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The microdosimetric kinetic (MK) model underestimates the cell-survival fractions for high linear energy transfer (LET) and high dose irradiations. To address the issue, some researchers previously extended the MK model to the stochastic microdosimetric kinetic (SMK) model. In the SMK model, the radiation induced cell-survival fractions were estimated from the specific energies z d and z n absorbed by a microscopic subnuclear structure domain and a cell nucleus, respectively. By taking the stochastic nature of z n as well as that of z d into account, the SMK model could reproduce the measured cell-survival fractions for radiations with wide LET and dose ranges. However, treatment planning based on the SMK model was unrealistic in clinical practice due to its long computation time and huge memory space required for the computation. In this study, we modified the SMK model to shorten the computation time and to reduce the memory space required for the computation. By using the dose-averaged cell-nucleus specific energy per event [Formula: see text] in the SMK formalism, the stochastic nature of z n was reflected onto the estimated cell-survival fractions. The accuracy of the modified SMK model was examined through the comparison between the estimated and the measured survival fractions of human salivary gland tumor cells and V79 cells. We then implemented the modified SMK model into the in-house treatment planning software for scanned charged-particle therapy to validate its applicability in clinical practice. As examples, treatment plans of helium-, carbon-, and neon-ion beams were made for an orbital tumor case. The modified SMK model could reproduce the measured cell-survival fractions more accurately compared to the MK model especially for high-LET and high-dose irradiations. In summary, the modified SMK model offers the accuracy and simplicity required in treatment planning of scanned charged-particle therapy for wide LET and dose ranges.

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth‐dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high‐bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L‐shaped bolus. The dose reproducibility, angular dependence and depth‐dose response were evaluated using a 190 MeV proton beam. Depth‐output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose‐weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L‐shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors.PACS number: 87.56.‐v

The effects of the charged ion species 4He, 12C and 20Ne on glioblastoma multiforme (GBM) T98G, U87 and LN18 cell lines were compared with the effects of 200 kVp X-rays (1.7 keV/μm). These cell lines have different genetic profiles. Individual GBM relative biological effectiveness (RBE) was estimated in two ways: the RBE10 at 10% survival fraction and the RBE2Gy after 2 Gy doses. The linear quadratic model radiosensitivity parameters α and β and the α/β ratio of each ion type were determined as a function of LET. Mono-energetic 4He, 12C and 20Ne ions were generated by the Heavy Ion Medical Accelerator at the National Institute of Radiological Sciences in Chiba, Japan. Colony-formation assays were used to evaluate the survival fractions. The LET of the various ions used ranged from 2.3 to 100 keV/μm (covering the depth-dose plateau region to clinically relevant LET at the Bragg peak). For U87 and LN18, the RBE10 increased with LET and peaked at 85 keV/μm, whereas T98G peaked at 100 keV/μm. All three GBM α parameters peaked at 100 keV/μm. There is a statistically significant difference between the three GBM RBE10 values, except at 100 keV/μm (P < 0.01), and a statistically significant difference between the α values of the GBM cell lines, except at 85 and 100 keV/μm. The biological response varied depending on the GBM cell lines and on the ions used.

Background: Observational clinical studies have demonstrated that there is a U‐shaped relationship between ethanol consumption and all‐cause mortality or risk of ischemic stroke. Although the exact cause of the U‐shaped relationship is unclear, the pharmacokinetics of ethanol during the time course of chronic intake of ethanol may be involved, in relation to its cardiotoxic effects. The present study has assessed the cause of the U‐shaped relationship between the ethanol consumption and left ventricular (LV) systolic dysfunction in a pharmacokinetic way.Methods: Male Wistar rats were paired, and either ethanol or control liquid diet was chronically administered for 7 weeks. Then, these rats were subdivided into 3 groups: control liquid‐diet‐fed rats [EtOH (−)], 3 g/dL ethanol liquid‐diet‐fed rats (3%EtOH), and 5 g/dL ethanol liquid‐diet‐fed rats (5%EtOH). Ethanol's cardiotoxicity on LV systolic function was investigated by echocardiography. Ethanol concentration in blood, ethanol pharmacokinetics, and hepatic alcohol dehydrogenase (ADH) activity were evaluated simultaneously.Results: The 5%EtOH group revealed LV systolic dysfunction, associated with a higher ethanol concentration in blood, and lower hepatic ADH activity than the EtOH (−) group; however, the 3%EtOH group did not show LV systolic dysfunction. During the acute ethanol stress, LV systolic dysfunction appeared in both EtOH (−) and 5%EtOH groups, with a higher ethanol concentration in blood and lower hepatic ADH activity than the 3%EtOH group. The 3%EtOH group showed a higher ethanol washout rate, less time‐integral of ethanol concentration, and shorter mean residence time of ethanol in blood than the EtOH (−) or 5%EtOH group.Conclusions: The U‐shaped relationship between chronic ethanol consumption and LV systolic dysfunction may be closely related to the pharmacokinetic characteristics of ethanol in blood, which depends on the quantity of chronically drinking alcohol.

To summarize the results of treatment for sacral chordoma in Phase I-II and Phase II carbon ion radiotherapy trials for bone and soft-tissue sarcomas.We performed a retrospective analysis of 38 patients with medically unresectable sacral chordomas treated with the Heavy Ion Medical Accelerator in Chiba, Japan between 1996 and 2003. Of the 38 patients, 30 had not received previous treatment and 8 had locally recurrent tumor after previous resection. The applied carbon ion dose was 52.8-73.6 Gray equivalents (median, 70.4) in a total of 16 fixed fractions within 4 weeks.The median patient age was 66 years. The cranial tumor extension was S2 or greater in 31 patients. The median clinical target volume was 523 cm(3). The median follow-up period was 80 months. The 5-year overall survival rate was 86%, and the 5-year local control rate was 89%. After treatment, 27 of 30 patients with primary tumor remained ambulatory with or without supportive devices. Two patients experienced severe skin or soft-tissue complications requiring skin grafts.Carbon ion radiotherapy appears effective and safe in the treatment of patients with sacral chordoma and offers a promising alternative to surgery.

The paper describes the development of chemical modules simulating the prechemical and chemical stages of charged particle tracks in pure liquid water. These calculations are based on our physical track structure codes for electrons and ions (KURBUC, LEPHIST and LEAHIST) which provide the initial spatial distribution of H2O+, H2O* and subexcitation electrons at approximately 10(-15) s. We considered 11 species and 26 chemical reactions. A step-by-step Monte Carlo approach was adopted for the chemical stage between 10(-12) s and 10(-6) s. The chemistry codes enabled to simulate the non-homogeneous chemistry that pertains to electron, proton and alpha-particle tracks of various linear energy transfers (LET). Time-dependent yields of chemical species produced by electrons and ions of different energies were calculated. The calculated primary yields (G values at 10(-6) s) of 2.80 for OH and 2.59 for e(aq)- for 1 MeV electrons are in good agreement with the published values. The calculated G values at 10(-6) s for a wide range LETs from of 0.2 to 235 keV microm(-1) were obtained. The calculations show the LET dependence for OH and H2O2. The electron penetration ranges were calculated in order to discuss the role of low energy electrons.

This study was conducted to develop a phase-space dataset in the International Atomic Energy Agency (IAEA) format for Monte Carlo (MC) simulations of the Leksell Gamma Knife® (LGK, Elekta Instrument AB, Stockholm, Sweden) Perfexion™ (PFX). An open-source MC code, namely, the Geant4 toolkit with a recently updated multi-threaded mode, was used to maximize the efficiency of the developed IAEA phase-space dataset. The absorbed dose profiles for single shots of the LGK PFX were calculated using the developed dataset and compared with those from radiochromic film measurements and Leksell GammaPlan® version 11.0.3 (LGP, Elekta Instruments) for verification. The mean relative absorbed dose differences in all single shots were less than 3.6% compared with the films and less than 4.0% compared with LGP. The collimator output factors were also calculated for all single shots and compared with the LGP results. The simulated collimator output factor was 0.816 ± 0.003 for a 4-mm shot and 0.903 ± 0.001 for an 8-mm shot in a spherical water phantom. The efficiency of the developed dataset was evaluated by comparing the times required for various simulations. Simulations with the phase-space dataset ran 25, 8.2 and 3.2 times faster than simulations without the phase-space dataset for 4-, 8-, and 16-mm shots, respectively. Using the dataset developed in this study, MC simulations of the LGK PFX can be performed more efficiently for various purposes, such as treatment plan verification and beam quality factor calculations.