Analysis of Predictive Factors for Lung Injury after Forward-Planned Intensity-Modulated Radiotherapy in Whole Breast Irradiation / 한국유방암학회지

PURPOSE: This study was performed to assess frequency, timings of occurrence, and predictors of radiologic lung damage (RLD) after forward-planned intensity-modulated radiotherapy (FIMRT) for whole breast irradiation. METHODS: We retrospectively reviewed medical records of 157 breast cancer patients and each of their serial chest computed tomography (CT) taken 4, 10, 16, and 22 months after completion of breast radiotherapy (RT). FIMRT was administered to whole breast only (n=152), or whole breast and supraclavicular regions (n=5). Dosimetric parameters, such as mean lung dose and lung volume receiving more than 10 to 50 Gy (V10-V50), and clinical parameters were analyzed in relation to radiologic lung damage. RESULTS: In total, 104 patients (66.2%) developed RLD after whole breast FIMRT. Among the cases of RLD, 84.7% were detected at 4 months, and 15.3% at 10 months after completion of RT. More patients of 47 or younger were found to have RLD at 10 months after RT than patients older than the age (11.7% vs. 2.9%, p=0.01). In univariate and multivariate analyses, age >47 and V40 >7.2% were significant predictors for higher risk of RLD. CONCLUSION: RLD were not infrequently detected in follow-up CT after whole breast FIMRT. More detected cases of RLD among younger patients are believed to have developed at later points after RT than those of older patients. Age and V40 were significant predictors for RLD after whole breast intensity-modulated radiotherapy.

Dose Verification Study of Brachytherapy Plans Using Monte Carlo Methods and CT Images / 의학물리

Most brachytherapy treatment planning systems employ a dosimetry formalism based on the AAPM TG-43 report which does not appropriately consider tissue heterogeneity. In this study we aimed to set up a simple Monte Carlo-based intracavitary high-dose-rate brachytherapy (IC-HDRB) plan verification platform, focusing particularly on the robustness of the direct Monte Carlo dose calculation using material and density information derived from CT images. CT images of slab phantoms and a uterine cervical cancer patient were used for brachytherapy plans based on the Plato (Nucletron, Netherlands) brachytherapy planning system. Monte Carlo simulations were implemented using the parameters from the Plato system and compared with the EBT film dosimetry and conventional dose computations. EGSnrc based DOSXYZnrc code was used for Monte Carlo simulations. Each (192)Ir source of the afterloader was approximately modeled as a parallel-piped shape inside the converted CT data set whose voxel size was 2x2x2 mm3. Bracytherapy dose calculations based on the TG-43 showed good agreement with the Monte Carlo results in a homogeneous media whose density was close to water, but there were significant errors in high-density materials. For a patient case, A and B point dose differences were less than 3%, while the mean dose discrepancy was as much as 5%. Conventional dose computation methods might underdose the targets by not accounting for the effects of high-density materials. The proposed platform was shown to be feasible and to have good dose calculation accuracy. One should be careful when confirming the plan using a conventional brachytherapy dose computation method, and moreover, an independent dose verification system as developed in this study might be helpful.

Implementation and Evaluation of the Electron Arc Plan on a Commercial Treatment Planning System with a Pencil Beam Algorithm / 의학물리

Less execution of the electron arc treatment could in large part be attributed to the lack of an adequate planning system. Unlike most linear accelerators providing the electron arc mode, no commercial planning systems for the electron arc plan are available at this time. In this work, with the expectation that an easily accessible planning system could promote electron arc therapy, a commercial planning system was commissioned and evaluated for the electron arc plan. For the electron arc plan with use of a Varian 21-EX, Pinnacle3 (ver. 7.4f), with an electron pencil beam algorithm, was commissioned in which the arc consisted of multiple static fields with a fixed beam opening. Film dosimetry and point measurements were executed for the evaluation of the computation. Beam modeling was not satisfactory with the calculation of lateral profiles. Contrary to good agreement within 1% of the calculated and measured depth profiles, the calculated lateral profiles showed underestimation compared with measurements, such that the distance-to-agreement (DTA) was 5.1 mm at a 50% dose level for 6 MeV and 6.7 mm for 12 MeV with similar results for the measured depths. Point and film measurements for the humanoid phantom revealed that the delivered dose was more than the calculation by approximately 10%. The electron arc plan, based on the pencil beam algorithm, provides qualitative information for the dose distribution. Dose verification before the treatment should be mandatory.

Error Analysis of Delivered Dose Reconstruction Using Cone-beam CT and MLC Log Data / 의학물리

We aimed to setup an adaptive radiation therapy platform using cone-beam CT (CBCT) and multileaf collimator (MLC) log data and also intended to analyze a trend of dose calculation errors during the procedure based on a phantom study. We took CT and CBCT images of Catphan-600 (The Phantom Laboratory, USA) phantom, and made a simple step-and-shoot intensity-modulated radiation therapy (IMRT) plan based on the CT. Original plan doses were recalculated based on the CT (CTplan) and the CBCT (CBCTplan). Delivered monitor unit weights and leaves-positions during beam delivery for each MLC segment were extracted from the MLC log data then we reconstructed delivered doses based on the CT (CTrecon) and CBCT (CBCTrecon) respectively using the extracted information. Dose calculation errors were evaluated by two-dimensional dose discrepancies (CTplan was the benchmark), gamma index and dose-volume histograms (DVHs). From the dose differences and DVHs, it was estimated that the delivered dose was slightly greater than the planned dose; however, it was insignificant. Gamma index result showed that dose calculation error on CBCT using planned or reconstructed data were relatively greater than CT based calculation. In addition, there were significant discrepancies on the edge of each beam while those were less than errors due to inconsistency of CT and CBCT. CBCTrecon showed coupled effects of above two kinds of errors; however, total error was decreased even though overall uncertainty for the evaluation of delivered dose on the CBCT was increased. Therefore, it is necessary to evaluate dose calculation errors separately as a setup error, dose calculation error due to CBCT image quality and reconstructed dose error which is actually what we want to know.

Estimation of Jaw and MLC Transmission Factor Obtained by the Auto-modeling Process in the Pinnacle3 Treatment Planning System / 의학물리

Radiation treatment techniques using photon beam such as three-dimensional conformal radiation therapy (3D-CRT) as well as intensity modulated radiotherapy treatment (IMRT) demand accurate dose calculation in order to increase target coverage and spare healthy tissue. Both jaw collimator and multi-leaf collimators (MLCs) for photon beams have been used to achieve such goals. In the Pinnacle3 treatment planning system (TPS), which we are using in our clinics, a set of model parameters like jaw collimator transmission factor (JTF) and MLC transmission factor (MLCTF) are determined from the measured data because it is using a model-based photon dose algorithm. However, model parameters obtained by this auto-modeling process can be different from those by direct measurement, which can have a dosimetric effect on the dose distribution. In this paper we estimated JTF and MLCTF obtained by the auto-modeling process in the Pinnacle3 TPS. At first, we obtained JTF and MLCTF by direct measurement, which were the ratio of the output at the reference depth under the closed jaw collimator (MLCs for MLCTF) to that at the same depth with the field size 10x10 cm2 in the water phantom. And then JTF and MLCTF were also obtained by auto-modeling process. And we evaluated the dose difference through phantom and patient study in the 3D-CRT plan. For direct measurement, JTF was 0.001966 for 6 MV and 0.002971 for 10 MV, and MLCTF was 0.01657 for 6 MV and 0.01925 for 10 MV. On the other hand, for auto-modeling process, JTF was 0.001983 for 6 MV and 0.010431 for 10 MV, and MLCTF was 0.00188 for 6 MV and 0.00453 for 10 MV. JTF and MLCTF by direct measurement were very different from those by auto-modeling process and even more reasonable considering each beam quality of 6 MV and 10 MV. These different parameters affect the dose in the low-dose region. Since the wrong estimation of JTF and MLCTF can lead some dosimetric error, comparison of direct measurement and auto-modeling of JTF and MLCTF would be helpful during the beam commissioning.

Cone-beam Reconstruction using Limited EPID Projections for Seeds Localization / 의학물리

In this study, we describe the preliminary application for the delineation of a metal object using cone-beam reconstruction (CBR) based on limited electronic portal imaging device (EPID) projections. A typical Feldkamp, Davis and Kress (FDK) reconstruction algorithm accompanying the edge preserving smoothing filter was used as only a few projections are acquired for reconstruction. In a correlation study of the projection numbers, we found that the size of the seeds and their location depicted by these CBR images were almost identical. Limited views were used for CBR, and our method is inexpensive and competitive for use in clinical applications.

Evaluation of Geometric Correspondence of kV X-ray Images, Electric Portal Images and Digitally Reconstructed Radiographic Images / 의학물리

In this study we estimated a geometric correlation among digitally reconstructed radiographic image (DRRI), kV x-ray image (kVXI) from the On-Board Imager (OBI) and electric portal image (EPI). To verify geometric correspondence of DRRI, kVXI and EPI, specially designed phantom with indexed 6 ball bearings (BBs) were employed. After accurate setup of the phantom on a treatment couch using orthogonal EPIs, we acquired set of orthogonal kVXIs and EPIs then compared the absolute positions of the center of the BBs calculated at each phantom plane for kVXI and EPI respectively. We also checked matching result for obliquely incident beam (gantry angle of 315 degrees) after 2D-2D matching provided by OBI application. A reference EPI obtained after initial setup of the phantom was compared with 10 series of EPIs acquired after each 2D-2D matching. Imaginary setup errors were generated from -5 mm to 5 mm at each couch motion direction. Calculated positions of all center positions of the BBs at three different images were agreed with the actual points within a millimeter and each other. Calculated center positions of the BBs from the reference and obtained EPIs after 2D-2D matching agreed within a millimeter. We could tentatively conclude that the OBI system was mechanically quite reliable for image guided radiation therapy (IGRT) purpose.

A Monte Carlo Simulation for the Newly Developed Head-and-Neck IMRT Phantom: a Pilot Study / 의학물리

A head-and-neck phantom was designed in order to evaluate remotely the quality of the delivery dose of intensity modulated radiation therapy (IMRT) in each institution. The phantom is homogeneous or inhomogeneous by interchanging the phantom material with the substructure like an air or bone plug. Monte Carlo simulations were executed for one beam and three beams to the phantom and compared with ion chamber and thermoluminescent dosimeter (TLD) measurements of which readings were from two independent institutions. For single beam, the ion chamber results and the MC simulations agreed to within about 2%. TLDs agreed with the MC results to within 2% or 7% according to which institution read the TLDs. For three beams, the ion chamber results showed -5% maximum discrepancy and those of TLDs were +2~+3%. The accuracy of the TLD readings should be increased for the remote dose monitoring. MC simulations are a valuable tool to acquire the reliability of the measurements in developing a new phantom.

Development of an Automatic Seed Marker Registration Algorithm Using CT and kV X-ray Images / 대한방사선종양학회지

PURPOSE: The purpose of this study is to develop a practical method for determining accurate marker positions for prostate cancer radiotherapy using CT images and kV x-ray images obtained from the use of the on-board imager (OBI). MATERIALS AND METHODS: Three gold seed markers were implanted into the reference position inside a prostate gland by a urologist. Multiple digital image processing techniques were used to determine seed marker position and the center-of-mass (COM) technique was employed to determine a representative reference seed marker position. A setup discrepancy can be estimated by comparing a computed COMOBI with the reference COMCT. A proposed algorithm was applied to a seed phantom and to four prostate cancer patients with seed implants treated in our clinic. RESULTS: In the phantom study, the calculated COMCT and COMOBI agreed with COMactual within a millimeter. The algorithm also could localize each seed marker correctly and calculated COMCT and COMOBI for all CT and kV x-ray image sets, respectively. Discrepancies of setup errors between 2D-2D matching results using the OBI application and results using the proposed algorithm were less than one millimeter for each axis. The setup error of each patient was in the range of 0.1+/-2.7~1.8+/-6.6 mm in the AP direction, 0.8+/-1.6~2.0+/-2.7 mm in the SI direction and -0.9+/-1.5~2.8+/-3.0 mm in the lateral direction, even though the setup error was quite patient dependent. CONCLUSION: As it took less than 10 seconds to evaluate a setup discrepancy, it can be helpful to reduce the setup correction time while minimizing subjective factors that may be user dependent. However, the on-line correction process should be integrated into the treatment machine control system for a more reliable procedure.

Monte Carlo Photon and Electron Dose Calculation Time Reduction Using Local Least Square Denoising Filters / 의학물리

The Monte Carlo method cannot have been used for routine treatment planning because of heavy time consumption for the acceptable accuracy. Since calculation time is proportional to particle histories, we can save time by decreasing the number of histories. However, a small number of histories can cause serious uncertainties. In this study, we proposed Monte Carlo dose computation time and uncertainty reduction method using specially designed filters and adaptive denoising process. Proposed algorithm was applied to 6 MV photon and 21 MeV electron dose calculations in homogeneous and heterogeneous phantoms. Filtering time was negligible comparing to Monte Carlo simulation time. The accuracy was improved dramatically in all situations and the simulation of 1% to 10% number of histories of benchmark in photon and electron dose calculation showed the most beneficial result. The empirical reduction of necessary histories was about a factor of ten to fifty from the result.

Intracellular trafficking and metabolic turnover of yeast prepro-alpha-factor-SRIF precursors in GH3 cells

Chimeric genes coding for prepro region of yeast alpha-factor and anglerfish SRIF were expressed in rat GH3 cells to determine whether yeast signals could regulate hormone processing in mammalian cells. We report that nascent hybrid polypeptides were efficiently targeted to ER, where cleavage of signal peptides and core glycosylation occurred, and were localized mainly in Golgi. These data indicate that prepro region of yeast alpha-factor functions in sorting molecules to secretory pathway in mammalian cells. A hybrid construct with a mutated signal peptide underwent similar ER translocation, whereas such a mutation resulted in defective translocation in yeast (Cheong et al., 1997). This difference may be due to the differences in ER translocation between yeast and mammalian cells, i.e., posttranslational versus cotranslational translocation. Processing and secretion of metabolically labeled hybrid propeptides to mature SRIF peptides were assessed by HPLC. When pulse-labeled cells were chased for up to 2 h, intracellular propeptides disappeared with a half-life of approximately 25 min, showing that -68% of initially synthesized propeptides were secreted constitutively. About 22% of SRIF-related products were proteolytically processed to mature SRIF, of which 38.7% were stored intracellularly with a half-life of - 2 h. In addition, immunocytochemical localization showed that a small proportion of SRIF molecules accumulated in secretory vesicles. All these results suggest that yeast prepropeptide could direct hybrid precursors to translocate into ER lumen and transit through secretory pathway to the distal elements of Golgi compartment, but could process and target it less efficiently to downstream in rat endocrine cells.

Intracellular trafficking and metabolic turnover of yeast prepro-alpha-factor-SRIF precursors in GH3 cells

Chimeric genes coding for prepro region of yeast alpha-factor and anglerfish SRIF were expressed in rat GH3 cells to determine whether yeast signals could regulate hormone processing in mammalian cells. We report that nascent hybrid polypeptides were efficiently targeted to ER, where cleavage of signal peptides and core glycosylation occurred, and were localized mainly in Golgi. These data indicate that prepro region of yeast alpha-factor functions in sorting molecules to secretory pathway in mammalian cells. A hybrid construct with a mutated signal peptide underwent similar ER translocation, whereas such a mutation resulted in defective translocation in yeast (Cheong et al., 1997). This difference may be due to the differences in ER translocation between yeast and mammalian cells, i.e., posttranslational versus cotranslational translocation. Processing and secretion of metabolically labeled hybrid propeptides to mature SRIF peptides were assessed by HPLC. When pulse-labeled cells were chased for up to 2 h, intracellular propeptides disappeared with a half-life of approximately 25 min, showing that -68% of initially synthesized propeptides were secreted constitutively. About 22% of SRIF-related products were proteolytically processed to mature SRIF, of which 38.7% were stored intracellularly with a half-life of - 2 h. In addition, immunocytochemical localization showed that a small proportion of SRIF molecules accumulated in secretory vesicles. All these results suggest that yeast prepropeptide could direct hybrid precursors to translocate into ER lumen and transit through secretory pathway to the distal elements of Golgi compartment, but could process and target it less efficiently to downstream in rat endocrine cells.