UNASSIGNED: Precise patient positioning with image guidance (IGRT) is essential for safe prostate radiotherapy. We present the first report of utilizing a CT-visible hydrogel spacer, used to decrease rectal radiation dose, as a surrogate fiducial marker to aid in daily IGRT with cone-beam CT (CBCT) in stereotactic radiotherapy (SABR) for prostate cancer.
UNASSIGNED: Prior to CT simulation, patients underwent placement of three intraprostatic gold fiducial markers and radiopaque hydrogel spacer per standard practice. At treatment, after initial setup, a CBCT was acquired and fused to the planning CT based on 3-dimensional matching of the spacer. A second alignment was then performed based on the fiducial markers. The six directional shifts (three linear and three rotational) were recorded, and the differences compared.
UNASSIGNED: 140 individual fractions across 41 consecutive patients were evaluated. Mean/median differences between hydrogel spacer-based and fiducial-based alignment in linear (vertical, longitudinal, lateral) and rotational (rotation, pitch, roll) shifts were 0.9/0.6mm, 0.8/0.5mm, and 0.6/0.4mm, and 0.38/0, 0.62/0, and 0.35/0 degrees, respectively. No difference was observed in 9.9%, 22.9%, and 22.14% of linear shifts, and 65.7%, 65%, and 66.4% rotational shifts, respectively. Significantly smaller differences were observed in the latter 70 fractions vs. the former, and results were consistent across evaluators.
UNASSIGNED: For precise daily IGRT with CBCT for prostate SABR, alignment using a radiopaque hydrogel spacer was highly comparable to intraprostatic fiducial markers. This represents the first report supporting an additional indication of IGRT for a CT-visible hydrogel spacer, to further enhance treatment accuracy and potentially obviate the need for the additional fiducial marker procedure.

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.

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.

OBJECTIVE: To provide more accurate and definitive conclusions regarding the clinical and technical complications associated with the transperineal (TP) and transrectal (TR) approaches, a comprehensive review of observational studies and randomized controlled trials was conducted. This systematic review covered all eligible studies to facilitate a thorough comparison of complications linked to the two fiducial marker insertion methods, TP and TR.
METHODS: A comprehensive search of the literature was conducted, encompassing databases such as PubMed, Embase, and the Cochrane Library, up to July 7, 2023. The relative risk and 95% confidence interval were utilized to evaluate the diagnosis and complication rates.
RESULTS: The final selection for the methodological quality analysis included 13 observational studies that utilized TP and TR gold fiducial insertion approaches. The meta-analysis revealed significantly lower risks of urinary tract infections (UTI) and rectal bleeding with the TP approach.
CONCLUSIONS: The use of both TP and TR techniques for placing gold seed fiducial markers has proven to be an effective, safe, and well-tolerated method for image-guided radiation therapy in prostate cancer patients. A significant benefit of the TP technique is its ability to avoid rectal puncture, thereby reducing the risk of UTIs. Although the incidence of UTIs and rectal bleeding associated with the TR method is relatively low, these complications can disrupt patient wellbeing and potentially cause delays in treatment.

BACKGROUND: 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.
CONCLUSIONS: 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.

BACKGROUND: Preclinical models of radiotherapy (RT) response are vital for the continued success and evolution of RT in the treatment of cancer. The irradiation of tissues in mouse models necessitates high levels of precision and accuracy to recapitulate clinical exposures and limit adverse effects on animal welfare. This requirement has been met by technological advances in preclinical RT platforms established over the past decade. Small animal RT systems use onboard computed tomography (CT) imaging to delineate target volumes and have significantly refined radiobiology experiments with major 3Rs impacts. However, the CT imaging is limited by the differential attenuation of tissues resulting in poor contrast in soft tissues. Clinically, radio-opaque fiducial markers (FMs) are used to establish anatomical reference points during treatment planning to ensure accuracy beam targeting, this approach is yet to translate back preclinical models.
METHODS: We report on the use of a novel liquid FM BioXmark ® developed by Nanovi A/S (Kongens Lyngby, Denmark) that can be used to improve the visualisation of soft tissue targets during beam targeting and minimise dose to surrounding organs at risk. We present descriptive protocols and methods for the use of BioXmark ® in experimental male and female C57BL/6J mouse models.
RESULTS: These guidelines outline the optimum needle size for uptake (18-gauge) and injection (25- or 26-gauge) of BioXmark ® for use in mouse models along with recommended injection volumes (10-20 µl) for visualisation on preclinical cone beam CT (CBCT) scans. Injection techniques include subcutaneous, intraperitoneal, intra-tumoral and prostate injections.
CONCLUSIONS: The use of BioXmark ® can help to standardise targeting methods, improve alignment in preclinical image-guided RT and significantly improve the welfare of experimental animals with the reduction of normal tissue exposure to RT.

BACKGROUND: Dynamic navigation for implant placement is becoming popular under the concept of top-down treatment. The purpose of this study is to verify the accuracy of a dynamic navigation system for implant placement.
METHODS: Implant placement was performed on 38 patients using 50 implant fixtures. Patients in group C were treated using a conventional method, in which thermoplastic clips were fixed to the teeth, and patients in group M were treated using thermoplastic clips fixed to a mouthpiece attached to the teeth. The groups were compared to verify whether an accuracy difference existed. A treatment planning support program for dental implants was used to superimpose the postoperative computed tomography data on the preoperative implant design data to measure the entry point, apex point, and angular deviation.
RESULTS: The accuracy of group C was 1.36 ± 0.51 mm for entry point, 1.30 ± 0.59 mm for apex point, and 3.20 ± 0.74° for angular deviation. The accuracy of group M was 1.06 ± 0.31 mm for the entry point, 1.02 ± 0.30 mm for the apex point, and 2.91 ± 0.97° for angular deviation. Significant differences were observed in the entry and apex points between the two groups.
CONCLUSIONS: The results indicate that group M exhibited better accuracy than group C, indicating that the stability of the thermoplastic clip is important for ensuring the accuracy of the dynamic navigation system. No previous studies have verified the accuracy of this system using the mouthpiece method, and additional data is required to confirm its accuracy for dental implant placement. The mouthpiece method improves the accuracy of implant placement and provides a safer implant treatment than the conventional method.
BACKGROUND: University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), Registration Number: UMIN000051949, URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view_his.cgi on August 21, 2023.

An experimental validation of a robotic system for radioactive iodine-125 seed implantation (RISI) in tumor treatment was conducted using customized phantom models and animal models simulating liver and lung lesions. The robotic system, consisting of planning, navigation, and implantation modules, was employed to implant dummy radioactive seeds into the models. Fiducial markers were used for target localization. In phantom experiments across 40 cases, the mean errors between planned and actual seed positions were 0.98 ± 1.05 mm, 1.14 ± 0.62 mm, and 0.90 ± 1.05 mm in the x, y, and z directions, respectively. The x, y, and z directions correspond to the left-right, anterior-posterior, and superior-inferior anatomical planes. Silicone phantoms exhibiting significantly smaller x-axis errors compared to liver and lung phantoms (p < 0.05). Template assistance significantly reduced errors in all axes (p < 0.05). No significant dosimetric deviations were observed in parameters such as D90, V100, and V150 between plans and post-implant doses (p > 0.05). In animal experiments across 23 liver and lung cases, the mean implantation errors were 1.28 ± 0.77 mm, 1.66 ± 0.69 mm, and 1.86 ± 0.93 mm in the x, y, and z directions, slightly higher than in phantoms (p < 0.05), with no significant differences between liver and lung models. The dosimetric results closely matched planned values, confirming the accuracy of the robotic system for RISI, offering new possibilities in clinical tumor treatment.

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.
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.
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).
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.
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.

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.
CONCLUSIONS: 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.
UNASSIGNED: BO-EK-148042017 and BO-EK-177042022 on 20.06.2022, DRKS00011886, https://drks.de/search/de/trial/DRKS00011886 .