[Development of a System for Evaluating the In-room-laser Alignment Including the Horizontality and Verticality Integrated the Light/Radiation Field Coincidence Test and the Winston-Lutz Test].

PURPOSE: The in-room laser which is used for patient positioning in radiotherapy is generally projected on the radiation isocenter determined by the Winston-Lutz test and so on. In this study, a couch-mounted verification device was developed that could evaluate all in-room lasers' alignment including the horizontality and verticality at one time. The device has the function to perform the light/radiation field coincidence test and the Winston-Lutz test at the same time. The aim of this report was to introduce the verification procedure for two tests, using the newly developed software and device, and to present the tuning flow of the in-room laser. Moreover, the analysis accuracy of the developed software was evaluated in comparison with commercial software. METHODS: First, the light/radiation field was evaluated by using tungsten markers on the central surface of the device. Next, after aligning the long-carved lines on the front and sides of the device with the in-room lasers, the Winston-Lutz test was carried out by using the tungsten sphere in the center of the device. The acquired images were collectively analyzed using the developed software equipped with the reporting function. Additionally, the result of this Winston-Lutz test was compared with the result from commercial software. RESULTS: A series of the light/radiation field coincidence test and the Winston-Lutz test were analyzed using the developed device and software. The results could be easily confirmed using the reporting function of the software. Regarding the result of the Winston-Lutz test, most of the analysis differences between the developed software and commercially available software were within the pixel size (0.22 mm). DISCUSSIONS: Since the accuracy of the radiation field affects the result of the Winston-Lutz test, the presented procedure of performing the light/radiation coincidence field test in advance facilitates the interpretation of the error of the Winston-Lutz test. Based on the results of the Winston-Lutz test, we were able to demonstrate the tuning flow of all in-room lasers including the horizontality and verticality by using the developed device. CONCLUSIONS: We have developed a couch-mounted verification device and software that can evaluate the light/radiation coincidence field test and the alignment including the horizontality and verticality of the in-room laser used for patient positioning in radiotherapy, and reported its usefulness. The analysis accuracy of the developed software was comparable to that of commercially available software. The use of this device and the developed software would contribute to not only the efficiency of adjusting all in-room lasers' alignment including the horizontality and verticality but also reflect accurately the result of the Winston-Lutz test.

A patient with medulloblastoma in its early developmental stage.

Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups- WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)-since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap-that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

Antitumor effect of fibrin glue containing temozolomide against malignant glioma.

Temozolomide (TMZ), used to treat glioblastoma and malignant glioma, induces autophagy, apoptosis and senescence in cancer cells. We investigated fibrin glue (FG) as a drug delivery system for the local administration of high-concentration TMZ aimed at preventing glioma recurrence. Our high-power liquid chromatography studies indicated that FG containing TMZ (TMZ-FG) manifested a sustained drug release potential. We prepared a subcutaneous tumor model by injecting groups of mice with three malignant glioma cell lines and examined the antitumor effect of TMZ-FG. We estimated the tumor volume and performed immunostaining and immunoblotting using antibodies to Ki-67, cleaved caspase 3, LC3 and p16. When FG sheets containing TMZ (TMZ-FGS) were inserted beneath the tumors, their growth was significantly suppressed. In mice treated with peroral TMZ plus TMZ-FGS the tumors tended to be smaller than in mice whose tumors were treated with TMZ-FGS or peroral TMZ alone. The TMZ-FGS induced autophagy, apoptosis and senescence in subcutaneous glioma tumor cells. To assess the safety of TMZ-FG for normal brain, we placed it directly on the brain of living mice and stained tissue sections obtained in the acute and chronic phase immunohistochemically. In both phases, TMZ-FG failed to severely damage normal brain tissue. TMZ-FG may represent a safe new drug delivery system with sustained drug release potential to treat malignant glioma.

New treatment strategies to eradicate cancer stem cells and niches in glioblastoma.

Glioblastoma multiforme (GBM) harbors are not only rapidly dividing cells but also small populations of slowly dividing and dormant cells with tumorigenesity, self-renewal, and multi-lineage differentiation capabilities. Known as glioblastoma stem cells (GSCs), they are resistant to conventional chemo- and radiotherapy and may be a causative factor in recurrence. The treatment outcome in patients with GBM remains unsatisfactory and their mean survival time has not improved sufficiently. We studied clinical evidence and basic research findings to assess the possibility of new treatment strategies that target GSCs and their specific microenvironments (GBM niches) and raise the possibility of adding new treatments to eradicate GSCs and GBM niches.

Computerized estimation of patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy.

We have developed a computerized method for estimating patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy. The patient setup errors were estimated based on a template-matching technique that compared the portal image and a localized pelvic template image with a clinical target volume produced from a digitally reconstructed radiography (DRR) image of each patient. We evaluated the proposed method by calculating the residual error between the patient setup error obtained by the proposed method and the gold standard setup error determined by consensus between two radiation oncologists. Eleven training cases with prostate cancer were used for development of the proposed method, and then we applied the method to 10 test cases as a validation test. As a result, the residual errors in the anterior-posterior, superior-inferior and left-right directions were smaller than 2 mm for the validation test. The mean residual error was 2.65 ± 1.21 mm in the Euclidean distance for training cases, and 3.10 ± 1.49 mm for the validation test. There was no statistically significant difference in the residual error between the test for training cases and the validation test (P = 0.438). The proposed method appears to be robust for detecting patient setup error in the treatment of prostate cancer radiotherapy.

Estimation of focal and extra-focal radiation profiles based on Gaussian modeling in medical linear accelerators.

The X-ray source or focal radiation is one of the factors that can degrade the conformal field edge in stereotactic body radiotherapy. For that reason, it is very important to estimate the total focal radiation profiles of linear accelerators, which consists of X-ray focal-spot radiation and extra-focal radiation profiles. Our purpose in this study was to propose an experimental method for estimating the focal-spot and extra-focal radiation profiles of linear accelerators based on triple Gaussian functions. We measured the total X-ray focal radiation profiles of the accelerators by moving a slit in conjunction with a photon field p-type silicon diode. The slit width was changed so that the extra-focal radiation could be optimally included in the total focal radiation. The total focal radiation profiles of an accelerator at 4-MV and 10-MV energies were approximated with a combination of triple Gaussian functions, which correspond to the focal-spot radiation, extra-focal radiation, and radiation transmitted through the slit assembly. As a result, the ratios of the Gaussian peak value of the extra-focal radiation to that of the focal spot for 4 and 10 MV were 0.077 and 0.159, respectively. The peak widths of the focal-spot and extra-focal radiation profiles were 0.57 and 25.0 mm for 4 MV, respectively, and 0.60 and 22.0 mm for 10 MV, respectively. We concluded that the proposed focal radiation profile model based on the triple Gaussian functions may be feasible for estimating the X-ray focal-spot and extra-focal radiation profiles.

Breath-hold monitoring and visual feedback for radiotherapy using a charge-coupled device camera and a head-mounted display: system development and feasibility.

PURPOSE: The aim of this study was to present the technical aspects of the breath-hold technique with respiratory monitoring and visual feedback and to evaluate the feasibility of this system in healthy volunteers. METHODS AND MATERIALS: To monitor respiration, the vertical position of the fiducial marker placed on the patient's abdomen was tracked by a machine vision system with a charge-coupled device camera. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. Five healthy male volunteers were enrolled in this study. They held their breath at the end-inspiration and the end-expiration phases. They performed five repetitions of the same type of 15-s breath-holds with and without a head-mounted display, respectively. A standard deviation of five mean positions of the fiducial marker during a 15-s breath-hold in each breath-hold type was used as the reproducibility value of breath-hold. RESULTS: All five volunteers well tolerated the breath-hold maneuver. For the inspiration breath-hold, the standard deviations with and without visual feedback were 1.74 mm and 0.84 mm, respectively (P = 0.20). For the expiration breath-hold, the standard deviations with and without visual feedback were 0.63 mm and 0.96 mm, respectively (P = 0.025). CONCLUSION: Our newly developed system might help the patient achieve improved breath-hold reproducibility.

Reproducibility of the abdominal and chest wall position by voluntary breath-hold technique using a laser-based monitoring and visual feedback system.

PURPOSE: The voluntary breath-hold (BH) technique is a simple method to control the respiration-related motion of a tumor during irradiation. However, the abdominal and chest wall position may not be accurately reproduced using the BH technique. The purpose of this study was to examine whether visual feedback can reduce the fluctuation in wall motion during BH using a new respiratory monitoring device. METHODS AND MATERIALS: We developed a laser-based BH monitoring and visual feedback system. For this study, five healthy volunteers were enrolled. The volunteers, practicing abdominal breathing, performed shallow end-expiration BH (SEBH), shallow end-inspiration BH (SIBH), and deep end-inspiration BH (DIBH) with or without visual feedback. The abdominal and chest wall positions were measured at 80-ms intervals during BHs. RESULTS: The fluctuation in the chest wall position was smaller than that of the abdominal wall position. The reproducibility of the wall position was improved by visual feedback. With a monitoring device, visual feedback reduced the mean deviation of the abdominal wall from 2.1 +/- 1.3 mm to 1.5 +/- 0.5 mm, 2.5 +/- 1.9 mm to 1.1 +/- 0.4 mm, and 6.6 +/- 2.4 mm to 2.6 +/- 1.4 mm in SEBH, SIBH, and DIBH, respectively. CONCLUSIONS: Volunteers can perform the BH maneuver in a highly reproducible fashion when informed about the position of the wall, although in the case of DIBH, the deviation in the wall position remained substantial.

Stereotactic radiotherapy for lung and liver tumors using a body cast system: setup accuracy and preliminary clinical outcome.

PURPOSE: To evaluate the feasibility and treatment outcomes of stereotactic radiotherapy (SRT) using a newly developed simple body cast system for lung and liver tumors. MATERIALS AND METHODS: From April 2003 to July 2004, 20 patients were treated with SRT at the Kyushu University Hospital. Thirteen patients had primary lung cancer, 5 had metastatic lung cancer, and 2 had hepatocellular carcinoma. All patients were fixed with a thermoplastic body cast combined with a vacuum pillow, arm and leg support, and a carbon plate. SRT was given in 5-8 fields with an isocenter dose of 48-60 Gy in 4-10 fractions. Target verification was performed by computed tomography (CT) during the first session, and by anterior-posterior (A-P) and lateral portal images during the second and subsequent sessions. RESULTS: The average setup errors and deviation in the first treatment session were 1.4 +/- 1.2, 1.1 +/- 1.0, and 3.3 +/- 2.8 mm in the lateral, A-P, and cranio-caudal (C-C) directions, respectively. The setup errors in the second and subsequent sessions were 2.4 +/- 0.5, 1.4 +/- 1.8, and 3.7 +/- 2.6 mm in the lateral, A-P, and C-C directions, respectively. The patient's movement during a treatment session was within 5 mm in any direction. Despite the short follow-up periods (1-15 months), complete response was shown in 4 lesions, and partial response was shown in 15 lesions. Neither local progression nor serious complication was observed in any patient. CONCLUSION: SRT using our body cast system was a safe and reliable treatment method for extracranial tumors.

A machine vision system with CCD cameras for patient positioning in radiotherapy: a preliminary report.

PURPOSE: To determine positioning accuracy of a machine vision system in radiotherapy. MATERIALS AND METHODS: The machine vision system was composed of 640 x 480 pixel CCD cameras and computerized control systems. For image acquisition, the phantom was set up for the reference position and a single CCD camera was positioned 1.5 m from the isocenter. The image data of the fiducial marker with 1.5 mm lead pellet on the lateral surface of the phantom was captured onto the CCD, and then the position of the marker was accurately calculated. The phantom was moved 0.25, 0.50, 0.75, 1.00, 2.00, and 3.00 mm from the reference position, using a micrometer head. The position of the fiducial marker was analyzed using a kilo-voltage fluoroscopic imaging system and a machine vision system. RESULTS: Using fluoroscopic images, the discrepancy between the actual movement of the phantom by micrometer heads and the measurement was found to be 0.12 +/- 0.05 mm (mean +/- standard deviation). In contrast, the detection of the movement by the machine vision system coincided with the discrepancy of 0.0067 +/- 0.0048 mm. CONCLUSION: This study suggests that the machine vision system can be used to measure small changes in patient position with a resolution of less than 0.1 mm.