequate resection. Little is known regarding which techniques are used in "real world". MATERIALS AND METHODS: A national web-based survey, with a 21-items questionnaire, was conducted among Breast Centers (BCs) in Italy in 2023. RESULTS: Among 153 BCs, 110 (72 %) participated. Wire-guided localization was reported to be the most used technique, regardless of the volume of malignant tumors treated by each Center (N = 36, 33 %). However, newer techniques such as Radioactive occult lesion localization and magnetic seeds, were reported to be employed in 34 (31 %) BCs, and more often among high-volume BCs (>300 cases/year) (N = 32, 29 % vs. N = 13, 12 %; p = 0.02). Logistic problems of localization were reported to cause delays to the scheduled surgery at least once or in multiple occasions in 26 (24 %) and in 4 (3.5 %) BCs, respectively. Although the majority of BCs declared they were satisfied (N = 48, 44 %) or somewhat satisfied (N = 41, 37 %) with the procedure used in their center, responders stated that they would change their technique, or that they were strongly considering this possibility in 24 (22 %) and in 38 (35 %) cases, respectively. The main barrier to introducing a new technique was associated with procedure costs (90 BCs, 82 %). CONCLUSIONS: There are several critical issues regarding localization techniques at a national level. This should be recognized as a priority because of its impact on both patients and clinical practices.

Intrafractional motion and dosimetric analysis in prostate stereotactic body radiation therapy with auto beam hold technique.

Objective: To summarize our institutional prostate stereotactic body radiation therapy (SBRT) experience using auto beam hold (ABH) technique for intrafractional prostate motion and assess ABH tolerance of 10-millimeter (mm) diameter.Approach: Thirty-two patients (160 fractions) treated using ABH technique between 01/2018 and 03/2021 were analyzed. During treatment, kV images were acquired every 20-degree gantry rotation to visualize 3-4 gold fiducials within prostate to track target motion. If the fiducial center fell outside the tolerance circle (diameter = 10 mm), beam was automatically turned off for reimaging and repositioning. Number of beam holds and couch translational movement magnitudes were recorded. Dosimetric differences from intrafractional motion were calculated by shifting planned isocenter.Main Results: Couch movement magnitude (mean ± SD) in vertical, longitudinal and lateral directions were -0.7 ± 2.5, 1.4 ± 2.9 and -0.1 ± 0.9 mm, respectively. For most fractions (77.5%), no correction was necessary. Number of fractions requiring one, two, or three corrections were 15.6%, 5.6% and 1.3%, respectively. Of the 49 corrections, couch shifts greater than 3 mm were seen primarily in the vertical (31%) and longitudinal (39%) directions; corresponding couch shifts greater than 5 mm occurred in 2% and 6% of cases. Dosimetrically, 100% coverage decreased less than 2% for clinical target volume (CTV) (-1 ± 2%) and less than 10% for PTV (-10 ± 6%). Dose to bladder, bowel and urethra tended to increase (Bladder: ΔD10%:184 ± 466 cGy, ΔD40%:139 ± 241 cGy, Bowel: ΔD1 cm3:54 ± 129 cGy; ΔD5 cm3:44 ± 116 cGy, Urethra: ΔD0.03 cm3:1 ± 1%). Doses to the rectum tended to decrease (Rectum: ΔD1 cm3:-206 ± 564 cGy, ΔD10%:-97 ± 426 cGy; ΔD20%:-50 ± 251 cGy).Significance: With the transition from conventionally fractionated intensity modulated radiation therapy to SBRT for localized prostate cancer treatment, it is imperative to ensure that dose delivery is spatially accurate for appropriate coverage to target volumes and limiting dose to surrounding organs. Intrafractional motion monitoring can be achieved using triggered imaging to image fiducial markers and ABH to allow for reimaging and repositioning for excessive motion.

Markerauto2: A fast and robust fully automatic fiducial marker-based tilt series alignment software for electron tomography.

Cryoelectron tomography (cryo-ET) has become an indispensable technology for visualizing in situ biological ultrastructures, where the tilt series alignment is the key step to obtain a high-resolution three-dimensional reconstruction. Specifically, with the advent of high-throughput cryo-ET data collection, there is an increasing demand for high-accuracy and fully automatic tilt series alignment, to enable efficient data processing. Here, we propose Markerauto2, a fast and robust fully automatic software that enables accurate fiducial marker-based tilt series alignment. Markerauto2 implements the following novel pipelines: (1) an accelerated high-precision fiducial marker detection with wavelet multiscale template, (2) an ultra-fast and robust fiducial marker tracking supported by hashed geometric features, (3) a high-angle fiducial marker supplementation strategy to produce more complete tracks, and (4) a precise and robust calibration of projection parameters with group-weighted parameter optimization. Comprehensive experiments conducted on both simulated and real-world datasets demonstrate the robustness, efficiency, and effectiveness of the proposed software.

Test Platform for Developing New Optical Position Tracking Technology towards Improved Head Motion Correction in Magnetic Resonance Imaging.

Optical tracking of head pose via fiducial markers has been proven to enable effective correction of motion artifacts in the brain during magnetic resonance imaging but remains difficult to implement in the clinic due to lengthy calibration and set up times. Advances in deep learning for markerless head pose estimation have yet to be applied to this problem because of the sub-millimetre spatial resolution required for motion correction. In the present work, two optical tracking systems are described for the development and training of a neural network: one marker-based system (a testing platform for measuring ground truth head pose) with high tracking fidelity to act as the training labels, and one markerless deep-learning-based system using images of the markerless head as input to the network. The markerless system has the potential to overcome issues of marker occlusion, insufficient rigid attachment of the marker, lengthy calibration times, and unequal performance across degrees of freedom (DOF), all of which hamper the adoption of marker-based solutions in the clinic. Detail is provided on the development of a custom moiré-enhanced fiducial marker for use as ground truth and on the calibration procedure for both optical tracking systems. Additionally, the development of a synthetic head pose dataset is described for the proof of concept and initial pre-training of a simple convolutional neural network. Results indicate that the ground truth system has been sufficiently calibrated and can track head pose with an error of <1 mm and <1°. Tracking data of a healthy, adult participant are shown. Pre-training results show that the average root-mean-squared error across the 6 DOF is 0.13 and 0.36 (mm or degrees) on a head model included and excluded from the training dataset, respectively. Overall, this work indicates excellent feasibility of the deep-learning-based approach and will enable future work in training and testing on a real dataset in the MRI environment.

Surgical marker navigation system in breast conserving surgery and excision of non-palpable lesions: first Spanish single-center experience.

BACKGROUND: Due to the establishment of screening mammography for breast cancer detection, the number of non-palpable lesions has increased. Thus, an optimal localization system is mandatory for the excision of non-palpable breast tumors. OBJECTIVE: The aim of the study is to report the feasibility Surgical Marker Navigation (SMN) system Sirius Pintuition® for the excision of non-palpable breast tumors and non-palpable axillary lymph nodes. METHODS: A retrospective observational study of patients undergoing breast-conserving surgery and lymph node excision guided by SMN between December 2022 and May 2023 was performed. RESULTS: A total of 84 patients underwent excision of non-palpable breast tumors (77; 91.7%) or non-palpable axillary lymph-nodes (7; 8.3%) using SMN. In total, 94 markers were placed, in 74 patients (88.1%) only one marker was placed, whereas in 10 patients (11.9%) two markers were placed to correctly localize the lesion in the operating room. Most markers were placed using ultrasonographic guidance (69; 82.1%). Seventy-seven patients underwent breast-conserving surgery (91.7%) and 7 (8.3%) lymph node excision. In 10 cases (11.9%), the marker was accidentally displaced during surgery due to the use of magnetized instruments, although the specimen could be removed. In sum, all the markers were removed from the patients, although the marker retrieval rate, as we defined it (percentage of patients in whom the initial excised specimen contained the marker divided by the total number of patients), was 88.1%. CONCLUSION: The use of Sirius Pintuition® SMN for non-palpable breast tumors and non-palpable lymph nodes is feasible, with a retrieval rate of 88.1%.

The influence of radiographic marker registration versus a markerless trace registration method on the implant placement accuracy achieved by dynamic computer-assisted implant surgery. An in-vitro study.

OBJECTIVES: This study aimed to compare the effect the radiographic marker registration (RMR) and markerless tracing registration (MTR) on implant placement accuracy using a dynamic computer-assisted implant surgery system (dCAIS). Additionally, this study aimed to assess the surgical time and whether the implant location influences the accuracy of the two registration methods. METHODS: 136 dental implants were randomly allocated to the RMR or MTR group and were placed with a dCAIS in resin models. Preoperative and postoperative Cone Beam Computer Tomograms (CBCT) were overlaid and implant placement accuracy was assessed. Descriptive and multivariate analysis of the data was performed. RESULTS: Significant differences (P < 0.001) were found for all accuracy variables except angular deviation (RMR:4.30° (SD:4.37°); MTR:3.89° (SD:3.32°)). The RMR had a mean 3D platform deviation of 1.53 mm (SD:0.98 mm) and mean apex 3D deviation of 1.63 mm (SD:1.05 mm) while the MTR had lower values (0.83 mm (SD:0.67 mm) and 1.07 mm (SD:0.86 mm), respectively). In the MTR group, implant placement in the anterior mandible was more accurate (p < 0.05). Additionally, MTR did not significantly increase the surgical time compared with RMR (P = 0.489). CONCLUSIONS: MTR seems to increase the accuracy of implant placement using dCAIS in comparison with the RMR method, without increasing the surgical time. The operated area seems to be relevant and might influence the implant deviations. CLINICAL SIGNIFICANCE: Considering the limitations of this in-vitro study, MTR seems to provide a higher accuracy in implant placement using dCAIS without increasing the surgical time. Furthermore, this method does not require radiographic markers and allows re-registration during surgery.

Correlation of microscopic tumor extension with tumor microenvironment in esophageal cancer patients.

OBJECTIVE: In the era of image-guided adaptive radiotherapy, definition of the clinical target volume (CTV) is a challenge in various solid tumors, including esophageal cancer (EC). Many tumor microenvironmental factors, e.g., tumor cell proliferation or cancer stem cells, are hypothesized to be involved in microscopic tumor extension (MTE). Therefore, this study assessed the expression of FAK, ILK, CD44, HIF-1α, and Ki67 in EC patients after neoadjuvant radiochemotherapy followed by tumor resection (NRCHT+R) and correlated these markers with the MTE. METHODS: Formalin-fixed paraffin-embedded tumor resection specimens of ten EC patients were analyzed using multiplex immunofluorescence staining. Since gold fiducial markers had been endoscopically implanted at the proximal and distal tumor borders prior to NRCHT+R, correlation of the markers with the MTE was feasible. RESULTS: In tumor resection specimens of EC patients, the overall percentages of FAK+, CD44+, HIF-1α+, and Ki67+ cells were higher in tumor nests than in the tumor stroma, with the outcome for Ki67+ cells reaching statistical significance (p < 0.001). Conversely, expression of ILK+ cells was higher in tumor stroma, albeit not statistically significantly. In three patients, MTE beyond the fiducial markers was found, reaching up to 31 mm. CONCLUSION: Our findings indicate that the overall expression of FAK, HIF-1α, Ki67, and CD44 was higher in tumor nests, whereas that of ILK was higher in tumor stroma. Differences in the TME between patients with residual tumor cells in the original CTV compared to those without were not found. Thus, there is insufficient evidence that the TME influences the required CTV margin on an individual patient basis. TRIAL REGISTRATION NUMBER AND DATE: BO-EK-148042017 and BO-EK-177042022 on 20.06.2022, DRKS00011886, https://drks.de/search/de/trial/DRKS00011886 .

Real-time gated proton therapy with a reduced source to imager distance: Commissioning and quality assurance.

INTRODUCTION: Real-time gated proton therapy (RGPT) is a motion management technique unique to the Hitachi particle therapy system. It uses pulsed fluoroscopy to track an implanted fiducial marker. There are currently no published guidelines on how to conduct the commissioning and quality assurance. In this work we reported on our centre's commissioning workflow and our daily and monthly QA procedures. METHODS: Six commissioning measurements were designed for RGPT. The measurements include imaging qualities, fluoroscopic exposures, RGPT marker tracking accuracy, temporal gating latency, fiducial marker tracking fidelity and an end-to-end proton dosimetry measurement. Daily QA consists of one measurement on marker localization accuracy. Four months daily QA trends are presented. Monthly QA consists of three measurementson the gating latency, fluoroscopy imaging quality and dosimetry verification of gating operation with RGPT. RESULTS: The RGPT was successfully commissioned in our centre. The air kerma rates were within 15 % from specifications and the marker tracking accuracies were within 0.245 mm. The gating latencies for turning the proton beam on and off were 119.5 and 50.0 ms respectively. The 0.4x10.0 mm2 Gold AnchorTM gave the best tracking results with visibility up to 30 g/cm2. Gamma analysis showed that dose distribution of a moving and static detectors had a passing rate of more than 95 % at 3 %/3mm. The daily marker localization QA results were all less than 0.2 mm. CONCLUSION: This work could serve as a good reference for other upcoming Hitachi particle therapy centres who are interested to use RGPT as their motion management solution.

Computerized surgical navigation resection of pelvic region simulated bone tumors using skin fiducial marker registration: an in vitro cadaveric study.

INTRODUCTION: Computerized surgical navigation system guidance can improve bone tumor surgical resection accuracy. This study compared the 10-mm planned resection margin agreement between simulated pelvic-region bone tumors (SPBT) resected using either skin fiducial markers or Kirschner (K)-wires inserted directly into osseous landmarks with navigational system registration under direct observation. We hypothesized that skin fiducial markers would display similar resection margin accuracy. METHODS: Six cadaveric pelvises had one SPBT implanted into each supra-acetabular region. At the left hemi-pelvis, the skin fiducial marker group had guidance from markers placed over the pubic tubercle, the anterior superior iliac spine, the central and more posterior iliac crest, and the greater trochanter (5 markers). At the right hemi-pelvis, the K-wire group had guidance from 1.4-mm-diameter wires inserted into the pubic tubercle, and 3 inserted along the iliac crest (4 K-wires). The senior author, a fellowship-trained surgeon performed "en bloc" SPBT resections. The primary investigator, blinded to group assignment, measured actual resection margins. RESULTS: Twenty of 22 resection margins (91%) in the skin fiducial marker group were within the Bland-Altman plot 95% confidence interval for actual-planned margin mean difference (mean = -0.23 mm; 95% confidence intervals = 2.8 mm, - 3.3 mm). Twenty-one of 22 resection margins (95%) in the K-wire group were within the 95% confidence interval of actual-planned margin mean difference (mean = 0.26 mm; 95% confidence intervals = 1.7 mm, - 1.1 mm). CONCLUSION: Pelvic bone tumor resection with navigational guidance from skin fiducial markers placed over osseous landmarks provided similar accuracy to K-wires inserted into osseous landmarks. Further in vitro studies with different SPBT dimensions/locations and clinical studies will better delineate use efficacy.

Inter-fractional error and intra-fractional motion of prostate and dosimetry comparisons of patient position registrations with versus without fiducial markers during treatment with carbon-ion radiotherapy.

A few reports have discussed the influence of inter-fractional position error and intra-fractional motion on dose distribution, particularly regarding a spread-out Bragg peak. We investigated inter-fractional and intra-fractional prostate position error by monitoring fiducial marker positions. In 2020, data from 15 patients with prostate cancer who received carbon-ion beam radiotherapy (CIRT) with gold markers were investigated. We checked marker positions before and during irradiation to calculate the inter-fractional positioning and intra-fractional movement and evaluated the CIRT dose distribution by adjusting the planning beam isocenter and clinical target volume (CTV) position. We compared the CTV dose coverages (CTV receiving 95% [V95%] or 98% [V98%] of the prescribed dose) between skeletal and fiducial matching irradiation on the treatment planning system. For inter-fractional error, the mean distance between the marker position in the planning images and that in a patient starting irradiation with skeletal matching was 1.49 ± 1.11 mm (95th percentile = 1.85 mm). The 95th percentile (maximum) values of the intra-fractional movement were 0.79 mm (2.31 mm), 1.17 mm (2.48 mm), 1.88 mm (4.01 mm), 1.23 mm (3.00 mm), and 2.09 mm (8.46 mm) along the lateral, inferior, superior, dorsal, and ventral axes, respectively. The mean V95% and V98% were 98.2% and 96.2% for the skeletal matching plan and 99.5% and 96.8% for the fiducial matching plan, respectively. Fiducial matching irradiation improved the CTV dose coverage compared with skeletal matching irradiation for CIRT for prostate cancer.