The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injury / 고신대학교의과대학학술지

Background@#Radiotherapy improves overall survival in patients with abdominopelvic malignancies. However, the toxic effects of radiation restrict the maximum dose that can be given, and there are no well-established preventive or therapeutic strategies. This study was conducted to evaluate whether rebamipide, sucralfate, and rifaximin have a suppressive effect on acute ionizing radiation (IR)-induced inflammation in the intestines of mice. @*Methods@#Thirty-six ICR mice were divided into a vehicle-treated group with sham irradiation; a vehicle-treated group with irradiation; rebamipide, sucralfate, or rifaximin-treated groups with irradiation; and a rebamipide-treated group with sham irradiation. The expression of proinflammatory, anti-inflammatory, proapoptotic, and antiapoptotic factors was investigated. @*Results@#The downregulated expression of nicotinamide phosphoribosyltransferase by IR was attenuated by all drugs (p<0.05). All drugs suppressed the IR-induced activation of NF-κB and phosphorylation of MAPKs (p<0.05) and attenuated the production of TNF-α, IL-1β, and IL-6 in response to IR (p<0.05). The administration of all drugs markedly attenuated IR-induced increases in iNOS, COX-2, and PGE2 (p<0.05), as well as [Ca2+] oscillations that were increased by IR. The expression of proapoptotic genes and antiapoptotic genes was suppressed and induced, respectively, by all drugs. IR treatment increased the release of cytochrome C, which was attenuated by all drugs (p<0.05). All drug treatments resulted in a significant decrease in the expression of caspase-3 and caspase-7 (p<0.05), which were both upregulated following IR treatment. @*Conclusions@#The administration of rebamipide, sucralfate, or rifaximin prior to radiation therapy may prevent or attenuate acute radiation-induced enterocolitis.

Gross tumor volume dependency on phase sorting methods of four-dimensional computed tomography images for lung cancer

PURPOSE: To see the gross tumor volume (GTV) dependency according to the phase selection and reconstruction methods, we measured and analyzed the changes of tumor volume and motion at each phase in 20 cases with lung cancer patients who underwent image-guided radiotherapy. MATERIALS AND METHODS: We retrospectively analyzed four-dimensional computed tomography (4D-CT) images in 20 cases of 19 patients who underwent image-guided radiotherapy. The 4D-CT images were reconstructed by the maximum intensity projection (MIP) and the minimum intensity projection (Min-IP) method after sorting phase as 40%–60%, 30%–70%, and 0%–90%. We analyzed the relationship between the range of motion and the change of GTV according to the reconstruction method. RESULTS: The motion ranges of GTVs are statistically significant only for the tumor motion in craniocaudal direction. The discrepancies of GTV volume and motion between MIP and Min-IP increased rapidly as the wider ranges of duty cycles are selected. CONCLUSION: As narrow as possible duty cycle such as 40%–60% and MIP reconstruction was suitable for lung cancer if the respiration was stable. Selecting the reconstruction methods and duty cycle is important for small size and for large motion range tumors.

Gross tumor volume dependency on phase sorting methods of four-dimensional computed tomography images for lung cancer

PURPOSE: To see the gross tumor volume (GTV) dependency according to the phase selection and reconstruction methods, we measured and analyzed the changes of tumor volume and motion at each phase in 20 cases with lung cancer patients who underwent image-guided radiotherapy. MATERIALS AND METHODS: We retrospectively analyzed four-dimensional computed tomography (4D-CT) images in 20 cases of 19 patients who underwent image-guided radiotherapy. The 4D-CT images were reconstructed by the maximum intensity projection (MIP) and the minimum intensity projection (Min-IP) method after sorting phase as 40%–60%, 30%–70%, and 0%–90%. We analyzed the relationship between the range of motion and the change of GTV according to the reconstruction method. RESULTS: The motion ranges of GTVs are statistically significant only for the tumor motion in craniocaudal direction. The discrepancies of GTV volume and motion between MIP and Min-IP increased rapidly as the wider ranges of duty cycles are selected. CONCLUSION: As narrow as possible duty cycle such as 40%–60% and MIP reconstruction was suitable for lung cancer if the respiration was stable. Selecting the reconstruction methods and duty cycle is important for small size and for large motion range tumors.

Comparison between audio-only and audiovisual biofeedback for regulating patients' respiration during four-dimensional radiotherapy

PURPOSE: To compare audio-only biofeedback to conventional audiovisual biofeedback for regulating patients' respiration during four-dimensional radiotherapy, limiting damage to healthy surrounding tissues caused by organ movement. MATERIALS AND METHODS: Six healthy volunteers were assisted by audiovisual or audio-only biofeedback systems to regulate their respirations. Volunteers breathed through a mask developed for this study by following computer-generated guiding curves displayed on a screen, combined with instructional sounds. They then performed breathing following instructional sounds only. The guiding signals and the volunteers' respiratory signals were logged at 20 samples per second. RESULTS: The standard deviations between the guiding and respiratory curves for the audiovisual and audio-only biofeedback systems were 21.55% and 23.19%, respectively; the average correlation coefficients were 0.9778 and 0.9756, respectively. The regularities between audiovisual and audio-only biofeedback for six volunteers' respirations were same statistically from the paired t-test. CONCLUSION: The difference between the audiovisual and audio-only biofeedback methods was not significant. Audio-only biofeedback has many advantages, as patients do not require a mask and can quickly adapt to this method in the clinic.

Analysis of Overall Setup Accuracy Using On-Board Imager(R) / 의학물리

We evaluated the overall setup accuracy for the On-Board Imager (OBI, Varian Medical Systems Inc., Palo Alto, CA, USA), with attention to the laser, the gantry, and operator performance. We let experienced technicians place the marker block on the couch using a lock bar system, with alignment to the isocenter of the laser, every morning. A pair of radiographic images of the marker block was acquired at 0degrees and 270degrees angles to the kV arm to correct the position using a 2D/2D matching technique. Once the desired match was achieved, the couch was moved remotely to correct the setup error and the parameters were saved. The average for the vertical and the longitudinal displacements were 0.65 mm and 0.66 mm, and 0.01 mm for the lateral displacement. The average for the vertical and longitudinal displacements were statistically significant at the 0.05 level (p value=0.000 for both), while the p value for the lateral direction was 0.829. These results show that the tendencies to displacement in vertical and longitudinal directions occur through systematic error, while systematic error was not found in the lateral displacement. This daily overall evaluation is practical and easy to find the systematic and random errors in the setup system; however, a daily QA for laser and OBI alignment is still needed to minimize the systematic error in aligning patients.

Skin Damage Sustained During Head-and-Neck and Shoulder Radiotherapy Due to the Curvature of Skin and the Use of Immobilization Mask / 의학물리

The purpose of this study was to measure curvature contour skin dose using radiochromic film and TLD for a conventional open field. We also attempted to quantify the degradation of skin sparing associated with use of immobilization devices for high energy photon beams and to calculate the skin dose with a help of Monte Carlo (MC) simulation. To simulate head-and-neck and shoulder treatment, a cylindrical solid water phantom 11 cm in diameter was irradiated with 6 MV x-rays using 40x40 cm2 field at 100 cm source axis distance (SAD) to the center of the phantom. Aquaplastic mesh mask was placed on the surface of the cylindrical phantom that mimicked relevant clinical situations. The skin dose profile was obtained by taking measurements from 0degrees to 360degrees around the circumference of the cylindrical phantom. The skin doses obtained from radiochromic film were found to be 47% of the maximum dose of D(max) at the 0degrees beam entry position and 61% at the 90degrees oblique beam position without the mask. Using the mask (1.5 mm), the skin dose received was 59% at 0degrees incidence and 78% at 80degrees incidence. Skin dose results were also gathered using thin thermoluminescent dosimeters (TLD). With the mask, the skin dose was 66% at 0degrees incidence and 80% at 80degrees incidence. This method with the mask revealed the similar pattern as film measurement. For the treatments of the head-and-neck and shoulder regions in which immobilization mask was used, skin doses at around tangential angle were nearly the same as the prescription dose. When a sloping skin contour is encountered, skin doses may be abated using thinner and more perforated immoblization devices which should still maintain immoblization.

A Method to Calculate a Pass Rate of the gamma-index Analysis in Tomotherapy Delivery Quality Assurance (DQA) / 의학물리

DQA, a patient specific quality assurance in tomotherapy, is usually performed using an ion chamber and a film. The result of DQA is analysed with the treatment planning system called Tomo Planning Station (TomoPS). The two-dimensional dose distribution of film measurement is compared with the dose distribution calculated by TomoPS using the gamma-index analysis. In gamma-index analysis, the criteria such as 3%/3 mm is used and we verify that whether the rate of number of points which pass the criteria (pass rate) is within tolerance. TomoPS does not provide any quantitative information regarding the pass rate. In this work, a method to get the pass rate of the gamma-index analysis was suggested and a software PassRT which calculates the pass rate was developed. The results of patient specific QA of the intensity modulated radiation therapy measured with I'mRT MatriXX (IBA Dosimetry, Germany) and DQA of tomotherapy measured with film were used to verify the proposed method. The pass rate was calculated using PassRT and compared with the pass rate calculated by OmniPro I'mRT (IBA Dosimetry, Germany). The average difference between the two pass rates was 0.00% for the MatriXX measurement. The standard deviation and the maximum difference were 0.02% and 0.02%, respectively. For the film measurement, average difference, standard deviation and maximum difference were 0.00%, 0.02% and 0.02%, respectively. For regions of interest smaller than 24.3x16.6 cm2 the proposed method can be used to calculate the pass rate of the gamma index analysis to one decimal place and will be helpful for the more accurate DQA in tomotherapy.

Development of Electronic Medical Chart for Radiation Oncology / 의학물리

As the radiotherapy technique development, the needs for using of medical electronic chart in the department of radiation oncology is growing. However, the complexity of affairs of radiation oncology make it difficult to develop a electronic medical chart. In this study, we introduce the electronic medical chart developed by domestic hospital. The function and example of electronic medical chart designed as radiation treatment progress was showed and the future study was presented.

Development of Electronic Medical Chart for Radiation Oncology / 의학물리

As the radiotherapy technique development, the needs for using of medical electronic chart in the department of radiation oncology is growing. However, the complexity of affairs of radiation oncology make it difficult to develop a electronic medical chart. In this study, we introduce the electronic medical chart developed by domestic hospital. The function and example of electronic medical chart designed as radiation treatment progress was showed and the future study was presented.

Verification of X-sight Lung Tracking System in the CyberKnife / 의학물리

To track moving tumor in real time, CyberKnife system imports a technique of the synchrony respiratory tracking system. The fiducial marker which are detectable in X-ray images were demand in CyberKnife Robotic radiosurgery system. It issued as reference markers to locate and track tumor location during patient alignment and treatment delivery. Fiducial marker implantation is an invasive surgical operation that carries a relatively high risk of pneumothorax. Most recently, it was developed a direct lung tumor registration method that does not require the use of fiducials. The purpose of this study is to measure the accuracy of target applying X-sight lung tracking using the Gafchromic film in dynamic moving thorax phantom. The X-sight Lung Tracking quality assurance motion phantom simulates simple respiratory motion of a lung tumor and provides Gafchromic dosimetry film-based test capability at locations inside the phantom corresponding to a typical lung tumor. The total average error for the X-sight Lung Tracking System with a moving target was 0.85+/-0.22 mm. The results were considered reliable and applicable for lung tumor treatment in CyberKnife radiosurgery system. Clinically, breathing patterns of patients may vary during radiation therapy. Therefore, additional studies with a set real patient data are necessary to evaluate the target accuracy for the X-sight Lung Tracking system.

Verification of X-sight Lung Tracking System in the CyberKnife / 의학물리

To track moving tumor in real time, CyberKnife system imports a technique of the synchrony respiratory tracking system. The fiducial marker which are detectable in X-ray images were demand in CyberKnife Robotic radiosurgery system. It issued as reference markers to locate and track tumor location during patient alignment and treatment delivery. Fiducial marker implantation is an invasive surgical operation that carries a relatively high risk of pneumothorax. Most recently, it was developed a direct lung tumor registration method that does not require the use of fiducials. The purpose of this study is to measure the accuracy of target applying X-sight lung tracking using the Gafchromic film in dynamic moving thorax phantom. The X-sight Lung Tracking quality assurance motion phantom simulates simple respiratory motion of a lung tumor and provides Gafchromic dosimetry film-based test capability at locations inside the phantom corresponding to a typical lung tumor. The total average error for the X-sight Lung Tracking System with a moving target was 0.85+/-0.22 mm. The results were considered reliable and applicable for lung tumor treatment in CyberKnife radiosurgery system. Clinically, breathing patterns of patients may vary during radiation therapy. Therefore, additional studies with a set real patient data are necessary to evaluate the target accuracy for the X-sight Lung Tracking system.

Evaluation of Difference between Skin Motion and Tumor Motion for Respiration Gated Radiotherapy / 의학물리

Accounting for tumor motion in treatment planning and delivery is one of the most recent and significant challenges facing radiotherapy. The purpose of this study was to investigate the correlation and clarified the relationship between the motion of an external marker using the Real?Time Position Management (RPM) System and an internal organ motion signal obtained fluoroscope. We enrolled 10 patients with locally advanced lung cancer and liver cancer, retrospectively. The external marker was a plastic box, which is part of the RPM used to track the patient's respiration. We investigated the quantitatively correlation between the motions of an external marker with RPM and internal motion with fluoroscope. The internal fiducial motion is predominant in the caraniocaudal direction, with a range of 1.3~3.5 cm with fluoroscopic unit. The external fiducial motion is predominant in the caraniocaudal direction, with a range of 0.43~2.19 cm with RPM gating. The two measurements ratio is from 1.31 to 5.56. When the regularization guided standard deviation is from 0.08 to 0.87, mean 0.204 cm, except only for patients #3 separated by a mean 0.13 cm, maximum of 0.23 cm. This result is a good correlation between internal tumor motion imaged by fluoroscopic unit and external marker motion with RPM during expiration within 0.23 cm. We have demonstrated that gating may be best performed but special attention should be paid to gating for patients whose fiducials do not move in synchrony, because targeting on the correct phase difference alone would not guarantee that the entire tumor volume is within the treatment field.

Clinical Implementation of an Eye Fixing and Monitoring System with Head Mount Display / 의학물리

A system to non-invasively fix and monitor eye by a head mounted display (HMD) with a CCD camera for stereotactic radiotherapy (SRS) of uveal melanoma has been developed and implemented clinically. The eye fixing and monitoring system consists of a HMD showing patient a screen for fixing eyeball, a CCD camera monitoring patient' s eyeball, and an immobilization mask. At first, patient' s head was immobilized with a mask. Then, patient was instructed to wear HMD, to which CCD camera was attached, on the mask and see the given reference point on its screen. While patient stared at the given point in order to fix eyeball, the camera monitored its motion. Four volunteers and one patient of uveal melanoma for SRS came into this study. For the volunteers, setup errors and the motion of eyeball were analyzed. For the patient, CT scans were performed, with patient' s wearing HMD and fixing the eye to the given point. To treat patient under the same condition, daily CT scans were also performed before every treatment and the motion of lens was compared to the planning CT. Setup errors for four volunteers were within 1 mm and the motion of eyeball was fixed within the clinically acceptable ranges. For the patient with uveal melanoma, the motion of lens was fixed within 2 mm from daily CT scans. An eye fixing and monitoring system allowed immobilizing patient as well as monitoring eyeball and was successfully implemented in the treatment of uveal melanoma for SRS.

Real-time Body Surface Motion Tracking using the Couch Based Computer-controlled Motion Phantom (CBMP) and Ultrasonic Sensor: A Feasibility Study / 의학물리

Respiration gating radiotherapy technique developed in consideration of the movement of body surface and internal organs during respiration, is categorized into the method of analyzing the respiratory volume for data processing and that of keeping track of fiducial landmark or dermatologic markers based on radiography. However, since these methods require high-priced equipments for treatment and are used for the specific radiotherapy. Therefore, we should develop new essential method whilst ruling out the possible problems. This study aims to obtain body surface motion by using the couch based computer-controlled motion phantom (CBMP) and US sensor, and to develop respiration gating techniques that can adjust patients' beds by using opposite values of the data obtained. The CBMP made to measure body surface motion is composed of a BS II microprocessor, sensor, host computer and stepping motor etc. And the program to control and operate it was developed. After the CBMP was adjusted by entering random movement data, and the phantom movements were acquired using the sensors, the two data were compared and analyzed. And then, after the movements by respiration were acquired by using a rabbit, the real-time respiration gating techniques were drawn by operating the phantom with the opposite values of the data. The result of analyzing the acquisition-correction delay time for the data value shows that the data value coincided within 1% and that the acquisition-correction delay time was obtained real-time (2.34 x 10(-4) sec). And the movement was the maximum movement was 6 mm in Z direction, in which the respiratory cycle was 2.9 seconds. This study successfully confirms the clinical application possibility of respiration gating techniques by using a CBMP and sensor.

The Effect of the CT Number for Each CT on Dose Calculation / 의학물리

The CT number corresponds to electron density and its influence on dose calculation was studied. Five kinds of CT scanners were used to obtain images of electron density calibration phantom (Gammex RMI 467). Then the differences between CT numbers for each scanners were +/-2% in homogeneous medium and 9.5% in high density medium. In order to investigate the influence of CT number to dose calculation, patients' thoracic CT images were analyzed. The maximum dose difference was 0.48% for each organ. It acquired the phantom images inserted high density material in the water phantom. Comparing the doses calculated with CT images from each CT scanner, the maximum dose difference was 2.1% in 20 cm in depth. The exact density to CT number conversion according to CT scanner is required to minimize the uncertainty of dose depends on CT number. Especially the each hospital with various CT scanners has to discriminate CT numbers for each CT scanner. Moreover a periodic quality assurance is required for reproducibility of CT number.

Study of Respiration Simulating Phantom using Thermocouple-based Respiration Monitoring Mask / 대한방사선종양학회지

PURPOSE: To develop the respiration simulating phantom with thermocouple for evaluating 4D radiotherapy such as gated radiotherapy, breathing control radiotherapy and dynamic tumor tracking radiotherapy. MATERIALS AND METHODS: The respiration monitoring mask (ReMM) with thermocouple was developed to monitor the patient's irregular respiration. The signal from ReMM controls the simulating phantom as organ motion of patients in real-time. The organ and the phantom motion were compared with its respiratory curves to evaluate the simulating phantom. ReMM was used to measure patients' respiration, and the movement of simulating phantom was measured by using RPM(R). The fluoroscope was used to monitor the patient's diaphragm motion. RESULTS: Comparing with the curves of respiration measured by thermocouple and those of the organ motion measured by fluoroscope and RPM, the standard deviations between the curves were 9.68% and 8.53% relative to the organ motion, respectively. The standard deviation of discrepancy between the respiratory curve and the organ motion was 8.52% of motion range. CONCLUSION: Patients felt comfortable with ReMM. The relationship between the signal from ReMM and the organ motion shows strong correlation. The phantom simulates the organ motion in real-time according to the respiratory signal from the ReMM. It is expected that the simulating phantom with ReMM could be used to verify the 4D radiotherapy.