Search

Boron Neutron Capture Therapy (BNCT) has recently been used in clinical oncology thanks to recent developments of accelerator-based BNCT systems. Although there are some specific processes for BNCT, they have not yet been discussed in detail.The aim of this study is to provide comprehensive data on the risk of accelerator-based BNCT system to institutions planning to implement an accelerator-based BNCT system.In this study, failure mode and effects analysis (FMEA) was performed based on a treatment process map prepared for the accelerator-based BNCT system. A multidisciplinary team consisting of a medical doctor (MD), a registered nurse (RN), two medical physicists (MP), and three radiologic technologists (RT) identified the failure modes (FMs). Occurrence (O), severity (S), and detectability (D) were scored on a scale of 10, respectively. For each failure mode (FM), risk priority number (RPN) was calculated by multiplying the values of O, S, and D, and it was then categorized as high risk, very high risk, and other. Additionally, FMs were statistically compared in terms of countermeasures, associated occupations, and whether or not they were the patient-derived.The identified FMs for BNCT were 165 in which 30 and 17 FMs were classified as high risk and very high risk, respectively. Additionally, 71 FMs were accelerator-based BNCT-specific FMs in which 18 and 5 FMs were classified as high risk and very high risk, respectively. The FMs for which countermeasures were "Education" or "Confirmation" were statistically significantly higher for S than the others (p = 0.019). As the number of BNCT facilities is expected to increase, staff education is even more important. Comparing patient-derived and other FMs, O tended to be higher in patient-derived FMs. This could be because the non-patient-derived FMs included events that could be controlled by software, whereas the patient-derived FMs were impossible to prevent and might also depend on the patient's condition. Alternatively, there were non-patient-derived FMs with higher D, which were difficult to detect mechanically and were classified as more than high risk. In O, significantly higher values (p = 0.096) were found for FMs from MD and RN associated with much patient intervention compared to FMs from MP and RT less patient intervention. Comparing conventional radiotherapy and accelerator-based BNCT, although there were events with comparable risk in same FMs, there were also events with different risk in same FMs. They could be related to differences in the physical characteristics of the two modalities.This study is the first report for conducting a risk analysis for BNCT using FMEA. Thus, this study provides comprehensive data needed for quality assurance/quality control (QA/QC) in the treatment process for facilities considering the implementation of accelerator-based BNCT in the future. Because many BNCT-specific risks were discussed, it is important to understand the characteristics of BNCT and to take adequate measures in advance. If the effects of all FMs and countermeasures are discussed by multidisciplinary team, it will be possible to take countermeasures against individual FMs from many perspectives and provide BNCT more safely and effectively.

This study aimed to clarify the differences in radiotherapy dose characteristics and delivery efficiency between the supine and prone positions in patients with prostate cancer using the CyberKnife. The planning computed tomography (CT) and delineations of the prone position were obtained by rotating the supine CT images with delineations of 180° using image processing software. The optimization parameters for planning target volume (PTV) and organs at risk (OARs) were based on the prone position. The optimization parameters determined for the prone position were applied to the supine position for optimization and dose calculation. The dosimetric characteristics of the PTV and OARs, and delivery efficiency were compared between the two different patient positions. The plans in the prone position resulted in better PTV conformity index (nCI), rectum V90%, V80%, V75%, V50% and bladder V50%. A significant difference was observed in treatment time and depth along the central axis (dCAX) between the two plans. The mean treatment time per fraction and dCAX for the supine and prone positions were 20.9 ± 1.7 min versus 19.8 ± 1.3 min (P = 0.019) and 151.1 ± 33.6 mm versus 233.2 ± 8.8 mm (P

Currently, tongue cancers are primarily managed by surgery, and interstitial brachytherapy is only recommended for a selected group of early state T1-2N0 patients who refuse surgery or are medically inoperable. In this report, a case with T3N2cM0 tongue cancer who has been effectively treated by the combination of concurrent chemoradiotherapy involving volumetric arc therapy and boost high-dose rate interstitial brachytherapy is presented. Of course, surgery remains the main treatment strategy for tongue cancer patients; however, the authors believe that if volumetric arc therapy is carefully planned to reduce the mandible dose as much as possible and high-dose rate interstitial brachytherapy with a mouthpiece that protects the mandible is combined, it is possible to treat T3N2 disease, and this can be considered for patients who want to preserve organ function.

To assess the accuracy of the movement of a brachytherapy source using a high-speed camera for evaluating source position, dwell time, and transit dose.A high-speed camera was used to record the source position of an Ir-192 source relative to a ruler within a custom positioning jig in a remote afterloading system. The analyzed frames can be used to assess dwell positions and times. Treatment plans had multiple dwell times equal to 0.1, 0.5, 1.0, and 2.0 s in 2.5- and 5-mm step sizes. Images were acquired at a rate of 146 frames/s. Acquired images were processed to automatically track the actual source using the correlation between a template image and each frame. The brachytherapy dose calculation formalism (AAPM TG43-U1) was applied to each frame to evaluate the transit dose contribution to the total dose.The differences in measured source positions from the nominal for dwell times equal to 0.1, 0.5, 1.0, and 2.0 s in treatment plans were approximately ≤1 mm. The corresponding differences in measured dwell times from the nominal values at 5 mm steps were -15, -9, -5, and 5 ms, respectively. The source velocities at 5 mm steps were approximately 393 mm/s. The dose differences at 5 mm from the source movement with and without the transit dose for these dwell times were 38%, 7%, 3%, and 2%, respectively.Recording a brachytherapy source using a high-speed camera allowed the evaluation of positional and dwell time accuracies as well as dosimetry assessments, such as the transit dose, based on the application of AAPM TG-43U1.

PURPOSE In this study, we report on our proposed phantom based on the new end-to-end (E2E) methodology and its results. In addition, we verify whether the proposed phantom can replace conventional phantoms. METHODS The hexagonal-shaped newly designed phantom has pockets on each side for a film dosimeter of size 80 × 90 mm2 , which is easily removable, considering the 60 Co penumbra. The new phantom comprises water, shell, and auxiliary shell phantoms. The shell and auxiliary shell materials are Solid Water HE. A mock tumor (aluminum oxide) was attached by a single prop in the water phantom and placed at the center of the new phantom. The results of a conventional E2E test were compared with those of the novel E2E test using the newly designed phantom. The irradiated film dosimeter in the novel E2E test was scanned in a flatbed scanner and analyzed using an in-house software developed with MATLAB. The irradiated field center, laser center, and mock tumor center were calculated. In the novel image-matching E2E (IM-E2E) test, image matching is performed by aligning the laser center with ruled lines. In the novel irradiation-field E2E (IF-E2E) test, the displacement of the irradiation-field center was defined as its distance from the laser center. In the composite E2E test, the overall displacement, which included the accuracy of the irradiated field and image matching, was defined as the distance between the irradiated field center and mock tumor center. In addition, using the newly designed phantom, the overall irradiation accuracy of the machine was evaluated by calculating the three-dimensional (3D) center of the irradiated field, phantom, and laser. The composite E2E test could be performed using the newly designed phantom only. RESULTS In the IM-E2E test, the results of the conventional and novel IM-E2E tests were significantly different in each direction (left-right direction: p-value

Background Contour delineation, a crucial process in radiation oncology, is time-consuming and inaccurate due to inter-observer variation has been a critical issue in this process. An atlas-based automatic segmentation was developed to improve the delineation efficiency and reduce inter-observer variation. Additionally, automated segmentation using artificial intelligence (AI) has recently become available. In this study, auto-segmentations by atlas- and AI-based models for Organs at Risk (OAR) in patients with prostate and head and neck cancer were performed and delineation accuracies were evaluated. Methods Twenty-one patients with prostate cancer and 30 patients with head and neck cancer were evaluated. MIM Maestro was used to apply the atlas-based segmentation. MIM Contour ProtégéAI was used to apply the AI-based segmentation. Three similarity indices, the Dice similarity coefficient (DSC), Hausdorff distance (HD), and mean distance to agreement (MDA), were evaluated and compared with manual delineations. In addition, radiation oncologists visually evaluated the delineation accuracies. Results Among patients with prostate cancer, the AI-based model demonstrated higher accuracy than the atlas-based on DSC, HD, and MDA for the bladder and rectum. Upon visual evaluation, some errors were observed in the atlas-based delineations when the boundary between the small bowel or the seminal vesicle and the bladder was unclear. For patients with head and neck cancer, no significant differences were observed between the two models for almost all OARs, except small delineations such as the optic chiasm and optic nerve. The DSC tended to be lower when the HD and the MDA were smaller in small volume delineations. Conclusions In terms of efficiency, the processing time for head and neck cancers was much shorter than manual delineation. While quantitative evaluation with AI-based segmentation was significantly more accurate than atlas-based for prostate cancer, there was no significant difference for head and neck cancer. According to the results of visual evaluation, less necessity of manual correction in AI-based segmentation indicates that the segmentation efficiency of AI-based model is higher than that of atlas-based model. The effectiveness of the AI-based model can be expected to improve the segmentation efficiency and to significantly shorten the delineation time.

The setup of lung shield (LS) in total body irradiation (TBI) with the computed radiography (CR) system is a time-consuming task and has not been quantitatively evaluated. The TBI mobile imager (TBI-MI) can solve this problem through real-time monitoring. Therefore, this study aimed to perform commissioning and performance evaluation of TBI-MI to promote its use in clinical practice.The source-axis distance in TBI treatment, TBI-MI (CNERGY TBI, Cablon Medical B.V.), and the LS position were set to 400, 450, and 358 cm, respectively. The evaluation items were as follows: accuracy of image scaling and measured displacement error of LS, image quality (linearity, signal-to-noise ratio, and modulation transfer function) using an EPID QC phantom, optimal thresholding to detect intra-fractional motion in the alert function, and the scatter radiation dose from TBI-MI.The accuracy of image scaling and the difference in measured displacement of the LS was 4 mm in any displacements and directions. The image quality of TBI imager was slightly inferior to the CR image but was visually acceptable in clinical practice. The signal-to-noise ratio was improved at high dose rate. The optimal thresholding value to detect a 10-mm body displacement was determined to be approximately 5.0%. The maximum fraction of scattering radiation to irradiated dose was 1.7% at patient surface.MI-TBI can quantitatively evaluate LS displacement with acceptable image quality. Furthermore, real-time monitoring with alert function to detect intrafraction patient displacement can contribute to safe TBI treatment.

Purpose This study compared the applicator position relative to the tracheal wall and dosimetric parameters between conventional and novel applicators among patients receiving endobronchial brachytherapy (EBBT) for intratracheal tumors. Methods and Materials Data from 7 patients who received EBBT for intratracheal tumors were retrospectively analyzed; 4 and 3 patients were treated with conventional (2-wing) or novel (5-wing) applicators, respectively. Applicator centrality was evaluated using the distance between the center of the trachea and main bronchus (TMB) lumen and path of source (L). Dosimetric parameters, including plans normalized to D2cc of the TMB = 45 Gy (normalized plan), were compared between the applicators. Results The mean and maximum values of L in cases of the 2-wing applicator group were approximately 5.0 mm and 10.0 mm, respectively. In the novel applicator group, the corresponding values were approximately 3.0 and 6.0 mm, respectively. In the normalized plan of the 2-wing applicator group, the ranges of median V90% of clinical target volume (CTV) and D0.1cc of the TMB in all cases were 23.0–91.9% and 66.3–153.1 Gy, respectively. In the 5-wing applicator group, the corresponding values were 69.2–83.8% and 60.4–84.5 Gy, respectively. Conclusions In the 5-wing applicator group, the range was narrow in all dose–volume parameters except for D2cc of the TMB. Compared to the conventional applicator, the 5-wing applicator can give a stable dose to the CTV and can reduce the maximum dose of the TMB. This suggests that stable EBBT can be given to any patient using the 5-wing applicator.

Purpose In this single-institution retrospective study, configuration analysis was performed to determine the optimal location and volume of hyaluronic acid gel spacer injection into the rectovaginal or vesicovaginal septum for effective dose reduction (DR) to the organs at risk (OARs), the rectum and bladder. Methods and materials 70 and 50 intracavitary brachytherapy treatment plans used only vaginal cylinders with gel spacers for the rectal and bladder sides, respectively, whereas 28 did not use spacers. Correlation analysis was performed between the geometrical parameters and injection position of the gel spacers and the 2-cm3 covering doses of the OARs for each treatment. Results A higher DR was predicted for hyaluronic acid gel spacer injection within ±5 mm and ±2.5 mm in the lateral-medial direction from the midpoint on the rectal and bladder sides, and ±10 mm in the cranial–caudal direction from the midpoint on the rectal side. There were correlations between 2-cm3 covering doses and the gel spacer parameters: the volume on the rectal (p = 0.02) and bladder (p = 0.04) sides; the craniocaudal length on the rectal side (p > 0.05). Conclusions A gel spacer volume of ∼10 cm3 provides sufficient OAR DR if its gravity point is on the midpoint between the cylinder applicator and OAR, and its craniocaudal length covers the active length of the cylinder applicator.

Purpose This study aimed to develop a deep convolutional neural network (CNN)-based dose distribution conversion approach for the correction of the influence of a magnetic field for online MR-guided adaptive radiotherapy. Methods Our model is based on DenseNet and consists of two 2D input channels and one 2D output channel. These three types of data comprise dose distributions without a magnetic field (uncorrected), electron density (ED) maps, and dose distributions with a magnetic field. These data were generated as follows: both types of dose distributions were created using 15-field IMRT in the same conditions except for the presence or absence of a magnetic field with the GPU Monte Carlo dose in Monaco version 5.4; ED maps were acquired with planning CT images using a clinical CT-to-ED table at our institution. Data for 50 prostate cancer patients were used; 30 patients were allocated for training, 10 for validation, and 10 for testing using 4-fold cross-validation based on rectum gas volume. The accuracy of the model was evaluated by comparing 2D gamma-indexes against the dose distributions in each irradiation field with a magnetic field (true). Results The gamma indexes in the body for CNN-corrected uncorrected dose against the true dose were 94.95% ± 4.69% and 63.19% ± 3.63%, respectively. The gamma indexes with 2%/2-mm criteria were improved by 10% in most test cases (99.36%). Conclusions Our results suggest that the CNN-based approach can be used to correct the dose-distribution influences with a magnetic field in prostate cancer treatment.

The first magnetic resonance (MR)-guided radiotherapy system in Japan was installed in May 2017. Implementation of online MR-guided adaptive radiotherapy (MRgART) began in February 2018. Online MRgART offers greater treatment accuracy owing to the high soft-tissue contrast in MR-images (MRI), compared to that in X-ray imaging. The Japanese Society for Magnetic Resonance in Medicine (JSMRM), Japan Society of Medical Physics (JSMP), Japan Radiological Society (JRS), Japanese Society of Radiological Technology (JSRT), and Japanese Society for Radiation Oncology (JASTRO) jointly established the comprehensive practical guidelines for online MRgART. These guidelines propose the essential requirements for clinical implementation of online MRgART with respect to equipment, personnel, institutional environment, practice guidance, and quality assurance/quality control (QA/QC). The minimum requirements for related equipment and QA/QC tools, recommendations for safe operation of MRI system, and the implementation system are described. The accuracy of monitor chamber and detector in dose measurements should be confirmed because of the presence of magnetic field. The ionization chamber should be MR-compatible. Non-MR-compatible devices should be used in an area that is not affected by the static magnetic field (outside the five Gauss line), and their operation should be checked to ensure that they do not affect the MR image quality. Dose verification should be performed using an independent dose verification system that has been confirmed to be reliable through commissioning. This guideline proposes the checklists to ensure the safety of online MRgART. Successful clinical implementation of online MRgART requires close collaboration between physician, radiological technologist, nurse, and medical physicist.

Background: Soy isoflavones and their metabolites such as equol have been associated with a reduced risk of hormone-sensitive tumors and metabolic syndromes. However, individual soy isoflavones and equol levels in atopic dermatitis remain uninvestigated. Objective: The aim of this study is to compare the levels of urinary daidzein, genistein, and equol between atopic dermatitis patients and normal subjects and to examine the correlation between equol concentration and the severity of clinical symptoms. Methods: A cross-sectional study was conducted at Akita University Hospital and Aso Iizuka Hospital in Japan. Fifty patients with confirmed atopic dermatitis diagnosis and 67 healthy controls were recruited. Daidzein, genistein, and equol in urine were measured by using a high-performance liquid chromatography-mass spectrometry system. Results: Urinary equol levels were significantly lower in the atopic dermatitis patients than in the healthy controls (p = 0.002). The difference was particularly noticeable in young people (6–19 years, p < 0.001). No correlations were found between urinary equol levels and the severity of clinical symptoms and laboratory data in the atopic dermatitis patients. Conclusion: Equol levels in childhood might be involved in the development of atopic dermatitis.

Background and PurposeHigh-dose-rate interstitial brachytherapy (HDR-ISBT) is recommended to obtain a better local tumor control for uterine cancer patients in specific situations such as bulky lesions, an extension to the lateral parametrium, or tumors with irregular shapes. Our group uses real-time transrectal ultrasonography (TRUS) to guide freehand interstitial needle insertion. Occasionally, target tumors locate deeper beyond the rectum and cannot be visualized by TRUS. CT can guide needles to deeply located tumors, but in such cases, repeated image obtainment is required to achieve ideal needle localization. In this report, we present nine cases of patients who underwent HDR-ISBT for deeply situated tumors guided by a combination of transrectal and transabdominal ultrasonography (TR/TA-US).Material and MethodsNine uterine cancer patients whose tumors were located deeper than the reach of TRUS and underwent HDR-ISBT guided by TR/TA-US were presented. All nine cases had no distal organ metastasis and underwent external beam radiation therapy (EBRT) to the pelvic region for 45–50.4 Gy in 25–28 fractions followed by boost HDR-ISBT for deeply situated tumors guided by TR/TA-US.ResultsThere were seven cervical cancer and two endometrial cancer patients: six with extensive uterine corpus invasion, one cervical cancer with massive pelvic lymph node metastasis, one cervical cancer with postoperative pelvic recurrence, and one with left ovarian direct tumor invasion. The median follow-up period was 15 months (range 3–28 months). The average clinical target volume at the time of first HDR-ISBT was 131 ml (range 44–335 ml). The linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy of nine cases was 14.0 (9.0–17.0) cm. HDR-ISBT dose fractionation was 24–30 Gy in four or five fractions. Seven out of nine cases had no local recurrence in the follow-up period. One had local in-field recurrence 25 months after HDR-ISBT. Another case with carcinosarcoma could not obtain local control and underwent salvage hysterectomy for a residual uterine tumor 11 months after HDR-ISBT. Four cases had extra-field recurrence in lymph nodes or distant organs.ConclusionsIn brachytherapy for gynecologic malignancies, deeply situated tumors located out of reach of TRUS may obtain favorable local control by HDR-ISBT guided with TR/TA-US.

Purpose To increase the superficial dose and reduce the brain dose for radiotherapy of scalp angiosarcoma, we propose a novel irradiation technique of tangential irradiation volumetric modulated arc therapy (TI-VMAT). Methods TI-VMAT and the conventional VMAT treatment plans for thirteen scalp angiosarcoma patients were created with a prescribed dose of 70 Gy. Each treatment was normalized to cover 95% of the planning target volume (PTV) with its prescribed dose. To realize TI-VMAT, an avoidance structure (AS) function was applied. AS was defined as a contour subtracted PTV by a certain space from the brain contour. TI-VMAT treatment plans for six different spaces between PTV and AS were developed and compared with the conventional VMAT treatment plan with respect to the following dosimetric parameters: homogeneity index (HI) and conformity index (CI) of the PTV, mean brain dose, and brain volume irradiated with 20% (V20% [cc]), 40% (V40% [cc]), 60% (V60% [cc]), 80% (V80% [cc]), and 100% (V100% [cc]) of the prescribed dose. Results HI and CI were comparable between TI-VMAT and the conventional VMAT, the mean brain dose for TI-VMAT with AS defined by a space of 2.0 cm and jaw tracking was 14.27 Gy, which was significantly lower than that for the conventional VMAT (21.20 Gy). In addition, dosimetric parameters such as V20% [cc] were significantly suppressed compared to those for high doses. Conclusion Our proposed irradiation technique TI-VMAT shows the potential to reduce radiation doses in the brain with maintaining higher dose coverage on the PTV.

Mycosis fungoides (MF) is a common, low-grade non-Hodgkin’s lymphoma of skin-homing T lymphocytes that can be treated via skin-directed radiotherapy. Our institution has implemented total skin electron therapy (TSET) with a 4.3 m source-to-surface distance (SSD) and 6 MeV electron beams with a beam spoiler. A 35-year-old male undergoing TSET desired to avoid radiotherapy-induced hair loss and temporary infertility; therefore, leakage dose to scalp and testicles was reduced with a special radiation shield composed of stacked lead sheets. The shields for the scalp and scrotal were of 3 mm and 6 mm, respectively. To assess leakage doses, a radiophotoluminescence glass dosimeter (RPLD) was placed at every fraction. The difference dose between the measured and prescribed dose at the calibration point was 2%. The top of the head and scrotal surface exhibited 18 cGy and 10 cGy, respectively. Thus, the dose to the scrotal surface was not beyond the testicular tolerance dose of 20 cGy. Results of semen analysis two months postradiotherapy were normal. There was no hair loss during or after radiation therapy. Therefore, the RPLD is a useful in vivo dosimeter that provides technical information on radiation shielding to allow for completion of TSET without hair loss or temporary infertility.

The purpose of the study was to compare a 3D convolutional neural network (CNN) with the conventional machine learning method for predicting intensity-modulated radiation therapy (IMRT) dose distribution using only contours in prostate cancer. In this study, which included 95 IMRT-treated prostate cancer patients with available dose distributions and contours for planning target volume (PTVs) and organs at risk (OARs), a supervised-learning approach was used for training, where the dose for a voxel set in the dataset was defined as the label. The adaptive moment estimation algorithm was employed for optimizing a 3D U-net similar network. Eighty cases were used for the training and validation set in 5-fold cross-validation, and the remaining 15 cases were used as the test set. The predicted dose distributions were compared with the clinical dose distributions, and the model performance was evaluated by comparison with RapidPlan™. Dose–volume histogram (DVH) parameters were calculated for each contour as evaluation indexes. The mean absolute errors (MAE) with one standard deviation (1SD) between the clinical and CNN-predicted doses were 1.10% ± 0.64%, 2.50% ± 1.17%, 2.04% ± 1.40%, and 2.08% ± 1.99% for D2, D98 in PTV-1 and V65 in rectum and V65 in bladder, respectively, whereas the MAEs with 1SD between the clinical and the RapidPlan™-generated doses were 1.01% ± 0.66%, 2.15% ± 1.25%, 5.34% ± 2.13% and 3.04% ± 1.79%, respectively. Our CNN model could predict dose distributions that were superior or comparable with that generated by RapidPlan™, suggesting the potential of CNN in dose distribution prediction.

An accelerator-based boron neutron capture therapy (BNCT) system employing a solid-state Li target can achieve sufficient neutron flux for treatment although the neutron flux is reduced over the lifetime of its target. In this study, the reduction was examined in the five targets, and a model was then established to represent the neutron flux. In each target, a reduction in neutron flux was observed based on the integrated proton charge on the target, and its reduction reached 28% after the integrated proton charge of 2.52 × 106 mC was delivered to the target in the system. The calculated neutron flux acquired by the model was compared to the measured neutron flux based on an integrated proton charge, and the mean discrepancies were less than 0.1% in all the targets investigated. These discrepancies were comparable among the five targets examined. Thus, the reduction of the neutron flux can be represented by the model. Additionally, by adequately revising the model, it may be applicable to other BNCT systems employing a Li target, thus furthering research in this direction. Therefore, the established model will play an important role in the accelerator-based BNCT system with a solid-state Li target in controlling neutron delivery and understanding the neutron output characteristics.

Endothelin-1 (ET-1) is well known as the most potent vasoconstrictor, and can evoke histamine-independent pruritus. Recently, its involvement in cutaneous inflammation has begun to draw attention. The upregulation of ET-1 expression in the epidermis of human psoriasis patients has been reported. It was also demonstrated that ET-1 can stimulate dendritic cells to induce Th17/1 immune responses. However, the role of the interaction between ET-1 and ET-1 receptors in the pathogenesis of psoriasis remains elusive. Here, we investigated the effects of ET-1 receptor antagonist on imiquimod (IMQ) -induced psoriasiform dermatitis in mouse. Psoriasis-related cytokines such as IL-17A and TNF-α induced ET-1 expression in human keratinocytes. Topical application of selective endothelin A receptor (ETAR) antagonist ambrisentan significantly attenuated the development of IMQ-induced psoriasiform dermatitis and also significantly inhibited the histological inflammation and cytokine expression (TNF-α, IL-12p40, IL-12 p19, and IL-17) in the lesional skin of the mouse model. Furthermore, topical application of ambrisentan suppressed phenotypic and functional activation of dendritic cells in lymph nodes. Our findings indicate that the ET-1 and ETAR axis plays an important role in the pathogenesis of psoriasis and is a potential therapeutic target for treating psoriasis.

The quality of radiotherapy has greatly improved due to the high precision achieved by intensity-modulated radiation therapy (IMRT). Studies have been conducted to increase the quality of planning and reduce the costs associated with planning through automated planning method; however, few studies have used the deep learning method for optimization of planning. The purpose of this study was to propose an automated method based on a convolutional neural network (CNN) for predicting the dosimetric eligibility of patients with prostate cancer undergoing IMRT. Sixty patients with prostate cancer who underwent IMRT were included in the study. Treatment strategy involved division of the patients into two groups, namely, meeting all dose constraints and not meeting all dose constraints, by experienced medical physicists. We used AlexNet (i.e., one of common CNN architectures) for CNN-based methods to predict the two groups. An AlexNet CNN pre-trained on ImageNet was fine-tuned. Two dataset formats were used as input data: planning computed tomography (CT) images and structure labels. Five-fold cross-validation was used, and performance metrics included sensitivity, specificity, and prediction accuracy. Class activation mapping was used to visualize the internal representation learned by the CNN. Prediction accuracies of the model with the planning CT image dataset and that with the structure label dataset were 56.7 ± 9.7% and 70.0 ± 11.3%, respectively. Moreover, the model with structure labels focused on areas associated with dose constraints. These results revealed the potential applicability of deep learning to the treatment planning of patients with prostate cancer undergoing IMRT.

Purpose An accurate source model of a medical linear accelerator is essential for Monte Carlo (MC) dose calculations. This study aims to propose an analytical photon source model based on particle transport in parameterized accelerator structures, focusing on a more realistic determination of linac photon spectra compared to existing approaches. Methods We designed the primary and secondary photon sources based on the photons attenuated and scattered by a parameterized flattening filter. The primary photons were derived by attenuating bremsstrahlung photons based on the path length in the filter. Conversely, the secondary photons were derived from the decrement of the primary photons in the attenuation process. This design facilitates these sources to share the free parameters of the filter shape and be related to each other through the photon interaction in the filter. We introduced two other parameters of the primary photon source to describe the particle fluence in penumbral regions. All the parameters are optimized based on calculated dose curves in water using the pencil-beam-based algorithm. To verify the modeling accuracy, we compared the proposed model with the phase space data (PSD) of the Varian TrueBeam 6 and 15 MV accelerators in terms of the beam characteristics and the dose distributions. The EGS5 Monte Carlo code was used to calculate the dose distributions associated with the optimized model and reference PSD in a homogeneous water phantom and a heterogeneous lung phantom. We calculated the percentage of points passing 1D and 2D gamma analysis with 1%/1 mm criteria for the dose curves and lateral dose distributions, respectively. Results The optimized model accurately reproduced the spectral curves of the reference PSD both on- and off-axis. The depth dose and lateral dose profiles of the optimized model also showed good agreement with those of the reference PSD. The passing rates of the 1D gamma analysis with 1%/1 mm criteria between the model and PSD were 100% for 4 × 4, 10 × 10, and 20 × 20 cm2 fields at multiple depths. For the 2D dose distributions calculated in the heterogeneous lung phantom, the 2D gamma pass rate was 100% for 6 and 15 MV beams. The model optimization time was less than 4 min. Conclusion The proposed source model optimization process accurately produces photon fluence spectra from a linac using valid physical properties, without detailed knowledge of the geometry of the linac head, and with minimal optimization time.

OVOLs (OVO-like proteins) are ubiquitously conserved genes encoding a C2H2 zinc finger transcription factor in mammals. Functional studies on OVOL1 and OVOL2 using knockout mice have suggested that these genes play a pivotal role in the development of epithelial tissues arising from germ cells; however, the role of the OVOL1–OVOL2 axis in normal and diseased tissues remains unclear. This review highlights recent advances in understanding how the OVOL1–OVOL2 axis modulates cell differentiation and proliferation in human keratinocytes, hair follicles, and benign or malignant skin tumors including squamous cell carcinoma and malignant melanoma. Furthermore, OVOL1 has been shown to be involved in the expression of skin barrier proteins including filaggrin (FLG), and its mutation or dysfunction leads to the development of atopic dermatitis (AD). OVOL1 has also been identified as a susceptibility gene for AD by genome-wide association studies, in addition to FLG. Therefore, we discuss the relationship between OVOL1 and FLG in the development of AD.

We clarified the reconstructed 3D dose difference between two different commercial software programs (Mobius3D v2.0 and PerFRACTION v1.6.4). Five prostate cancer patients treated with IMRT (74 Gy/37 Fr) were studied. Log files and cine EPID images were acquired for each fraction. 3D patient dose was reconstructed using log files (Mobius3D) or log files with EPID imaging (PerFRACTION). The treatment planning dose was re-calculated on homogeneous and heterogeneous phantoms, and log files and cine EPID images were acquired. Measured doses were compared with the reconstructed point doses in the phantom. Next, we compared dosimetric metrics (mean dose for PTV, rectum, and bladder) calculated by Mobius3D and PerFRACTION for all fractions from five patients. Dose difference at isocenter between measurement and reconstructed dose for two software programs was within 3.0% in both homogeneous and heterogeneous phantoms. Moreover, the dose difference was larger using skip arc plan than that using full arc plan, especially for PerFRACTION (e.g., dose difference at isocenter for PerFRACTION: 0.34% for full arc plan vs. -4.50% for skip arc plan in patient 1). For patients, differences in dosimetric parameters were within 1% for almost all fractions. PerFRACTION had wider range of dose difference between first fraction and the other fractions than Mobius3D (e.g., maximum difference: 0.50% for Mobius3D vs. 1.85% for PerFRACTION), possibly because EPID may detect some types of MLC positioning errors such as miscalibration errors or mechanical backlash which cannot be detected by log files, or that EPID data might include image acquisition failure and image noise.

Objective Mamushi (Gloydius blomhoffii) snakebite is the most common type of snake injury in Japan and is also seen in China and Korea. Although the components of Mamushi venom have been investigated, epidemiological and clinical descriptions still remain limited in the English literature. The aim of this study was to review the clinical features and management of patients with injuries related to Mamushi snakebites. Methods We conducted a retrospective examination of 114 Mamushi snakebite cases encountered at a general hospital in Japan from January 2004 to November 2016. Data were collected from the medical records. Results We found that Mamushi snakebites commonly occurred during summer and the daytime, with elderly men typically being affected. The symptom grade at initial consultation was significantly worse in the walk-in group than in the ambulance admission group, probably due to treatment delay. The number of fangs that pierced the skin was not related to the severity of the symptoms. The group treated with a tourniquet more frequently exhibited exacerbation of symptoms than those that received other treatments (p

Atopic dermatitis (AD) is a chronic inflammatory condition with complex etiology, including genetic, environmental and immunologic factors. Redox imbalance caused by excessive oxidative stress has been shown to mediate disease activity of AD. Currently, an imaging technique that can monitor the redox status of the skin in vivo has not yet been developed. Consequently, we have established such a technique that can detect and visualize the redox status of the skin using in vivo dynamic nuclear polarization magnetic resonance imaging (DNP-MRI). To evaluate this technique, we utilized an AD mouse model that was generated by repeated topical application of mite antigen in NC/Nga mice. We imaged alterations in redox balance of the resulting AD skin lesions of the mice. Using in vivo DNP-MRI and non-toxic nitroxyl radicals to visualize free radicals in vivo, we revealed that AD skin lesions demonstrated more rapid decay rates of image intensity enhancement than normal skin, indicating that our technique can monitor excessive oxidative stress occurring in AD skin lesions. Therefore, this technique has the potential to provide a novel approach for evaluating disease activity of inflammatory skin diseases, including AD, from the view point of altered redox status.

Background Members of the interleukin (IL)-36 family, IL-36α, IL-36β and IL-36γ, are potent chemoattractive cytokines for neutrophils and eosinophils. IL-36 receptor antagonist (IL-36Ra) inhibits IL-36α, IL-36β and IL-36γ activity. However, the immunohistological expression of IL-36α, IL-36β, IL-36γ and IL-36Ra has never been addressed in normal follicles, folliculitis or eosinophilic pustular folliculitis (EPF). Methods We performed immunohistochemical staining for IL-36α, IL-36β, IL-36γ and IL-36Ra using 10 cases of EPF, nine of non-specific folliculitis, 10 normal skin samples and 10 samples of normal follicles adjacent to a sebaceous naevus as a control. Two dermatologists, who were blind to the patient records, evaluated all of the slides. Results The immunoreactive IL-36α was hardly detected in the follicular epithelium and epidermis in the normal skin, folliculitis or EPF. The expression of IL-36β, IL-36γ and IL-36Ra was augmented in both folliculitis and EPF compared with that in normal follicles. Negative correlations were detected between IL-36β and IL-36Ra and between IL-36γ and IL-36Ra in normal follicles; however, these were absent in folliculitis. In contrast to normal follicles and folliculitis, a significant positive correlation between IL-36β/γ and IL-36Ra was shown in EPF. Conclusions The overexpression of IL-36β, IL-36γ and IL-36Ra is an integral part of the inflammatory response of folliculitis and EPF. The coordinated expression of IL-36γ and IL-36Ra may be related to the pathomechanism of EPF.

The purpose of this study was to evaluate and compare the dosimetric effects of HyperArc-based stereotactic radiosurgery (SRS) and a robotic radiosurgery system-based planning using CyberKnife for multiple cranial metastases. In total, 11 cancer patients with multiple cranial metastases (3 to 5 tumors) treated with CyberKnife were examined. These patients were replanned using HyperArc (Varian Medical Systems, Palo Alto, USA). HyperArc plan were designed using 4 noncoplanar arc single-isocenter VMAT in 6 MV flattening filter free mode for simulated delivery with the True beam STx (Varian). The prescription dose was 23 Gy at single fraction. Dosimetric differences and blinded clinician scoring differences were evaluated. Conformity index (CI) and gradient index (GI) were 0.60 ± 0.11 and 3.94 ± 0.74, respectively, for the CyberKnife plan and 0.87 ± 0.08 and 5.31 ± 1.42, respectively, for the HyperArc plan (p < 0.05). Total brain V12-gross tumor volumes (GTVs) for the CyberKnife and HyperArc plans were 5.26 ± 2.83 and 4.02 ± 1.71 cm3, respectively. These results indicate that HyperArc plan showed better CI and total brain V12-GTV, while CyberKnife plan showed better GI. A blinded physician scoring evaluation did not show significant differences between CyberKnife and HyperArc plans. The HyperArc-based SRS plan is comparable with the CyberKnife plan, suggesting a greater potential to emerge as a suitable tool for SRS of multiple brain metastases.