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Supplementary Figures 1-6. Supplementary Figure 1. Mouse models of RIPF. Supplementary Figure 2. The ocurrence of EndMT and an EMT in the development of RIPF. Supplementary Figure 3. 2-ME inhibits EMT in the development of RIPF. Supplementary Figure 4. 2-ME inhibits RIPF. Supplementary Figure 5. H&E staining in human RIPF tissues Supplementary Figure 6. Whole-body or thoracic irradiation of mice induces apoptosis and detachment of lung endothelial cells.

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a late side effect of thoracic radiotherapy. The purpose of our study was to gain further insight into the development of RIPF.Experimental Design/Results: Here, we observed that irradiation of mouse lungs induced collagen deposition, particularly around blood vessels, in the early phase of RIPF. Such deposition subsequently became evident throughout the irradiated tissues. Accompanied by the collagen deposition, vascular EndMT (endothelial-to-mesenchymal transition) began to develop in the early phase of RIPF, before the appearance of EMT (epithelial-to-mesenchymal transition) of alveolar epithelial (AE) II cells in the substantive fibrotic phase. Concomitant with the EndMT, we detected vascular endothelial cell (EC)–specific hypoxic damage in the irradiated lung tissues. In human pulmonary artery endothelial cells (HPAEC), the radiation-induced EndMT via activation of TGFβ-R1/Smad signaling was dependent on HIF1α expression. A novel HIF1α inhibitor, 2-methoxyestradiol (2-ME), inhibited the irradiation-induced EndMT via downregulation of HIF1α-dependent Smad signaling. In vivo, 2-ME inhibited the vascular EndMT, and decreased the collagen deposition associated with RIPF. Furthermore, HIF1α-related EndMT was observed also in human RIPF tissues.Conclusions: We provide the first evidence that an EndMT occurs in RIPF development and that the EndMT may be effectively inhibited by modulating vascular EC-specific hypoxic damage. Clin Cancer Res; 21(16); 3716–26. ©2015 AACR.

Supplementary Figures 1-12. Supplementary Figure 1. Effects of HSPB1, VEGFR1, or VEGFR2 knockdown on the EndMT in HPMECs. Supplementary Figure 2. Effects of HSPB1 knockdown or overexpression on EC-specific characteristics and Smad3 inhibitor on HSPB1 knockdown-induced EndMT. Supplementary Figure 3. HSPB1 deficiency-induced EndMT in human pulmonary artery ECs (HPAECs) and human umbilical vein ECs (HUVECs). Supplementary Figure 4. Analysis of radiation-induced cytokines in irradiated mice serum and the effects of fibrosis-related cytokines on HSPB1-deficient HPMECs. Supplementary Figure 5. The role of STAT3 phosphorylation on HSPB1-regulated EndMT. Supplementary Figure 6. Effects of endothelial HSPB1 overexpression or JAK2 inhibitor on radiation-induced lung fibrosis. Supplementary Figure 7. The effects of HSPB1 knockdown on the radiation-induced lung fibrosis. Supplementary Figure 8. The effects of conditioned medium (CM) from irradiated ECs on other cells. Supplementary Figure 9. The effects of endothelial HSPB1 overexpression on bleomycin-induced lung fibrosis. Supplementary Figure 10. HSPB1 knockdown-induced vascular damage and hemorrhage. Supplementary Figure 11. Effects of HSPB1 knockdown on tumor ECs and tumor cells isolated from lung adenocarcinomas from LSL-KrasG12D;Trp53fl/fl mice. Supplementary Figure 12. Effects of HSPB1 knockdown on tumor cells in lung adenocarcinomas from LSL-KrasG12D;Trp53fl/fl mice.

The endothelial-to-mesenchymal transition (EndMT) contributes to cancer, fibrosis, and other pathologic processes. However, the underlying mechanisms are poorly understood. Endothelial HSP1 (HSPB1) protects against cellular stress and has been implicated in cancer progression and pulmonary fibrosis. In this study, we investigated the role of HSPB1 in mediating the EndMT during the development of pulmonary fibrosis and lung cancer. HSPB1 silencing in human pulmonary endothelial cells accelerated emergence of the fibrotic phenotype after treatment with TGFβ or other cytokines linked to pulmonary fibrosis, suggesting that HSPB1 maintains endothelial cell identity. In mice, endothelial-specific overexpression of HSPB1 was sufficient to inhibit pulmonary fibrosis by blocking the EndMT. Conversely, HSPB1 depletion in a mouse model of lung tumorigenesis induced the EndMT. In clinical specimens of non–small cell lung cancer, HSPB1 expression was absent from tumor endothelial cells undergoing the EndMT. Our results showed that HSPB1 regulated the EndMT in lung fibrosis and cancer, suggesting that HSPB1-targeted therapeutic strategies may be applicable for treating an array of fibrotic diseases. Cancer Res; 76(5); 1019–30. ©2016 AACR.

Supplementary Materials and Methods

Supplementary Figure legends

Supplementary Table S1. Primers information for Reverse transcription (RT)-PCR

This study discussed application of a machine learning approach (Support vector machine, SVM) for the automatic cognition of gait changes due to scoliosis using gait measures: kinematic based on gait phase segmentation. The gaits of 18 controls and 24 scoliosis patients were recorded and analyzed using inertial measurement unit (IMU)-based systems during normal walking. Altogether, 72 gait features were extracted for developing gait recognition models. Cross-validation test results indicated that the performance of SVM was 90.5% to recognize scoliosis patients and controls gait patterns. When features were optimally selected, a feature selection algorithm could effectively distinguish the age groups with 95.2% accuracy. Applying the method that the previous test used, the severity of scoliosis was classified after clinician labeled the severity based on the Cobb angle. Test results indicated an accuracy of 81.0% by the SVM to recognize scoliosis severity gait patterns. Optimal selected features could effectively distinguish the scoliosis severity with 85.7% accuracy. When the measured features are ranked in order of high contribution, the abduction and adduction of left hip joint in the single support phase is most important in gait of patients with scoliosis. These results demonstrate considerable potential in applying SVMs in gait classification for medical applications.

There is increasing evidence that cancer contains cancer stem cells (CSCs) that are capable of regenerating a tumor following chemotherapy or radiotherapy. CD44 and CD133 are used to identify CSCs. This study investigated non-invasive in vivo monitoring of CD44-positive cancer stem-like cells in breast cancer by γ-irradiation using molecular image by fusing the firefly luciferase (fLuc) gene with the CD44 promoter. We generated a breast cancer cell line stably expressing fLuc gene by use of recombinant lentiviral vector controlled by CD44 promoter (MCF7-CL). Irradiated MCF7-CL spheres showed upregulated expression of CD44 and CD133, by immunofluorescence and flow cytometry. Also, gene expression levels of CSCs markers in irradiated spheres were clearly increased. CD44+ CSCs increased fLuc expression and tumor growth in vivo and in vitro. When MCF7-CL was treated with siCD44 and irradiated, CD44 expression was inhibited and cell survival ratio was decreased. MCF7-CL subsets were injected into the mice and irradiated by using a cobalt-60 source. Then, in vivo monitoring was performed to observe the bioluminescence imaging (BLI). When breast cancer was irradiated, relative BLI signal was increased, but tumor volume was decreased compared to non-irradiated tumor. These results indicate that increased CD44 expression, caused by general feature of CSCs by irradiation and sphere formation, can be monitored by using bioluminescence imaging. This system could be useful to evaluate CD44- expressed CSCs in breast cancer by BLI in vivo as well as in vitro for radiotherapy.

Signaling by small guanosine triphosphatases (GTPase), Rap1/Rac1, is one of the major pathways controlling cancer cell migration and tumor metastasis. Thymosin beta-4 (Tβ4), an actin-sequestering protein, has been shown to increase migration of cancer cells. Episodes of hypoxia and re-oxygenation (H/R) are an important phenomenon in tumor microenvironment (TME). We investigated whether Tβ4 could play as an intermediary to crosstalk between Rac1- and Rap1- GTPase activation under hypoxia/reoxygenation (H/R) conditions. Inhibition of Tβ4 expression using transcription activator-like effector nucleases (TALEN) significantly decreased lung metastasis of B16F10 cells. Rac1 and Rap1 activity, as well as cancer cell migration, increased following induction of Tβ4 expression in normoxia- or H/R-experienced cells, but were barely detectable in Tβ4-depleted cells. Rap1-regulated Rac1 activity was decreased by a dominant negative Rap1 (Rap1N17), and increased by 8-(4-chloro-phenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate (CPT), a Rap1 activator. In contrast, a Rac1-specific inhibitor, NSC23766, and dominant negative Rac1 (Rac1N17) enhanced Tβ4 expression and aberrant Rap1 activity. While NSC23766 and Rac1N17 incompletely inhibited tumor metastasis in vivo, and H/R-experienced cancer cell migration in vitro, more efficient attenuation of cancer cell migration was accomplished by simultaneous inactivation of Rap1 and Rac1 with Rap1N17 and Rac1N17, respectively. These data suggest that a combination therapy targeting both Rap1 and Rac1 activity may be an effective method of inhibiting tumor metastasis.

In this study, prototype ultra-thin fiber-optic dosimeters were fabricated using organic scintillators, wavelength shifting fibers, and plastic optical fibers. The sensor probes of the ultra-thin fiber-optic dosimeters consisted of very thin organic scintillators with thicknesses of 100, 150 and 200 μm. These types of sensors cannot only be used to measure skin or surface doses but also provide depth dose measurements with high spatial resolution. With the ultra-thin fiber-optic dosimeters, surface doses for gamma rays generated from a Co-60 therapy machine were measured. Additionally, percentage depth doses in the build-up regions were obtained by using the ultra-thin fiber-optic dosimeters, and the results were compared with those of external beam therapy films and a conventional fiber-optic dosimeter.

The need for human body posture robots has led researchers to develop dexterous design of exoskeleton robots. Quantitative techniques to assess human motor function and generate commands for robots were required to be developed. In this paper, we present a passivity based adaptive control algorithm for upper limb assist exoskeleton. The proposed algorithm can adapt to different subject parameters and provide efficient response against the biomechanical variations caused by subject variations. Furthermore, we have employed the Particle Swarm Optimization technique to tune the controller gains. Efficacy of the proposed algorithm method is experimentally demonstrated using a seven degree of freedom upper limb assist exoskeleton robot. The proposed algorithm was found to estimate the desired motion and assist accordingly. This algorithm in conjunction with an upper limb assist exoskeleton robot may be very useful for elderly people to perform daily tasks.

The accuracy of deformable image registration (DIR) has a significant dosimetric impact in radiationtreatment planning. Many groups have studied the accuracy of DIR. In this study, we evaluatedthe accuracy of various DIR algorithms by using variations of the deformation point and volume.The reference image (Iref) and volume (Vref) were first generated by using virtual deformation QAsoftware (ImSimQA, Oncology System Limited, UK). We deformed Iref with axial movement of thedeformation point and Vref, depending on the type of deformation (relaxation and contraction) inImSimQA software. The deformed image (Idef) and volume (Vdef) acquired by using the ImSimQAsoftware were inversely deformed relative to Iref and Vref by using DIR algorithms. As a result,we acquired a deformed image (Iid) from Idef and volume (Vid) from Vref. Four intensity-basedalgorithms were tested by following the horn-schunk optical flow (HS), iterative optical flow (IOF),modified demons (MD) and fast demons (FD) with the Deformable Image Registration and AdaptiveRadiotherapy Toolkit (DIRART) of MATLAB. The image similarity between Iref and Iid wascalculated to evaluate the accuracy of DIR algorithms using by Normalized Mutual Information(NMI) and Normalized Cross Correlation (NCC) metrics, when the distance of point deformationwas moved 4 mm, the value of NMI was above 1.81 and that of NCC was above 0.99 in all DIRalgorithms. As the degree of deformation was increased, the degree of image similarity decreased.When the Vref was increased or decreased by about 12%, the difference between Vref and Vid waswithin ±5% regardless of the type of deformation, the deformation was classified into two types:deformation 1 increased the Vref (relaxation) and deformation 2 decreased the Vref (contraction).The value of the Dice Similarity Coefficient (DSC) was above 0.95 in deformation 1 except for theMD algorithm. In the case of deformation 2, the value of the DSC was above 0.95 in all DIR algorithms.The Idef and the Vdef were not completely restored to Iref and Vref, and the accuracy ofthe DIR algorithms were different, depending on the degree of deformation. Hence, the performanceof DIR algorithms should be verified for the desired applications

The aim of this study is to determine the ion recombination correction factor for a liquid ionization chamber in a high energy photon beam by using our experimental method. The ion recombination correction factors were determined by using our experimental method and were compared with theoretical and experimental methods proposed by using the theoretical method (Greening, Johansson) and the two-dose rate method in a cobalt beam and a high energy photon beam. In order to apply the liquid ionization chamber in a reference and small field dosimetry, we acquired the absorbed dose to water correction coefficient, the beam quality correction factor, and the influence quantities for the microLion chamber according to the TRS-398 protocol and applied the results to a high energy photon beam used in clinical fields. As a result, our experimental method for ion recombination in a cobalt beam agreed with the results from the heoretical method (Greening theory) better than it did with the results from the two-dose rate method. For high energy photon beams, the two-dose rate and our experimental methods were in good agreement, less than 2% deviation, while the theoretical general collection efficiency (Johansson et al.) deviated greatly from the experimental values. When we applied the factors for the absorbed dose to water measurement, the absorbed dose to water for the microLion chamber was in good agreement, within 1%, compared with the values for the PTW 30013 chamber in 6 and 10 MV Clinac iX and 6 and 15 MV Oncor impression. With these results, not only can the microLion ionization chamber be used to measure the absorbed dose to water in a reference condition, it can also be used to a the chamber for small, non-standard field dosimetry.

// Jae-Wook Lee 1, * , Yun-Kyoung Ryu 1, * , Young-Hoon Ji 2 , Joo Hyun Kang 3 , Eun-Yi Moon 1 1 Department of Bioscience and Biotechnology, Sejong University, Seoul 143–747, Korea 2 Research Center for Radiotherapy, Korea Institute of Radiological and Medical Science, Seoul 139–709, Korea 3 Molecular Imaging Research Center, Korea Institute of Radiological and Medical Science, Seoul 139–709, Korea * These authors have contributed equally to this work Correspondence to: Eun-Yi Moon, e-mail: eunyimoon@sejong.ac.kr , eunyimoon@gmail.com Keywords: thymosin beta-4, Rac1-GTPase, Rap1-GTPase, cancer cell migration, tumor metastasis Received: September 28, 2014 Accepted: January 26, 2015 Published: March 23, 2015 ABSTRACT Signaling by small guanosine triphosphatases (GTPase), Rap1/Rac1, is one of the major pathways controlling cancer cell migration and tumor metastasis. Thymosin beta-4 (Tβ4), an actin-sequestering protein, has been shown to increase migration of cancer cells. Episodes of hypoxia and re-oxygenation (H/R) are an important phenomenon in tumor microenvironment (TME). We investigated whether Tβ4 could play as an intermediary to crosstalk between Rac1- and Rap1- GTPase activation under hypoxia/reoxygenation (H/R) conditions. Inhibition of Tβ4 expression using transcription activator-like effector nucleases (TALEN) significantly decreased lung metastasis of B16F10 cells. Rac1 and Rap1 activity, as well as cancer cell migration, increased following induction of Tβ4 expression in normoxia- or H/R-experienced cells, but were barely detectable in Tβ4-depleted cells. Rap1-regulated Rac1 activity was decreased by a dominant negative Rap1 (Rap1N17), and increased by 8-(4-chloro-phenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate (CPT), a Rap1 activator. In contrast, a Rac1-specific inhibitor, NSC23766, and dominant negative Rac1 (Rac1N17) enhanced Tβ4 expression and aberrant Rap1 activity. While NSC23766 and Rac1N17 incompletely inhibited tumor metastasis in vivo , and H/R-experienced cancer cell migration in vitro , more efficient attenuation of cancer cell migration was accomplished by simultaneous inactivation of Rap1 and Rac1 with Rap1N17 and Rac1N17, respectively. These data suggest that a combination therapy targeting both Rap1 and Rac1 activity may be an effective method of inhibiting tumor metastasis.

Mesenchymal stem cells (MSCs), which are multipotent and have self-renewal ability, support the regeneration of damaged normal tissue. A number of external stimuli promote migration of MSCs into peripheral blood and support their participation in wound healing. In an attempt to harness the potential beneficial effects of such external stimuli, we exposed human MSCs (hMSCs) to one such stimulus—low-dose ionizing radiation (LDIR)—and examined their biological properties. To this end, we evaluated differences in proliferation, cell cycle, DNA damage, expression of surface markers (CD29, CD34, CD90, and CD105), and differentiation potential of hMSCs before and after irradiation with γ-rays generated using a 137CS irradiator. At doses less than 50 mGy, LDIR had no significant effect on the viability or apoptosis of hMSCs. Interestingly, 10 mGy of LDIR increased hMSC viability by 8% (p

In this study, a wavelength shifting fiber that shifts ultra-violet and blue light to green light was employed as a sensor probe of a fiber-optic Cerenkov radiation sensor. In order to characterize Cerenkov radiation generated in the developed wavelength shifting fiber and a plastic optical fiber, spectra and intensities of Cerenkov radiation were measured with a spectrometer. The spectral peaks of light outputs from the wavelength shifting fiber and the plastic optical fiber were measured at wavelengths of 500 and 510 nm, respectively, and the intensity of transmitted light output of the wavelength shifting fiber was 22.2 times higher than that of the plastic optical fiber. Also, electron fluxes and total energy depositions of gamma-ray beams generated from a Co-60 therapy unit were calculated according to water depths using the Monte Carlo N-particle transport code. The relationship between the fluxes of electrons over the Cerenkov threshold energy and the energy depositions of gamma-ray beams from the Co-60 unit is a near-identity function. Finally, percentage depth doses for the gamma-ray beams were obtained using the fiber-optic Cerenkov radiation sensor, and the results were compared with those obtained by an ionization chamber. The average dose difference between the results of the fiber-optic Cerenkov radiation sensor and those of the ionization chamber was about 2.09%.

Recently, in tissue engineering, ionizing radiation has been used as stimulation. Especially, several studies showed that low-dose ionizing radiation induced the stimulation of cell proliferation. Also, it is reported that single low dose γ-irradiation for whole-body or lymphoid-organ significantly improved the spontaneous recovery. The purpose of this study is to investigate behavior and differentiation of human adipose tissue-derived stem cells (hASCs) and rabbit bone marrow stromal cells (rBMSCs) after low dose and high dose of γ-irradiation. Cells were irradiated with γ-rays of 1, 10, 100 mGy and 1 Gy. In addition, we investigated the effects on the osteogenic differentiation of γ-irradiation. PLLA scaffolds with 90% porosity and 300–500 μm pore size were fabricated and cells were seeded onto the scaffolds. After that, cell-scaffold construct were irradiated with 1 mGy and implanted subcutaneously in nude mice for up to 10 weeks. Specimens were harvested after 10 weeks and analyzed. In the results, p-H2AX/DAPI ratio increased with time while the p-H2X expression was not found all time point in control (no irradiation) group. But, in the group radiated with low γ-ray (1 mGy), the p-H2X expression almost did not appear similar with non-radiated group. However, in the osteogenic differentiation tests, the control group and the irradiated group revealed no significant difference. In conclusion, low dose γ-irradiation could be used as stimulation for tissue engineering using specific stem cells and consequently, this system will be useful for combination technology of radiation and cell therapy. However, further studies are needed for examining the general mechanism of the effects on the low dose irradiation for stem cells.

This work proposes the basic reference data of occupational dose management and statistical dose distribution with the classification of radiation work groups though analysis of occupational dose distribution. Data on occupational radiation exposure from medical and scientific usage of radiation in Korea Institute of Radiological and Medical Sciences for the years 2002-11 are presented and evaluated with the characteristic tendency of radiation working groups. The results of occupational radiation exposure were measured by personal dosemeters. The monitored occupational exposure dose data were evaluated according to the average effective dose and collective dose. The most annual average effective dose for all occupational radiation workers was under 1 mSv. Considering the dose distribution of each department, most overexposure workers worked in radiopharmaceutical product facilities, nuclear medicine department and radiation oncology department. In addition, no monitored workers were found to have received an occupational exposure over 50 mSv in single year or 100 mSv in this period. Although the trend of occupational exposure was controlled

The purpose of this study is to evaluate the availability of cone-beam computed tomography(CBCT) for gel dosimetry. The absorbed dose was analyzed by using intensity-modulated radiation therapy(IMRT) to irradiate several tumor shapes with a calculated dose and several tumor acquiring images with CBCT in order to verify the possibility of reading a dose on the polymer gel dosimeter by means of the CBCT image. The results were compared with those obtained using magnetic resonance imaging(MRI) and CT. The linear correlation coefficients at doses less than 10 Gy for the polymer gel dosimeter were 0.967, 0.933 and 0.985 for MRI, CT and CBCT, respectively. The dose profile was symmetric on the basis of the vertical axis in a circular shape, and the uniformity was 2.50% for the MRI and 8.73% for both the CT and the CBCT. In addition, the gradient in the MR image of the gel dosimeter irradiated in an H shape was 109.88 while the gradients of the CT and the CBCT were 71.95 and 14.62, respectively. Based on better image quality, the present study showed that CBCT dosimetry for IMRT could be restrictively performed using a normoxic polymethacrylic-acid gel dosimeter.

The purpose of this study was to determine the dependence of the dose distribution on the width of the respiratory gating window by using radiochromic Gafchromic EBT2 film. An in-house three-dimensional breathing simulator was used with a 4-s cycle and a 3-cm movement. The gamma index and the 50, 95, and 20–80% dose distributions were individually analyzed with regard to static, 100 (full motion), 60, 40, 30, 20, and 15% respiratory gating windows. In addition, dose differences based on the different extents of exposure were compared and analyzed along with total beam delivery time. Dose distributions became increasingly similar to the static value with decreasing respiratory gating window width. The extent differences from the static case for the low-dose region were not significant; neither were the extent differences for the high-dose region and 30, 20, and 15% gating windows (P = 0.388, 0.275, respectively). However, the 40% gating window showed a significant difference (P = 0.001). Moreover, the treatment time for the 30% gating window was reduced by more than half compared to that for the 15% gating window. Thus, the 30% window would be a reasonable choice for maximizing the range of the gating window while markedly decreasing the dose difference and the treatment time.

In this study, we characterized the Cerenkov radiation generated from optical fibers as fundamental research for the development of a fiber-optic Cerenkov radiation sensor to verify spent fuel. We measured the amount of Cerenkov radiation according to OH content and numerical aperture of the optical fiber. Also, we measured the Cerenkov radiation as functions of the length and the diameter of the optical fiber. As a result, the silica optical fibers with high numerical aperture and high OH content were efficient and stable for gathering the Cerenkov radiation generated in the optical fiber. Also, the intensity of the Cerenkov radiation generated in the optical fiber was proportional to the irradiated length and to the square of the irradiated diameter.

Although conventional clinical treatment with low LET (linear energy transfer) including gamma-ray and X-ray has been widely used for radiotherapy in various cancers, however, ineffective outcomes occur due to radioresistance caused by p53 mutation. High LET has become alternative since it is able to induce apoptosis regardless of p53 status. Indeed, the molecular mechanisms toward high LET have been suggested. Nevertheless, most studies have been done in monolayer culture system which cannot promptly represent solid tumor microenvironment. Here we applied in vivo mimic 3D spheroid to conduct microarray-based genomic expression and molecular signaling pathway analyses under neutron irradiation. As a result, 3D spheroid system was achieved using thermorevesible gel system. An effective apoptosis-inducible dose of neutron was determined by Acridine Orange (AO) staining in 3D spheroid. Differentially expressed genes in both unique and common responses to neutron were identified in the 3D spheroid compared to the monolayer cells. Total 95 and 169 genes were notably altered at transcription level toward neutron in monolayer and 3D spheroid system, respectively. Based on microarray data, putative apoptosis signaling was depicted using Pathway Studio software. In 3D-in vivo mimic model, the molecular networks interacted with ITGB1, MAP4K4, PAPPA, and SGK1 might be suggested as plausible molecular pathways. In conclusion, we demonstrate novel molecular signaling and corresponding targets of in vitro solid tumor following high LET exposure. This result might provide critical clues for clarification of neutron-induced apoptosis mechanism.

We aimed to evaluate the suitability of a glass dosimeter (GD) for high-energy photon and electron beams in experimental and clinical use, especially for radiation therapy. We examined the expanded dosimetric characteristics of GDs including dose linearity up to 500 Gy, uniformity among GD lots and for individual GDs, the angular dependence, and energy dependence of 4 therapeutic x-ray qualities. In addition, we measured the dosimetric features (dose linearity, uniformity, angular dependence, and energy dependence) of the GD for electron beams of 10 different electron energy qualities. All measurements with the exception of dose linearity for photon beam were performed in a water phantom. For high-energy photon beams, dose linearity has a linear relationship for a dose ranging from 1 to 500 Gy with the coefficient of determination; R 2 of 0.998. The uniformity of each GD of dose measurements was within ±0.5% for four GD lots and within ±1.2% for 80 GDs. In terms of the effects of photon beam angle, lower absorbed doses of within 1.0% were observed between 60° and 105° than at 90°. The GD energy dependence of 4 photon beam energy qualities was within ±2.0%. On the other hand, the result of the dose linearity for high-energy electron beams showed well fitted regression line with the coefficient of determination; R 2 of 0.999 between 6 and 20 MeV. The uniformity of GDs exposed to the nominal electron energies 6, 9, 12, 16, and 20 MeV was ±1.2%. In terms of the angular dependence to electron beams, absorbed doses were within 2.0% between 60° and 105° than at 90°. In evaluation of the energy dependence of the GD at nominal electron energies between 5 and 20 MeV, we obtained responses between 1.1% and 3.5% lower than that for a cobalt-60 beam. Our results show that GDs can be used as a detector for determining doses when a high-energy photon beam is used, and that it also has considerable potential for dose measurement of high-energy electron beam.

This study evaluated the performance of tissue equivalent polymer gel dosimetry as a tool for 3-dimensional dose quality assurance to using Magnetic Resonance Imaging (MRI) measure the dose characteristics of therapeutic radiation using and applying it to intensity modulated radiation therapy (IMRT). The polymer gel under normoxic conditions was synthesized using Gelatin, methyacrylic acid (MAA), hydroquinone (HQ) and tetrakis hydroxymethyl phosphonium chloride (THPC), and a polymer gel dosimeter was fabricated by placing the gel into each phantom appropriate for experimental use. The dose reaction experiment employed Co gamma-rays and a 6-MV photon beam with a dose range of 0 ∼ 14 Gy. The dose characteristics of the polymer gel were compared with those of an ion chamber, Gafchromic EBT2 film, by using MRI. The linear correlations coefficient for the polymer gel, the ion chamber and the film were r = 0.970, r = 0.999, and r = 0.972, respectively. The percentage depth doses at a depth of 50 mm were 85.8% and 84.6% for the polymer gel and the ion chamber, respectively, giving a difference of 1.2%. On the other hand, the percentage depth dose at the depth of 100 mm was 66.2% and 63.7% for the polymer gel and the ion chamber, respectively, indicating a 2.5% gap. The flatness and the symmetry of the gel dosimeter on the cross plane were 3.80% and 3.58%, respectively. The gel dosimeter was applied to an IMRT. The doses measured in the 100% dose domain of the therapeutic plan was 96.2%, 103.0%, and 100% for the axial, sagittal and coronal planes, respectively, highlighting the applicability of the gel dosimeter as a 3-dimensional dosimeter.

Cryptosporidium parvum is a waterborne protozoan parasite that is found intracellularly in host animals, including humans, and causes severe diarrhea, which can lead to the death of an immunocompromised individual. Previously, we found that this organism is highly radioresistant as it can productively infect mice after exposure to a 10-kGy dose of γ-radiation. To understand how C. parvum avoids radiation damage, we characterized its protein expression patterns 6, 24, and 48 h after a 10-kGy dose of γ-radiation using two-dimensional PAGE. The gels showed 10 silver-stained spots that increased or decreased in size following γ-irradiation. Five proteins contained in these spots were identified using MALDI-TOF MS peptide fingerprinting, and two of these showed an increase in expression after γ-irradiation. These proteins were identified by LC-MS/MS as proteasome subunit alpha type 4 (NTN hydrolase fold) and thioredoxin peroxidase-like protein. The roles of these two upregulated proteins as related to the radioresistance of C. parvum remain to be evaluated.

Overexpression of c-Myc represents the most frequently deregulated genetic event in cancer, and therefore c-Myc may represent a good molecular target for cancer therapy. The human lung carcinoma cell line, NCI-H1299, shows resistance to conventional cancer treatments, such as ionizing radiation (IR) and cisplatin, while the lung carcinoma cell line, NCI-H460, is sensitive to treatment with these agents. However, when treated with a chalcone compound [toluenesulfonylamido-chalcone, 4'-(p-toluene sulfonyl amino)-3,4-dihydroxy chalcone (TSHDC)], cell death was dramatically induced in NCI-H1299 cells as compared to NCI-H460 cells. TSHDC-mediated cytotoxicity was not dependent on the status of p53 and p21. However, TSHDC exerted increased c-Myc-dependent reactive oxygen species (ROS) production in NCI-H1299 cells in which c-Myc is overexpressed, while increased ROS production did not occur in A549 or NCI-H460 cells with a low c-Myc level. Several colon and brain cancer cells also showed a correlation between c-Myc expression and TSHDC-mediated increased cell death. Tumor regression by TSHDC was more dramatic in NCI-H1299 cells than NCI-H460 cells, when these cells were grafted to nude mice. However, in the case of IR and cisplatin, NCI-H460 cells were more sensitive than NCI-H1299 cells. From these results, c-Myc-mediated ROS production may be a good target for screening of novel cancer drugs and TSHDC might be a good candidate as a cancer drug, specifically in cancer cells that overexpress c-Myc.

A target-tracking radiation-therapy (RT) system that tracks the movement of a treatment target resulting from internal organ movement has been developed, and the system was evaluated for effectiveness. The developed radiation-therapy system determines the limit of the MLC (multileaf collimator) movement range with an acquired maximum displacement value of target movement during the radiotherapy planning stage and moves the MLC to continuously detect and synchronize the displacement of the abdominal by using a CCD camera monitoring system during real-time RT treatment. The system consists of a Co-60 teletherapy unit, an abdominal displacement detection system to correlate the movement of internal organs, and a MLC moving stage synchronized with the abdominal displacement. The effectiveness of the RT system was evaluated by analyzing the beam penumbra from the dose distribution on films (Gafchromic EBT) installed within a moving phantom. Penumbra widths (80%/20%) were measured for the nominal left (perpendicular to leaf motion) and right (parallel to leaf motion) directions of the x-axis and the y-axis for a fixed phantom and fixed MLC (3.3 mm/3.5 mm and 3.7 mm/3.1 mm), a moving phantom and a fixed MLC (9.0 mm/8.2 mm and 9.1 mm/8.8 mm), and a moving phantom and a moving MLC (3.7 mm/3.5 mm and 3.7 mm/3.8 mm). Percent area deviations of the 100% to 80% field of the maximum dose for the exposure condition of a fixed phantom and a fixed MLC were a relatively low value of 0.64% and a relatively high value of 15.04%, as compared to the values for a moving phantom and a fixed MLC and for a moving phantom and a moving MLC. With the method to move the MLC by passive synchronization with organ motion, the target-tracking radiation-therapy system was successfully implemented and was evaluated for performance. In future studies, various verification processes should be performed prior to the application of the system in a clinical situation.

The endothelial-to-mesenchymal transition (EndMT) contributes to cancer, fibrosis, and other pathologic processes. However, the underlying mechanisms are poorly understood. Endothelial HSP1 (HSPB1) protects against cellular stress and has been implicated in cancer progression and pulmonary fibrosis. In this study, we investigated the role of HSPB1 in mediating the EndMT during the development of pulmonary fibrosis and lung cancer. HSPB1 silencing in human pulmonary endothelial cells accelerated emergence of the fibrotic phenotype after treatment with TGFβ or other cytokines linked to pulmonary fibrosis, suggesting that HSPB1 maintains endothelial cell identity. In mice, endothelial-specific overexpression of HSPB1 was sufficient to inhibit pulmonary fibrosis by blocking the EndMT. Conversely, HSPB1 depletion in a mouse model of lung tumorigenesis induced the EndMT. In clinical specimens of non–small cell lung cancer, HSPB1 expression was absent from tumor endothelial cells undergoing the EndMT. Our results showed that HSPB1 regulated the EndMT in lung fibrosis and cancer, suggesting that HSPB1-targeted therapeutic strategies may be applicable for treating an array of fibrotic diseases. Cancer Res; 76(5); 1019–30. ©2016 AACR.

A computer code to calculate the trajectory of charged particles in a medium under external electric and magnetic fields was designed. Using this code, the trajectories considered the energy loss and the direction change of the primary particles determined by stopping power and Lorentz force respectively could be calculated. The results show the variation of trajectories as a function of kinetic energy and external fields. The code can be useful for finding the information about the enhancement of energy deposition in a medium irradiated by charged particle beam. Since only the energy loss and the direction change for primary particles are considered, there are errors in this calculation. However, the results can be applied to the study of dose enhancement in radiation therapy. More accurate calculations can be achieved by considering multiple scattering of primary particles and the effect of secondary particles.

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a late side effect of thoracic radiotherapy. The purpose of our study was to gain further insight into the development of RIPF. Experimental Design/Results: Here, we observed that irradiation of mouse lungs induced collagen deposition, particularly around blood vessels, in the early phase of RIPF. Such deposition subsequently became evident throughout the irradiated tissues. Accompanied by the collagen deposition, vascular EndMT (endothelial-to-mesenchymal transition) began to develop in the early phase of RIPF, before the appearance of EMT (epithelial-to-mesenchymal transition) of alveolar epithelial (AE) II cells in the substantive fibrotic phase. Concomitant with the EndMT, we detected vascular endothelial cell (EC)–specific hypoxic damage in the irradiated lung tissues. In human pulmonary artery endothelial cells (HPAEC), the radiation-induced EndMT via activation of TGFβ-R1/Smad signaling was dependent on HIF1α expression. A novel HIF1α inhibitor, 2-methoxyestradiol (2-ME), inhibited the irradiation-induced EndMT via downregulation of HIF1α-dependent Smad signaling. In vivo, 2-ME inhibited the vascular EndMT, and decreased the collagen deposition associated with RIPF. Furthermore, HIF1α-related EndMT was observed also in human RIPF tissues. Conclusions: We provide the first evidence that an EndMT occurs in RIPF development and that the EndMT may be effectively inhibited by modulating vascular EC-specific hypoxic damage. Clin Cancer Res; 21(16); 3716–26. ©2015 AACR.

The purpose of the present study was to elucidate whether premature senescence contributes to the outcome of radiotherapy (RT) and to validate senescence biomarkers in vitro and in vivo. Cultured human cancer cell lines and xenografted mice were exposed to single (SR; 2, 6 or 12 Gy) or fractionated radiation (FR; 3 x 2 Gy or 6 x 2 Gy), and premature senescence was assessed using senescence-associated β-galactosidase (SA-β-Gal) activity, hypophosphorylation of pRb and p21 accumulation. A variety of senescence-associated biomarkers including cathepsin D (CD), the eukaryotic translation elongation factors eEF1A1, eEF1B2, decoy receptor 2 and Dec1 were further validated in vivo or in vitro. We demonstrated the beneficial tumor suppressive role of ionizing radiation (IR)-induced premature senescence in vitro and in vivo. FR inhibited tumor growth via induction of premature senescence as effectively as an equivalent SR dose (≥6 Gy). In addition, CD and eEF1 were valuable biomarkers of cellular senescence in either SR- or RF-exposed carcinoma cells or xenograft mice. Our results suggest that 2 Gy of a conventional RT regime could achieve a better clinical outcome if premature senescence could be increased through an improved understanding of its molecular action mechanism.

Adaptive response induced by low dose γ-ray irradiation in human cervical carcinoma cells was examined. Cells were exposured to low dose of γ-ray (1 cGy) followed by high doses of γ-ray irradiation (0, 1, 2, 3, 5, 7 and 9 Gy for clonogenic assay or 1.5 Gy for micronucleus assay) with various time intervals. Survival fractions of cells in both low dose-irradiated and unirradiated groups were analyzed by clonogenic assay. Survival fractions of low dose-irradiated cells was higher than that of control group irradiated only with high dose γ-ray. The increase in cell survival was maximum when low and high dose irradiation time interval was 4 hr. Frequencies of micronuclei which is an indicative of chromosome aberration were also enumerated in both low dose-irradiated and unirradiated groups. In consistent with the result obtained from survival fractions analyzed by clonogenic assay, maximum reduction in frequencies of micronuclei was observed when low dose radiation was given 4 hr prior to high dose irradiation. These results demonstrate that low dose γ-ray irradiation induced adaptive response to subsequent high dose γ-ray irradiation in human cervical carcinoma cells. Our data suggest that one of the possible mechanisms of adaptive response induced by low dose radiation is the increase in repair of DNA double strand breaks in low dose radiation-adapted cells.

Purpose: A diagnostics Multileaf Collimator (MLC) was designed for diagnostic radiography dose reduction. Monte Carlo simulation was used to evaluate efficiency of shielding material for producing leaves of Multileaf collimator. Material & Methods: The general radiography unit (Rex-650R, Listem, Korea) was modeling with Monte Carlo simulation (MCNPX, LANL, USA) and we used SRS-78 program to calculate the energy spectrum of tube voltage (80, 100, 120 kVp). The shielding materials was SKD 11 alloy tool steel that is composed of 1.6% carbon(C), 0.4% silicon (Si), 0.6% manganese (Mn), 5% chromium (Cr), 1% molybdenum (Mo), and vanadium (V). The density of it was 7.89 g/m3. We simulated leafs diagnostic MLC using SKD 11 with general radiography unit. We calculated efficiency of diagnostic MLC using tally6 card of MCNPX depending on energy. Results: The diagnostic MLC consisted of 25 individual metal shielding leaves on both sides, with dimensions of 10 × 0.5 × 0.5 cm3. The leaves of MLC were controlled by motors positioned on both sides of the MLC. According to energy (tube voltage), the shielding efficiency of MLC in Monte Carlo simulation was 99% (80 kVp), 96% (100 kVp) and 93% (120 kVp). Conclusion: We certified efficiency of diagnostic MLC fabricated from SKD11 alloy tool steel. Based on the results, the diagnostic MLC was designed. We will make the diagnostic MLC for dose reduction of diagnostic radiography.

The purpose of this study was to assess the optimal gates number of each region using estimated internal motion. Internal motion has been demonstrated in lung and liver region of small animal by coated molecular sieve. We coated molecular sieve with Pluronic F-127 hydrogel for keeping the activity in the body. All PET studies were performed with a dedicated small animal PET scanner. Respiratory gating was operated the external trigger device synchronized with the list mode acquisition. The trigger signals were simultaneously reflected motion of heart and breathing. The list mode data were converted to sinogram gated 2∼16 bin. In PET image analysis for determining optimal gate number, count and SNR were measured from ROI in the target region. Horizontal and vertical FWHM were measured from line profile in each images. The motion compensation PET image for optimal gate number was confirmed by internal motion. The measured value of lung region showed high count (8.67), high SNR (3.25), and high FWHM (1.83) in 8 bin. In liver region, high count (2.09), high SNR (3.99), and high FWHM (2.23) were revealed in 9 bin. The artificial tumor evaluation study using molecular sieve is a method to assess accurately internal organ motion in the rodent. The gate number for motion correction should be set differently in accordance with the organ because motion level varies as each organ. The estimated internal motion will be a useful method for motion compensation modeling.

Purpose: To evaluate the suitability of the GD-301 glass dosimeter for in vivo dose verification in proton therapy. Methods and Materials: The glass dosimeter was analyzed for its dosimetrics characteristic in proton beam. Dosimeters were calibrated in a water phantom using a stairlike holder specially designed for this study. To determine the accuracy of the glass dosimeter in proton dose measurements, we compared the glass dosimeter and thermoluminescent dosimeter (TLD) dose measurements using a cylindrical phantom. We investigated the feasibility of the glass dosimeter for the measurement of dose distributions near the superficial region for proton therapy plans with a varying separation between the target volume and the surface of 6 patients. Results and Discussion: Uniformity was within 1.5%. The dose-response has good linearity. Dose-rate, fading, and energy dependence were found to be within 3%. The beam profile measured using the glass dosimeter was in good agreement with the profile obtained from the ionization chamber. Depth-dose distributions in nonmodulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3%, which was lower than those with the ionization chamber. In the phantom study, the difference of isocenter dose between the delivery dose calculated by the treatmentmore » planning system and that measured by the glass dosimeter was within 5%. With in vivo dosimetry, the calculated surface doses overestimated measurements by 4%-16% using glass dosimeter and TLD. Conclusion: It is recommended that bolus be added for these clinical cases. We also believe that the glass dosimeter has considerable potential for use with in vivo patient proton dosimetry.« less

Purpose The GD-301 radiophotoluminescent glass dosimeter system has recently become commercially available. The purpose of this study was to investigate the dosimetric characteristics (reproducibility, linearity, dose rate, fading, angular dependence, and depth–dose distribution) of this system for clinical dosimetry in a high-energy proton beam and to compare it with lithium fluoride TLD-100. Materials and methods The depth–dose distribution measured with the glass dosimeter was compared to those from GEANT4 Monte-Carlo simulation. All measurements were performed in a proton beam (IBA Proton Therapy System-Proteus 235) at the National Cancer Center in Korea. Dosimeters were irradiated in a water phantom using a stair-shaped holder specially designed for this study. Maximum height was 100 mm with 1 mm steps in each of ten-tiers. Results Reproducibility in the 200 MeV proton beam was within 1.5% for the glass dosimeter, and within 1.7% for TLD-chip responses. The glass dosimeter signal was linear as a function of applied dose in the range of 1–10 Gy. The dose rate dependence of both dosimeters was within 1.5%. The fading effect of the glass dosimeter was found to be within 1.6% for 6 months. Angular dependence of the glass dosimeter was measured to be approximately 1.3% for angles that were 80° from the beam axis using a cylindrical phantom. Depth–dose distributions in the non-modulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3.0% lower than those measured with the ionization chamber and simulation model using GEANT4 code. The Bragg peak depths determined from the ionization chamber, the glass dosimeter and GEANT4 simulation were 84.8 mm, 84.2 mm and 85.0 mm, respectively. For the modulated proton beam, the SOBP width between the 90% proximal and the distal dose levels as obtained from the glass dosimeter was 48.1 mm. The SOBP width measured with the ionization chamber was 52.2 mm. Conclusions Measurements comparing the glass dosimeter and TLD-100 dosimetric characteristics demonstrated the suitability of use of the glass dosimeter for dose measurement in high-energy proton beam therapy.

Aims and backgroundColorectal cancer (CRC) is one of the commonest malignant disorders and frequently associated with high expression of epidermal growth factor receptor (EGFR), resulting in advanced disease and a poor prognosis. In this study, we investigated the radiosensitizing effects of the selective EGFR inhibitor cetuximab in human CRC cell lines.MethodsFour human CRC cell lines, CaCo-2, HCT-8, LoVo, and WiDr, were treated with cetuximab and/or radiation. The effects on cell proliferation and viability were measured by MTT and annexin-V staining, and clonogenic survival assay. The in vivo effect on the growth of CRC xenografts was assessed in athymic nude mice.ResultsCetuximab in combination with radiation significantly inhibited the in vitro proliferation of CRC cells, with a concomitant increase in cell death, except in WiDr cells. Clonogenic survival assay confirmed that cetuximab worked as a radiosensitizer in three cetuximab-sensitivie CRC cells. However, no correlations were found between the radiosensitivity and EGFR expression level or mutation status of EGFR signaling molecules. In nude mice bearing CRC cell xenografts, cetuximab plus radiation significantly inhibited the tumor growth over either agent alone. Interestingly, the WiDr xenograft was also sensitive to cetuximab and/or radiation in vivo, suggesting host-mediated effects of cetuximab.ConclusionsCetuximab enhanced the radiosensitivity of CRC cells in vitro and efficiently inhibited xenograft tumor growth. This study provided a rationale for the clinical application of the selective EGFR inhibitor cetuximab in combination with radiation in CRC. Free full text available at www.tumorionline.it

The aim of this study was to improve quantitative assessment of rat myocardial infarct size using attenuation corrected PET polar map with gated CT image and MRI polarmap. The PET/CT images obtained with a small animal PET/CT scanner. Gating was realized with the help of an external trigger device. Contrast enhanced FLASH sequence MRI image was acquired with a 3-T clinical MRI using ECG triggering. The SUV PET image pixel size was percent variation was calculated anterior wall (ANT), septal wall (SEP), inferior wall (INF) and lateral wall (LAT) in polar map. Homogeneity was calculated no corrected PET (NC), attenuation corrected PET with CT image (AC-CT) and AC gated PET with gated CT image (gAC-gCT). TTC staining measures tissue viability used to evaluate real infarct size. The reference infarct size was defined by infarction area percentage of the total left myocardium. The infarct size for optimal size was repeated varying threshold values. The NC and AC-CT image percent variation of ANT, SEP, INF and LAT was −0.42%, 1.61%, −0.41% and −0.86% respectively. The gAC-gCT image percent variation of ANT, SEP, INF and LAT was 3.74% 1.21% 3.28% and 4.29% respectively. The gated CT AC gated PET polar map homogeneity was improved myocardial activity in anterior, inferior and lateral region. MRI based polar map with FLASH sequence at threshold lower 60% provide good result of infarct size measurement. Integrated myocardial analysis technology of high sensitive PET and high resolution MRI images may potentially facilitate the improvement of volume and attenuation correction information in cardiology.

Objective: Study aims include determination of nationwide structural characteristics of radiation oncology facilities, types of radiation therapy equipment, availability of human resources and trends and comparisons with previous surveys. Methods: An annual nationwide survey was conducted to collect the statistics of infrastructure since 1997. All requested questionnaires have been identical for 10 years. The questionnaires included status on basic radiation therapy facilities, human resources and radiation therapy equipment. Journal and statistical data reviews were performed to evaluate the structure of other countries. Results: Radiation oncology facilities have steadily increased for 10 years and reached 60 sites in 2006. Also a steady increase of 1.5 times for linear accelerators, 5.8 times for computed tomography simulators and 3.0 times for radiation treatment planning systems was noted. Meanwhile, cobalt-60 teletherapy units and hyperthermia equipment had steadily deceased for 10 years. The number of human resources has steadily increased for the past 10 years, especially for radiation therapy technologists. However, radiation therapy equipment and human resources per population are relatively low compared with advanced countries. Conclusions: This study will assist preparation of the administrative planning policy of radiation oncology and should be useful to indicate the direction of future development and educational training programs in Korea and possibly in other countries.

Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory.

To quantitatively assess of Gating Radiotherapy (GRT) system and Dynamic Tumor Tracking Radiotherapy (DTTRT) system using MLC developed at KIRAMS (Korea Institute of Radiological & Medical Sciences) and evaluate effectiveness and efficiency of beam delivery for the both RT system. DTTRT system resulted to same treatment effect compared with the GRT system controlled with the gating rate of 20%. However, when treat by applying lower gating rate for the GRT system, longer treatment time give inconvenience to patients and cause obstacle to effective utilization of the equipment. On the one hand, DTTRT system presents advantage to reduce treatment time and to achieve effective dose delivery.

The aim of this study was to reduce correlation error using goggle monitor during treatment radisurgery using CyberKnife system. We analyzed the correlation error during treatment radiosurgery without goggle monitor and with using goggle monitor. The correlation error for free breathing was form 0.215 mm to 9. Oil mm. However, using goggle monitor is from 0.239 mm to 8.376 mm. We commended to use goggle monitor which can biofeedback her respiratory cycle and shape to reduced correlation error during treatment radiosurgery

Objective: To investigate the clinical applications of stereotactic body radiation therapy (SBRT) using the CyberKnife system for pelvic recurrence from rectal cancer with a focus on survival and toxicity. Methods: Between 2002 and 2006, 23 patients with recurrent rectal cancer were treated with SBRT at our institution. The median follow-up was 31 months. Sites of recurrence were presacral in seven patients and the pelvic wall in 16. SBRT doses ranged from 30 to 51 Gy (median 39 Gy) and were delivered in three fractions. Response to treatment was assessed by computed tomography. Overall and local progression-free survival and toxicities were recorded. Results: Four-year overall survival and local control rates were 24.9 and 74.3%, respectively. No prognostic factor was found to affect patient survival or local progression. One patient developed a severe radiation-related toxicity, but recovered completely after treatment. Conclusions: SBRT for pelvic recurrence was found to be comparable with other modalities with respect to overall survival and complication rates. Further studies are needed to confirm these preliminary results.

72 This work was supported by Kyonggi University Research Grant 2013. Received 30 May 2016, Revised 3 June 2016, Accepted 4 June 2016 Correspondence: Soo-Il Kwon (sikwon@kyonggi.ac.kr) Tel: 82-31-249-9618, Fax: 82-31-253-1165 cc This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Characteristics of CCD Based Optical CT Scanner for Therapeutic Radiation Dosimetry