Lateral response artifact correction method using image stitching technique in radiochromic film dosimetry.

PURPOSE: Lateral response artifact (LRA) is caused by the interaction between film and flatbed scanner in the direction perpendicular to the scanning direction. This can significantly affect the accuracy of patient-specific quality assurance (QA) in cases involving large irradiation fields. We hypothesized that by utilizing the central area of the flatbed scanner, where the magnitude of LRA is relatively small, the LRA could be mitigated effectively. This study proposes a practical solution using the image-stitching technique to correct LRA for patient-specific QA involving large irradiation fields. METHODS: Gafchromic™ EBT4 film and Epson Expression ES-G11000 flatbed scanner were used in this study. The image-stitching algorithm requires a spot between adjacent images to combine them. The film was scanned at three locations on a flatbed scanner, and these images were combined using the image-stitching technique. The combined film dose was then calculated and compared with the treatment planning system (TPS)-calculated dose using gamma analysis (3%/2 mm). Our proposed LRA correction was applied to several films exposed to 18 × 18 cm2 open fields at doses of 200, 400, and 600 cGy, as well as to four clinical Volumetric Modulated Arc Therapy (VMAT) treatment plans involving large fields. RESULTS: For doses of 200, 400, and 600 cGy, the gamma analysis values with and without LRA corrections were 95.7% versus 67.8%, 95.5% versus 66.2%, and 91.8% versus 35.9%, respectively. For the clinical VMAT treatment plan, the average pass rate ± standard deviation in gamma analysis was 94.1% ± 0.4% with LRA corrections and 72.5% ± 1.5% without LRA corrections. CONCLUSIONS: The effectiveness of our proposed LRA correction using the image-stitching technique was demonstrated to significantly improve the accuracy of patient-specific QA for VMAT treatment plans involving large irradiation fields.

Kaposi's sarcoma-associated herpesvirus replication and transcription activator protein activates CD274/PD-L1 gene promoter.

Kaposi's sarcoma-associated herpesvirus (KSHV) is responsible for the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. The expression of immunosuppressive genes, such as IL-10 and CD274/PD-L1 is observed during KSHV-associated pathogenesis, and the modulation of the host immune system by KSHV contributes to establishing viral persistence in the host. Understanding the mechanism that allows the virus to evade host cell immunity would be helpful in order to develop therapeutic strategies for KSHV malignancy. In this study, we show that KSHV replication and transcriptional activator (K-RTA), an essential activator of the viral lytic cycle, transactivates the CD274/PD-L1 gene promoter. Mechanistically, we demonstrate that the binding of K-RTA to the cellular specificity protein 1 (SP1) is critical for K-RTA-mediated CD274/PD-L1 promoter activation. These findings suggest that K-RTA cooperates with intracellular SP1 to activate the expression of CD274/PD-L1, which helps the virus regulate immune checkpoints to escape and survive.

[Improvement of Nonuniformity on Flatbed Scanner for Radiochromic Film Dosimetry Using Average Correction Factor with Multi-direction Scan Data].

In order to correct the lateral effect caused by the light source of the flatbed scanner in the Gafchromic film EBT3, the usefulness of the correction method using the average value of the correction coefficient considering the scan directions were evaluated. EBT3 was scanned from four directions to measure the optical density (OD) of the red, blue, and, red/blue components and the correction coefficient were calculated. For the correction coefficients, average values were calculated for the purpose of use, when the scan directions could not be aligned (average lateral effect correction). Correction accuracy was verified with the pass rate of gamma analysis (3 mm/3%, threshold 30%) of the dose distribution using the EBT3 film irradiated with the step pattern. OD of the red, blue, and, red/blue components in the scanning vertical direction tended to be higher in the center than in the peripheral portion. The pass rate of the step pattern was the red component's before correction, from 26.9 to 45.1% (before correction), from 84.1 to 96.7% (after correction), the red/blue component, from 37.6 to 48.4% (before correction) and from 84.4 to 96.7% (after correction). When using the correction coefficient using the average value, the pass rate was 89.8% for the red component and 94.7% for the red/blue component. The lateral effect correction improves the accuracy of the dose distribution verification, and the correction coefficient using the average value is useful when the scanning direction is different from that at the time of obtaining the dose concentration curve.

IL-10 promoter transactivation by the viral K-RTA protein involves the host-cell transcription factors, specificity proteins 1 and 3.

Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 (HHV-8) causes a persistent infection, presenting latent and lytic replication phases during its life cycle. KSHV-related diseases are associated with deregulated expression of inflammatory cytokines, including IL-6 and IL-10, but the mechanisms underlying this dysregulation are unclear. Herein, we report a molecular mechanism for KSHV-induced IL-10 gene expression. KSHV replication and transcription activator (K-RTA) is a molecular switch for the initiation of expression of viral lytic genes, and we describe, for the first time, that K-RTA significantly activates the promoter of the human IL-10 gene. Of note, mutations involving a basic region of K-RTA reduced the association of K-RTA with the IL-10 promoter. Moreover, the host-cell transcription factors, specificity proteins (SP) 1 and 3, play a pivotal cooperative role in K-RTA-mediated transactivation of the IL-10 promoter. K-RTA can interact with SP1 and SP3 directly in vitro, and electrophoresis mobility shift assays (EMSAs) revealed co-operative interaction involving K-RTA, SP1, and SP3 in binding to the IL-10 promoter. As DNase I footprinting assays indicated that K-RTA did not affect SP3 binding to the IL-10 promoter, SP3 can function to recruit K-RTA to the IL-10 promoter. These findings indicate that K-RTA can directly contribute to IL-10 up-regulation via a functional interplay with the cellular transcription factors SP1 and SP3.

[Evaluation of 3D Dose Distribution and Clinical Applications Using Polymer Gel Dosimeter].

Evaluation of dosimetric impact of the interplay effect between multi-leaf collimator (MLC) movement and tumor respiratory motion during volumetric modulated arc therapy (VMAT) delivery using polymer gel dosimeter was taken as an example in this article. An excellent gas barrier PAN (polyacrylonitrile) bottle filled with polyacrylamide-based gel dosimeter contained magnesium chloride as a sensitizer (iPAGAT dosimeter) was set to the QUASAR™ respiratory motion phantom (Modus), and was moved with motion amplitudes (peak-to-peak amplitude) of 1 and 2 cm with a 4 second period during VMAT delivery by the Novalis Tx linear accelerator (Varian/BrainLAB). Two spherical GTVs with 2 cm diameter and two PTVs were defined considering the respiratory motion and setup uncertainties. Three-dimensional (3D) dose distribution in iPAGAT dosimeter was read out by the 3T MRI system, and was evaluated by the dose profiles, gamma analysis and the dose-volume histogram (DVH) using in-house developed software. As a result, interplay effect was negligible since dose coverage of GTV was sufficient during VMAT delivery with simulated respiratory motion.

Reconsideration of the Iwasaki-Waggener iterative perturbation method for reconstructing high-energy X-ray spectra.

We have reviewed applicable ranges for attenuating media and off-axis distances regarding the high-energy X-ray spectra reconstructed via the Iwasaki-Waggener iterative perturbation method for 4-20 MV X-ray beams. Sets of in-air relative transmission data used for reconstruction of spectra were calculated for low- and high-Z attenuators (acrylic and lead, respectively) by use of a functional spectral formula. More accurate sets of spectra could be reconstructed by dividing the off-axis distances of R = 0-20 cm into two series of R = 0-10 cm and R = 10-20 cm, and by taking into account the radiation attenuation and scatter in the buildup cap of the dosimeter. We also incorporated in the reconstructed spectra an adjustment factor (f (adjust) ≈ 1) that is determined by the attenuating medium, the acceleration voltage, and the set of off-axis distances. This resulted in calculated in-air relative transmission data to within ±2 % deviation for the low-Z attenuators water, acrylic, and aluminum (Al) with 0-50 cm thicknesses and R = 0-20 cm; data to within ±3 % deviation were obtained for high-Z attenuators such as iron (Fe), copper (Cu), silver (Ag), tungsten (W), platinum (Pt), gold (Au), lead (Pb), thorium (Th), and uranium (U) having thicknesses of 0-10 cm and R = 0-20 cm. By taking into account the radiation attenuation and scatter in the buildup cap, we could analyze the in-air chamber response along a line perpendicular to the isocenter axis.

[Testing of dynamic multileaf collimator by dynamic log file].

Intensity-modulated radiation therapy (IMRT) represents one of the most significant technical advances in radiation therapy. In the dynamic multileaf collimator (MLC) method of IMRT delivery, because of the relatively small gaps between opposed leaves and because most regions are shielded by leaves most of the time, the delivered dose is very sensitive to MLC leaf positional accuracy. A variation of +/-0.2 mm in the gap width can result in a dose variation of +/-3% for each clinical dynamic MLC field. Most often the effects of leaf motion are inferred from dose deviations on film or from variations in ionization measurements. These techniques provide dosimetric information but do not provide detailed information for diagnosing delivery problems. Therefore, a dynamic log file (Dynalog file) was used to verify dynamic MLC leaf positional accuracy. Measuring for narrow gaps using the thickness gauge could detect a log file accuracy of approximately 0.1 mm. The accuracy of dynamic MLC delivery depends on the accuracy with which the velocity of each leaf is controlled. We studied the relationship between leaf positional accuracy and leaf velocity. Leaf velocity of 0.7 cm/sec caused approximately 0.2 mm leaf positional variation. We then analyzed leaf positional accuracy for the clinical dynamic MLC field using Dynalog File Viewer (Varian Medical Systems, Inc., Palo Alto, CA), and developed a new program that can analyze more detailed leaf motions. Using this program, we can obtain more detailed information, and therefore can determine the source of dose uncertainties for the dynamic MLC field.

[Evaluation of the accuracy of a compensating filter based on compact NC-Mill for radiation therapy].

The present report describes the fabrication technique and dosimetry aspects of a desktop numerically controlled milling machine (NC-Mill) based a compensator system that uses lead clay (Shield cray, Reactor Experiments, Inc., U.S.A.). Effective path lengths of patients were determined for CT image sets using the ray-tracing technique and converted to compensator thickness with the equivalent TMR method. Rigid urethane foam was processed with the NC-Mill to produce a mold for filters, and the lead clay was adopted as the compensating material. The dose distribution was measured on the compensating plane of an anthropomorphic phantom and a stair-step PMMA phantom. It was found that the radiation field with inhomogeneous dose was as high as 30%+/-3% with the compensating filters. In addition, when the absorbed dose at the central axis of 52 compensating filters that were used clinically was measured, 75.0% showed an error of less than +/-3%, and 3.8% showed the maximum dose error: >+/-5%. Overall, the present system was capable of producing dose uniformity to within +/-5% for a stair-step phantom, an anthropomorphic phantom, and clinical situations.

Radiophotoluminescence dosimetry using a small spherical glass: a preliminary phantom study.

A radiophotoluminescence dosimetry has been proposed using a spherical silver-activated phosphate glass with a diameter of 1.5 mm. A 6 MV photon dose of 2 Sv (2 Gy) was delivered to 14 spherical glass samples placed between two solid water phantoms at a depth of 10 cm. The samples were positioned within a 20 x 20 mm(2) centred at beam axis to ensure uniform dose absorption. A normalised output from a read-out system was obtained by simultaneously measuring luminescence from a non-irradiated reference and that from an irradiated reference to eliminate background contamination and time-varying fluctuation of the readout system, leading to a normalised standard deviation of 1.8%. A dose up to 3.5 Sv (3.5 Gy) was delivered to three spherical glass samples positioned between two solid water phantoms at a depth of 10 cm. The normalised output increased linearly with the applied dose.

[Management of home care for the advanced cancer patient from the standpoint of home hospice].

We offer home hospice care to patients with bowel obstruction associated with advanced gastrointestinal cancer, who hope to leave hospital and be cared at home, if they understand their condition and if their families also hope to live with the patients, so that the patients can live at home to the last breath. To master various palliative techniques and nursing care services are indispensable to assure home hospice care. In this case, 1. guidance about HPN, 2. guidance about pain control, 3. arrangement of visiting nurse services and 4. application for the long-term care insurance and procurement of the bed and other nursing goods needed to be completed before the discharge from the hospital, and it is important to complete these preparations rapidly in a short period. The 24-hour communication system and appropriate care for new symptoms are the key for successfully shifting to home hospice care. At the final stage, it is important to support families and repeatedly provide guidance for the peaceful death.

[Management of home care for the advanced cancer patient from the standpoint of home hospice].

We offer home hospice care to patients with bowel obstruction associated with advanced gastrointestinal cancer, who hope to leave hospital and be cared at home, if they understand their condition and if their families also hope to live with the patients, so that the patients can live at home to the last breath. To master various palliative techniques and nursing care services are indispensable to assure home hospice care. In this case, (1) guidance about HPN, (2) guidance about pain control, (3) arrangement of visiting nurse services and (4) application for the long-term care insurance and procurement of the bed and other nursing goods needed to be completed before the discharge from the hospital, and it is important to complete these preparations rapidly in a short period. The 24 hour communication system and appropriate care for new symptoms are the key for successfully shifting to home hospice care. At the final stage, it is important to support families and repeatedly provide guidance for the peaceful death.

[Usefulness of a dose distribution analysis system with a common scanner].

Although one-dimensional densitometry has been widely performed for linac dosimetry, it is a time-consuming, labor-intensive procedure. We studied a new densitometry system (DD-System) that consists of a personal computer and common flatbed-type scanner, with regard to its usefulness for daily QC checks in comparison with conventional densitometry. The spatial resolution of the DD-System is very high, and its accuracy of measurements of field size and flatness are equivalent to those of a conventional system at an optical density <2.0. Although the performance of the image scanner limits the maximum optical density of our system, this system can acquire high-resolution two-dimensional dose distributions quickly and easily. In conclusion, the DD-System is very useful for reducing the amount of time and effort required in daily QC activities. We consider this system applicable to the analysis of complicated dose distributions in this era of IMRT.