Preventive effect of fermented brown rice and rice bran on spontaneous type 1 diabetes in NOD female mice

Consumption of brown rice and rice bran fermented with Aspergillus oryzae (FBRA) suppresses spontaneously occurring diabetes in female NOD mouse. While control diet-fed mice showed glucosuria and hyperglycemia at around 20 week of age and the ratio reached to 57% at 30 weeks of age, the ratio did not increase in the 0.5% FBRA-containing diet-fed group. The FBRA-fed group at 30 weeks of age kept higher ratio of intact islets and showed significantly lower insulitis score compared to the control diet group, with dose-dependency from 0.25% to 0.5% dietary concentration of FBRA. The percentage of diabetic mice was significantly lower at 24 weeks of age as compared to the control group (p = 0.01, log rank test). These results indicate that the suppressive effects of dietary administration of 0.5% FBRA in delaying the spontaneous onset of diabetes in NOD mice is probably achieved by maintaining the number of intact islets

次世代型マルチ粒子線治療の臨床応用のための基盤研究

科学研究費助成事業 研究成果報告書：基盤研究(B)2015-2017課題番号 : 15H0490

Validation of the physical and RBE-weighted dose estimator based on PHITS coupled with a microdosimetric kinetic model for proton therapy

The microdosimetric kinetic model (MKM) is widely used for estimating relative biological effectiveness (RBE)-weighted doses for various radiotherapies because it can determine the surviving fraction of irradiated cells based on only the lineal energy distribution, and it is independent of the radiation type and ion species. However, the applicability of the method to proton therapy has not yet been investigated thoroughly. In this study, we validated the RBE-weighted dose calculated by the MKM in tandem with the Monte Carlo code PHITS for proton therapy by considering the complete simulation geometry of the clinical proton beam line. The physical dose, lineal energy distribution, and RBE-weighted dose for a 155 MeV mono-energetic and spread-out Bragg peak (SOBP) beam of 60 mm width were evaluated. In estimating the physical dose, the calculated depth dose distribution by irradiating the mono-energetic beam using PHITS was consistent with the data measured by a diode detector. A maximum difference of 3.1% in the depth distribution was observed for the SOBP beam. In the RBE-weighted dose validation, the calculated lineal energy distributions generally agreed well with the published measurement data. The calculated and measured RBE-weighted doses were in excellent agreement, except at the Bragg peak region of the mono-energetic beam, where the calculation overestimated the measured data by ~15%. This research has provided a computational microdosimetric approach based on a combination of PHITS and MKM for typical clinical proton beams. The developed RBE-estimator function has potential application in the treatment planning system for various radiotherapies

General ion recombination effect in a liquid ionization chamber in high-dose-rate pulsed photon and electron beams

Liquid ionization chambers (LICs) are highly sensitive to dose irradiation and have small perturbations because of their liquid-filled sensitive volume. They require a sensitive volume much smaller than conventional air-filled chambers. However, it has been reported that the collection efficiency has dependencies on the dose per pulse and the pulse repetition frequency of a pulsed beam. The purpose of this study was to evaluate in detail the dependency of the ion collection efficiency on the pulse repetition frequency. A microLion (PTW, Freiburg, Germany) LIC was exposed to photon and electron beams from a TrueBeam (Varian Medical Systems, Palo Alto, USA) linear accelerator. The pulse repetition frequency was varied, but the dose per pulse was fixed. A theoretical evaluation of the collection efficiency was performed based on Boag’s theory. Linear correlations were observed between the frequency and the relative collection for all energies of the photon and electron beams. The decrease in the collected charge was within 1% for all the flattened photon and electron beams, and they were 1.1 and 1.8% for the 6 and 10 MV flattening filter-free photon beams, respectively. The theoretical ion collection efficiency was 0.990 for a 10 MV flattened photon beam with a dose rate of 3 Gy·min−1. It is suggested that the collected charge decreased because of the short time intervals of the beam pulse compared with the ion collection time. Thus, it is important to correctly choose the pulse repetition frequency, particularly when flattening filter-free mode is used for absolute dose measurements

High-Energy X-Ray Compton Scattering Imaging of 18650-Type Lithium-Ion Battery Cell

High-energy synchrotron X-ray Compton scattering imaging was applied to a commercial 18650-type cell, which is a cylindrical lithium-ion battery in wide current use. By measuring the Compton scattering X-ray energy spectrum non-destructively, the lithiation state in both fresh and aged cells was obtained from two different regions of the cell, one near the outer casing and the other near the center of the cell. Our technique has the advantage that it can reveal the lithiation state with a micron-scale spatial resolution even in large cells. The present method enables us to monitor the operation of large-scale cells and can thus accelerate the development of advanced lithium-ion batteries

Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients

To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose-volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al. were calculated for the same patient. All the published dose-response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means +/- standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 +/- 0.52% (n = 7, P = 0.0021), (ii) 23.3 +/- 17.2% (n = 8, P = 0.0065), (iii) 16.6 +/- 19.9% (n = 8, P = 0.0497) and (iv) 50.0 +/- 21.1% (n = 3, P = 0.0274), respectively (one tailed t-test). The numbers needed to treat (NNT) were (i) 98.0, (ii) 4.3, (iii) 6.0 and (iv) 2.0 for WCNS, respectively. In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. Although a validation study is required, it is suggested that the LAR would be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques

3D‐printable lung phantom for distal falloff verification of proton Bragg peak

In proton therapy, the Bragg peak of a proton beam reportedly deteriorates when passing though heterogeneous structures such as human lungs. Previous studies have used heterogeneous random voxel phantoms, in which soft tissues and air are randomly allotted to render the phantoms the same density as human lungs, for conducting Monte Carlo (MC) simulations. However, measurements of these phantoms are complicated owing to their difficult‐to‐manufacture shape. In the present study, we used Voronoi tessellation to design a phantom that can be manufactured, and prepared a Voronoi lung phantom for which both measurement and MC calculations are possible. Our aim was to evaluate the effectiveness of this phantom as a new lung phantom for investigating proton beam Bragg peak deterioration. For this purpose, we measured and calculated the percentage depth dose and the distal falloff widths (DFW) passing through the phantom. For the 155 MeV beam, the measured and calculated DFW values with the Voronoi lung phantom were 0.40 and 0.39 cm, respectively. For the 200 MeV beam, the measured and calculated DFW values with the Voronoi lung phantom were both 0.48 cm. Our results indicate that both the measurements and MC calculations exhibited high reproducibility with plastinated lung sample from human body in previous studies. We found that better results were obtained using the Voronoi lung phantom than using other previous phantoms. The designed phantom may contribute significantly to the improvement of measurement precision. This study suggests that the Voronoi lung phantom is useful for simulating the effects of the heterogeneous structure of lungs on proton beam deterioration

Results of Proton Beam Therapy without Concurrent Chemotherapy for Patients with Unresectable Stage III Non-small Cell Lung Cancer

Introduction:This study was performed retrospectively to evaluate the outcome of patients with stage III non-small cell lung cancer (NSCLC) after proton beam therapy (PBT) alone.Methods:The subjects were 57 patients with histologically confirmed NSCLC (stage IIIA/IIIB: 24/33) who received PBT without concurrent chemotherapy. The cohort included 32 cases of squamous cell carcinoma, 18 adenocarcinoma, and 7 non-small cell carcinoma. Lymph node metastases were N0 7, N1 5, N2 30, and N3 15. Planned total doses ranged from 50 to 84.5 GyE (median, 74 GyE).Results:Planned treatment was completed in 51 patients (89%). At the time of analysis, 20 patients were alive, and the median follow-up periods were 16.2 months for all patients and 22.2 months for survivors. The median overall survival period was 21.3 months (95% confidence interval: 14.2–28.4 months), and the 1- and 2-year overall survival rates were 65.5% (52.9–78.0%) and 39.4% (25.3–53.5%), respectively. Disease progression occurred in 38 patients, and the 1- and 2-year progression-free survival rates were 36.2% (23.1–49.4%) and 24.9% (12.7–37.2%), respectively. Local recurrence was observed in 13 patients, and the 1- and 2-year local control rates were 79.1% (66.8–91.3%) and 64.1% (47.5–80.7%), respectively. Grade ≥3 lung toxicity was seen in six patients, esophageal toxicity occurred at grade ⩽2, and there was no cardiac toxicity.Conclusion:The prognosis of patients with unresectable stage III NSCLC is poor without chemotherapy. Our data suggest that high-dose PBT is beneficial and tolerable for these patients

Brachytherapy in Japan

This study aimed to assess the current state of brachytherapy (BT) resources, practices and resident education in Japan. A nationwide survey was undertaken encompassing 177 establishments facilitating BT in 2022. Questionnaires were disseminated to each BT center, and feedback through online channels or postal correspondence was obtained. The questionnaire response rate was 90% (159/177), and every prefecture had a response in at least one center. The number of centers in each prefecture ranged from 0.6 to 3.6 (median: 1.3) per million population. The annual number of patients in each center ranged from 0 to 272 (median: 31). While most prefectures provided intracavitary (IC) BT for gynecological cancers and interstitial (IS) BT for prostate cancer, only one-third of the prefectures provided IS BT for cancer sites other than the prostate. The institutional image-guided BT implementation rate was 71%. IC and IS BT was performed for 15.4% of IC BT cases of gynecological cancer. Only 47% of the BT training centers answered that they could provide adequate training in BT for residents. The most common reason for this finding was the insufficient number of patients in each center. The results show that, although BT has achieved uniformity in terms of facility penetration, new technologies are not yet widespread enough. Furthermore, IS BT, which requires advanced skills, is limited to a few BT centers, and considerable number of BT training centers do not have sufficient caseloads to provide the necessary experience for their residents