Won-Gyun Jung

Zoledronic acid is an effective radiosensitizer in the treatment of osteosarcoma.

To overcome radioresistance in the treatment of osteosarcoma, a primary malignant tumor of the bone, radiotherapy is generally combined with radiosensitizers. The purpose of this study was to investigate a third-generation bisphosphonate, zoledronic acid (ZOL), as a radiosensitizer for osteosarcoma. We found that exposure of KHOS/NP osteosarcoma cells to 20 μM ZOL decreased the γ-radiation dose needed to kill 90% of cells. This radiosensitizing effect of ZOL was mediated through decreased mitochondrial membrane potential, increased levels of reactive oxygen species, increased DNA damage (as assessed by counting γ-H2AX foci), decreased abundance of proteins involved in DNA repair pathways (ATR, Rad52, and DNA-PKcs), and decreased phosphorylation of PI3K-Akt and MAPK pathway proteins (Raf1, MEK1/2, ERK1/2, and Akt), as compared to γ-irradiation alone. Cells treated with ZOL plus γ-irradiation showed impaired cell migration and invasion and reduced expression of epithelial-mesenchymal transition markers (vimentin, MMP9, and Slug). In Balb/c nude mice, the mean size of orthotopic osteosarcoma tumors 2 weeks post-inoculation was 195 mm3 following γ-irradiation (8 Gy), while it was 150 mm3 after γ-irradiation plus ZOL treatment (0.1 mg/kg twice weekly for 2 weeks). These results provide a rationale for combining ZOL with radiotherapy to treat osteosarcoma.

Metformin enhances the radiosensitivity of human liver cancer cells to γ–rays and carbon ion beams

The purpose of this study was to investigate the effect of metformin on the responses of hepatocellular carcinoma (HCC) cells to γ–rays (low-linear energy transfer (LET) radiation) and carbon-ion beams (high-LET radiation). HCC cells were pretreated with metformin and exposed to a single dose of γ–rays or carbon ion beams. Metformin treatment increased radiation-induced clonogenic cell death, DNA damage, and apoptosis. Carbon ion beams combined with metformin were more effective than carbon ion beams or γ-rays alone at inducing subG1 and decreasing G2/M arrest, reducing the expression of vimentin, enhancing phospho-AMPK expression, and suppressing phospho-mTOR and phospho-Akt. Thus, metformin effectively enhanced the therapeutic effect of radiation with a wide range of LET, in particular carbon ion beams and it may be useful for increasing the clinical efficacy of carbon ion beams.

Estimation of the medical need for carbon-ion radiotherapy in Korea

Abstract The Korea Heavy Ion Medical Accelerator project focuses on the development of medical accelerator facilities for delivering carbon-ion beams to cancer patients. The purpose of the present study was to estimate the clinical need for carbon-ion therapy in Korea. Seven tumor sites, namely head and neck, liver, lung, colon and rectum, prostate, bone and soft tissue, and pancreas were selected as eligible sites for receiving carbon-ion radiotherapy (RT) by radiation oncologists of the Korea Institute of Radiological and Medical Sciences. Cancer incidence data for the selected tumor sites were obtained from the Korea National Cancer Incidence Database in order to estimate the potential medical need for carbon-ion RT. The carbon-ion RT adaption rate was assessed based on the clinical experience of other carbon-ion therapy facilities. An estimation model was constructed for estimating the medical need for carbon-ion RT, and from this, 25 606 patients were deemed to be potential candidates for carbon-ion RT. This estimated potential need corresponded to 10% of newly diagnosed cancer patients in Korea. The realistic estimation was calculated as ranging between 4000 and 6300 patients, depending on the carbon-ion RT adaptation rate. This estimated medical need corresponded to 2–3% of newly diagnosed cancer patients in Korea. Taken together, our findings suggest that there is a clear medical need for carbon-ion RT in Korea, with at least 4000 potential patients per year.

Transient pulse analysis of ionized electronics exposed to γ-radiation generated from a relativistic electron beam

When a semiconductor element is irradiated with radiation in the form of a transient pulse emitted from a nuclear explosion, a large amount of charge is generated in a short time in the device. A photocurrent amplified in a certain direction by these types of charges cause the device to break down and malfunction or in extreme cases causes them to burn out. In this study, a pulse-type γ-ray generator based on a relativistic electron beam accelerator (γ=2.2, β=0.89) which functions by means of tungsten impingement was constructed and tested in an effort to investigate the process and effects of the photocurrent formed by electron hole pairs (EHP) generated in a pMOSFET device when a transient radiation pulse is incident in the device. The pulse-type γ-ray irradiating device used here to generate the electron beam current in a short time was devised to allow an increase in the irradiation dose. A precise signal processing circuit was constructed to measure the photocurrent of the small signal generated by t...

Analysis of Neutron Production in Passively Scattered Ion-Beam Therapy.

A new treatment facility for heavy ion therapy since 2010 was constructed. In the broad beam, a range shifter, ridge filter and multi leaf collimator (MLC) for the generation of the spread-out Bragg peak is used. In this case, secondary neutrons produced by the interactions of the ion field with beam-modifying devices (e.g. double-scattering system, beam shaping collimators and range compensators) are very important for patient safety. Therefore, these components must be carefully examined in the context of secondary neutron yield and associated secondary cancer risk. In this article, Monte Carlo simulation has been carried out with the FLUktuierende KAskade particle transport code, the fluence and distribution of neutron generation and the neutron dose equivalent from the broad beam components are compared using carbon and proton beams. As a result, it is confirmed that the yield of neutron production using a carbon beam from all components of the broad beam was higher than using a proton beam. The ambient dose by neutrons per heavy ion and proton ion from the MLC surface was 0.12-0.18 and 0.0067-0.0087 pSv, respectively, which shows that heavy ions generate more neutrons than protons. However, ambient dose per treatment 2 Gy, which means physical dose during treatment by ion beam, is higher than carbon beam because proton therapy needs more beam flux to make 2-Gy prescription dose. Therefore, the neutron production from the MLC, which is closed to the patient, is a very important parameter for patient safety.

SU-F-T-149: Development of the Monte Carlo Simulation Platform Using Geant4 for Designing Heavy Ion Therapy Beam Nozzle

PURPOSE The significant issue of particle therapy such as proton and carbon ion was a accurate dose delivery from beam line to patient. For designing the complex delivery system, Monte Carlo simulation can be used for the simulation of various physical interaction in scatters and filters. In this report, we present the development of Monte Carlo simulation platform to help design the prototype of particle therapy nozzle and performed the Monte Carlo simulation using Geant4. Also we show the prototype design of particle therapy beam nozzle for Korea Heavy Ion Medical Accelerator (KHIMA) project in Korea Institute of Radiological and Medical Science(KIRAMS) at Republic of Korea. METHODS We developed a simulation platform for particle therapy beam nozzle using Geant4. In this platform, the prototype nozzle design of Scanning system for carbon was simply designed. For comparison with theoretic beam optics, the beam profile on lateral distribution at isocenter is compared with Mont Carlo simulation result. From the result of this analysis, we can expected the beam spot property of KHIMA system and implement the spot size optimization for our spot scanning system. RESULTS For characteristics study of scanning system, various combination of the spot size from accerlator with ridge filter and beam monitor was tested as simple design for KHIMA dose delivery system. CONCLUSION In this report, we presented the part of simulation platform and the characteristics study. This study is now on-going in order to develop the simulation platform including the beam nozzle and the dose verification tool with treatment planning system. This will be presented as soon as it is become available.

Modeling the biophysical effects in a carbon beam delivery line by using Monte Carlo simulations

The Relative biological effectiveness (RBE) plays an important role in designing a uniform dose response for ion-beam therapy. In this study, the biological effectiveness of a carbon-ion beam delivery system was investigated using Monte Carlo simulations. A carbon-ion beam delivery line was designed for the Korea Heavy Ion Medical Accelerator (KHIMA) project. The GEANT4 simulation tool kit was used to simulate carbon-ion beam transport into media. An incident energy carbon-ion beam with energy in the range between 220 MeV/u and 290 MeV/u was chosen to generate secondary particles. The microdosimetric-kinetic (MK) model was applied to describe the RBE of 10% survival in human salivary-gland (HSG) cells. The RBE weighted dose was estimated as a function of the penetration depth in the water phantom along the incident beam’s direction. A biologically photon-equivalent Spread Out Bragg Peak (SOBP) was designed using the RBE-weighted absorbed dose. Finally, the RBE of mixed beams was predicted as a function of the depth in the water phantom.

SU-E-I-37: Low-Dose Real-Time Region-Of-Interest X-Ray Fluoroscopic Imaging with a GPU-Accelerated Spatially Different Bilateral Filtering

PURPOSE The purpose of our study is to reduce imaging radiation dose while maintaining image quality of region of interest (ROI) in X-ray fluoroscopy. A low-dose real-time ROI fluoroscopic imaging technique which includes graphics-processing-unit- (GPU-) accelerated image processing for brightness compensation and noise filtering was developed in this study. METHODS In our ROI fluoroscopic imaging, a copper filter is placed in front of the X-ray tube. The filter contains a round aperture to reduce radiation dose to outside of the aperture. To equalize the brightness difference between inner and outer ROI regions, brightness compensation was performed by use of a simple weighting method that applies selectively to the inner ROI, the outer ROI, and the boundary zone. A bilateral filtering was applied to the images to reduce relatively high noise in the outer ROI images. To speed up the calculation of our technique for real-time application, the GPU-acceleration was applied to the image processing algorithm. We performed a dosimetric measurement using an ion-chamber dosimeter to evaluate the amount of radiation dose reduction. The reduction of calculation time compared to a CPU-only computation was also measured, and the assessment of image quality in terms of image noise and spatial resolution was conducted. RESULTS More than 80% of dose was reduced by use of the ROI filter. The reduction rate depended on the thickness of the filter and the size of ROI aperture. The image noise outside the ROI was remarkably reduced by the bilateral filtering technique. The computation time for processing each frame image was reduced from 3.43 seconds with single CPU to 9.85 milliseconds with GPU-acceleration. CONCLUSION The proposed technique for X-ray fluoroscopy can substantially reduce imaging radiation dose to the patient while maintaining image quality particularly in the ROI region in real-time.

SU‐E‐J‐37: The Validation Tool for Compensation of Patient Positioning Error Using DRR Images

PURPOSE The present study was designed to develop the validation tool for compensation of patient positioning error using digitally reconstructed radiograph (DRR) extracted from three-dimensional computed tomography (3DCT) and two orthogonal kilo-voltage x-ray images. METHODS To generate DRR image from 3DCT, the ray casting which is most straightforward method was applied in this study. The traditional ray casting algorithm finds the intersections of a ray with all objects, voxels of the 3DCT volume in the scene, with nearest-neighbor interpolation method. Similarity between extracted DRR and orthogonal image was measured by using normalized mutual information method. All process was done by using Matlab. Two orthogonal image was acquired from Cyber-knife system from anterior-posterior view and right lateral view. 3DCT and two orthogonal image of an anthropomorphic Alderson-Rando phantom and head and neck cancer patient were applied in this study. Finally, we designed graphic user interface (GUI) for easy use. RESULTS Registration accuracy with average errors of 2.12 mm ± 0.5 mm for transformation and 1.23° ± 0.4° for rotation using an anthropomorphic Alderson-Rando phantom has been acquired. CONCLUSION We demonstrated that this validation tool could compensate the patient positioning error. For further study, with the developed validation GUI tool for compensation of patient positioning error, we will add the registration tool by manual/auto using cone-beam CT and kilo-voltage CT image to utilize clinically in heavy-ion radiation treatment center in Korea which scheduled for completion in 2016.

Development of a Beam Source Modeling Technique for a Flattening Filter Free (FFF) Beam

This study was focused on a new beam source modeling technique for a flattening filter free (FFF) beam. The model was based on a previous three source model, and improved by introducing off axis ratio (OAR) of photon fluence to the primary and scattered photon sources to generate cone shaped dose profiles. The model parameters and the OAR were optimized from measured head scatter factors and a dose profile with 40 x 40 cm2 field size by using line search optimization algorithm. The model was validated by comparing various dose profiles on 6 and 10 MV FFF beam from a True Beam STx linear accelerator. Planar dose distributions for clinically used radiation fields were also calculated and compared with measured data. All calculated dose profiles were agreed with the measured data within 1.5% for 6 MV FFF beam, and within 1% for 10 MV FFF beam. The calculated planar doses showed good passing rates (> 94%) at 3%/3 mm of gamma indexing criteria. This model expected to be easily applicable to any FFF beams for treatment planning systems because it only required measured PDD, dose profiles and output factors which were easily acquired during conventional beam commissioning process.