Explore the vast range of titles available.

Microdosimetry plays a critical role in particle therapy by quantifying energy deposition within microscopic domains to assess biological effects. This study evaluates the influence of different microdosimetric functions (MFs) and domain geometries (DGs) on relative biological effectiveness (RBE) predictions in carbon ion radiotherapy. Specifically, we compare the analytical microdosimetric function (AMF), calculated for spherical domains and implemented in PHITS, with the Kiefer–Chatterjee (KC) track structure model, which is conventionally applied to cylindrical geometries. To enable a direct comparison, we also introduce a novel implementation of the KC model for spherical domains. Using both models, specific energy distributions were calculated across a range of domain sizes and geometries. These distributions were input into the modified microdosimetric kinetic model (mMKM) to calculate RBE for the HSG cell line and compared against published in vitro data. The results show that both microdosimetric function and domain geometry significantly affect microdosimetric spectra and the resulting RBE, with deviations exceeding 10% when fixed mMKM parameters are used. Parameter optimization within the mMKM enables alignment across models. Our findings emphasize that microdosimetric function and domain geometry selection must be explicitly accounted for in microdosimetry-based RBE modeling, and that model parameters must be tuned accordingly to ensure consistent and biologically accurate predictions.

Background Cell-free and concentrated ascites reinfusion therapy (CART) is a strategy for improving various intractable symptoms due to refractory ascites, including hypoalbuminemia. CART has recently been applied in the treatment of cancer patients. This study was performed to assess the safety of CART in a single cancer institute. Methods We retrospectively reviewed 233 CART procedures that were performed for 132 cancer patients in our institute. Results The median weight of ascites before and after concentration was 4,720 g and 490 g (median concentration rate, 10.0-fold), The median amounts of total protein and albumin were 64.0 g and 32.6 g (median recovery rates, 44.9% and 49.0%), respectively. Thirty-three adverse events (AEs) were observed in 22 (9.4%) of 233 procedures; 30 of these events occurred after reinfusion. The most common reinfusion-related AEs were fever (13 events) and chills (10 events). Univariate analyses revealed no significant relationships between the frequency of AEs and age, sex, appearance of ascites, weight of harvested and concentrated ascites, the ascites processing rate (filtration and concentration), weight of saline used for membrane cleaning, amount of calculated total protein for infusion, or prophylaxis against AEs; the reinfusion rate of ≥ 125 mL/h or ≥ 10.9 g/h of total protein affected the frequency of AEs, regardless of the prophylactic use of steroids. Conclusions The observed AEs were mainly mild reactions after reinfusion, which were related to a reinfusion rate of volume ≥ 125 mL/h, a simple indicator in practice, or total protein ≥ 10.9 g/h. Although our study was retrospective in nature and undertaken in a single institute, this information may be helpful for the management of cancer patients with refractory malignant ascites using CART.

Kase, Y., Kanai, T., Matsumoto, Y., Furusawa, Y., Okamoto, H., Asaba, T., Sakama, M. and Shinoda, H. Microdosimetric Measurements and Estimation of Human Cell Survival for Heavy-Ion Beams. Radiat. Res. 166, 629–638 (2006). The microdosimetric spectra for high-energy beams of photons and proton, helium, carbon, neon, silicon and iron ions (LET = 0.5–880 keV/μm) were measured with a spherical-walled tissue-equivalent proportional counter at various depths in a plastic phantom. Survival curves for human tumor cells were also obtained under the same conditions. Then the survival curves were compared with those estimated by a microdosimetric model based on the spectra and the biological parameters for each cell line. The estimated α terms of the liner-quadratic model with a fixed β value reproduced the experimental results for cell irradiation for ion beams with LETs of less than 450 keV/μm, except in the region near the distal peak.

Our cell survival data showed the obvious dependence of RBE on photon energy: The RBE value for 200 kV X-rays was approximately 10% greater than those for mega-voltage photon beams. In radiation therapy using mega-voltage photon beams, the photon energy distribution outside the field is different with that in the radiation field because of a large number of low energy scattering photons. Hence, the RBE values outside the field become greater. To evaluate the increase in RBE, the method of deriving the RBE using the Microdosimetric Kinetic model (MK model) was proposed in this study. The MK model has two kinds of the parameters, tissue-specific parameters and the dose-mean lineal energy derived from the lineal energy distributions measured with a Tissue-Equivalent Proportional Counter (TEPC). The lineal energy distributions with the same geometries of the cell irradiations for 200 kV X-rays, 60Co γ-rays, and 6 MV X-rays were obtained with the TEPC and Monte Carlo code GEANT4. The measured lineal energy distribution for 200 kV X-rays was quite different from those for mega-voltage photon beams. The dose-mean lineal energy of 200 kV X-rays showed the greatest value, 4.51 keV/μm, comparing with 2.34 and 2.36 keV/μm for 60Co γ-rays and 6 MV X-rays, respectively. By using the results of the TEPC and cell irradiations, the tissue-specific parameters in the MK model were determined. As a result, the RBE of the photon beams (yD: 2～5 keV/μm) in arbitrary conditions can be derived by the measurements only or the calculations only of the dose-mean lineal energy.

Hirayama, R., Ito, A., Tomita, M., Tsukada, T., Yatagai, F., Noguchi, M., Matsumoto, Y., Kase, Y., Ando, K., Okayasu, R., and Furusawa, F. Contributions of Direct and Indirect Actions in Cell Killing by High-LET Radiations. Radiat. Res. 171, 212–218 (2009). The biological effects of radiation originate principally in damages to DNA. DNA damages by X rays as well as heavy ions are induced by a combination of direct and indirect actions. The contribution of indirect action in cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide (DMSO), which suppresses indirect action without affecting direct action. Exponentially growing Chinese hamster V79 cells were exposed to high-LET radiations of 20 to 2106 keV/μm in the presence or absence of DMSO and their survival was determined using a colony formation assay. The contribution of indirect action to cell killing decreased with increasing LET. However, the contribution did not reach zero even at very high LETs and was estimated to be 32% at an LET of 2106 keV/μm. Therefore, even though the radiochemically estimated G value of OH radicals was nearly zero at an LET of 1000 keV/μm, indirect action by OH radicals contributed to a substantial fraction of the biological effects of high-LET radiations. The RBE determined at a survival level of 10% increased with LET, reaching a maximum value of 2.88 at 200 keV/μm, and decreased thereafter. When the RBE was estimated separately for direct action (RBED) and indirect action (RBEI); both exhibited an LET dependence similar to that of the RBE, peaking at 200 keV/μm. However, the peak value was much higher for RBED (5.99) than RBEI (1.89). Thus direct action contributes more to the high RBE of high-LET radiations than indirect action does.

Intensity-modulated proton therapy (IMPT) is expected to improve treatment results with fewer side effects than other proton therapies. The purpose of this study was to evaluate the tumor sites for which IMPT was effective under the same beam calculation conditions by planning IMPT for typical cases treated with passive scattering proton therapy (PSPT). We selected 16 cases of nasal cavity, lung, liver or prostate cancers as typical tumor sites receiving PSPT. The dose distributions and dose volume histograms optimized by the IMPT were compared with those optimized by the PSPT. We took particular note of the doses to the skin and organs at risk (OAR) when PSPT was replaced by IMPT. Furthermore, an improvement of the beam angles was also performed to obtain better dose distributions in the IMPT. The IMPT with the same beam angles resulted in near-maximum doses to the skin of average 78%, 64%, 84% and 99% of the PSPT doses for nasal cavity, lung, liver, and prostate cancers, respectively. However, it was difficult to improve the dose homogeneity of the target volume. The change of the IMPT beam angles could reduce the doses to OARs and skin in the case of the nasal cavity, while it had limited effect in the other cases. We concluded that IMPT was effective for reducing the doses to some OARs when treating nasal cavity, lung, liver and prostate cancers. The selection of beam angles was important in the IMPT optimization, especially for nasal cavity cancers.

The authors attempt to establish the relative biological effectiveness (RBE) calculation for designing therapeutic proton beams on the basis of microdosimetry. The tissue-equivalent proportional counter (TEPC) was used to measure microdosimetric lineal energy spectra for proton beams at various depths in a water phantom. An RBE-weighted absorbed dose is defined as an absorbed dose multiplied by an RBE for cell death of human salivary gland (HSG) tumor cells in this study. The RBE values were calculated by a modified microdosimetric kinetic model using the biological parameters for HSG tumor cells. The calculated RBE distributions showed a gradual increase to about 1cm short of a beam range and a steep increase around the beam range for both the mono-energetic and spread-out Bragg peak (SOBP) proton beams. The calculated RBE values were partially compared with a biological experiment in which the HSG tumor cells were irradiated by the SOBP beam except around the distal end. The RBE-weighted absorbed dose distribution for the SOBP beam was derived from the measured spectra for the mono-energetic beam by a mixing calculation, and it was confirmed that it agreed well with that directly derived from the microdosimetric spectra measured in the SOBP beam. The absorbed dose distributions to planarize the RBE-weighted absorbed dose were calculated in consideration of the RBE dependence on the prescribed absorbed dose and cellular radio-sensitivity. The results show that the microdosimetric measurement for the mono-energetic proton beam is also useful for designing RBE-weighted absorbed dose distributions for range-modulated proton beams.

The RBE-weighted absorbed dose, called \"biological dose\", has been routinely used for carbon-ion treatment planning in Japan to formulate dose prescriptions for treatment protocols. This paper presents a microdosimetric approach to measuring the biological dose, which was redefined to be derived from microdosimetric quantities measured by a tissue-equivalent proportional counter (TEPC). The TEPC was calibrated in 60Co gamma rays to assure a traceability of the TEPC measurement to Japanese standards and to eliminate the discrepancies among matching counters. The absorbed doses measured by the TEPC were reasonably coincident with those measured by a reference ionization chamber. The RBE value was calculated from the microdosimetric spectrum on the basis of the microdosimetric kinetic model. The biological doses obtained by the TEPC were compared with those prescribed in the carbon-ion treatment planning system. We found that it was reasonable for the measured biological doses to decrease with depth around the rear SOBP region because of beam divergence, scattering effect, and fragmentation reaction. These results demonstrate that the TEPC can be an effective tool to assure the radiation quality in carbon-ion radiotherapy.

Cerebral radionecrosis is a significant side effect in radiotherapy for brain cancer. The purpose of this study is to calculate the relative biological effectiveness (RBE) of carbon-ion beams on brain cells and to show RBE-weighted dose distributions for cerebral radionecrosis speculation in a carbon-ion treatment planning system. The RBE value of the radionecrosis for the carbon-ion beam is calculated by the modified microdosimetric kinetic model on the assumption of a typical clinical α/β ratio of 2 Gy for cerebral radionecrosis in X-rays. This calculation method for the RBE-weighted dose is built into the treatment planning system for the carbon-ion radiotherapy. The RBE-weighted dose distributions are calculated on computed tomography (CT) images of four patients who had been treated by carbon-ion radiotherapy for astrocytoma (WHO grade 2) and who suffered from necrosis around the target areas. The necrotic areas were detected by brain scans via magnetic resonance imaging (MRI) after the treatment irradiation. The detected necrotic areas are easily found near high RBE-weighted dose regions. The visual comparison between the RBE-weighted dose distribution and the necrosis region indicates that the RBE-weighted dose distribution will be helpful information for the prediction of radionecrosis areas after carbon-ion radiotherapy.

Sato, T., Kase, Y., Watanabe, R., Niita, K. and Sihver, L. Biological Dose Estimation for Charged Particle Therapy Using an Improved PHITS Code Coupled with a Microdosimetric Kinetic Model. Radiat. Res. 171, 107–117 (2009). Microdosimetric quantities such as lineal energy, y, are better indexes for expressing the RBE of HZE particles in comparison to LET. However, the use of microdosimetric quantities in computational dosimetry is severely limited because of the difficulty in calculating their probability densities in macroscopic matter. We therefore improved the particle transport simulation code PHITS, providing it with the capability of estimating the microdosimetric probability densities in a macroscopic framework by incorporating a mathematical function that can instantaneously calculate the probability densities around the trajectory of HZE particles with a precision equivalent to that of a microscopic track-structure simulation. A new method for estimating biological dose, the product of physical dose and RBE, from charged-particle therapy was established using the improved PHITS coupled with a microdosimetric kinetic model. The accuracy of the biological dose estimated by this method was tested by comparing the calculated physical doses and RBE values with the corresponding data measured in a slab phantom irradiated with several kinds of HZE particles. The simulation technique established in this study will help to optimize the treatment planning of charged-particle therapy, thereby maximizing the therapeutic effect on tumors while minimizing unintended harmful effects on surrounding normal tissues.