Katsumasa Nakamura

The lung is among the most radiosensitive organs and a principal dose-limiting organ in thoracic radiotherapy, yet the acute metabolic consequences of irradiation at the lipidomic level remain poorly characterized. We constructed a time-resolved lipidomic atlas of the murine lung response to high-dose irradiation. Male C57BL/6 J mice received a single 10 Gy whole-body X-ray dose, and lungs were collected at 5 minutes, 1 hour, 4 hours, and 24 hours post-exposure (n = 5 per group) and analyzed by untargeted liquid chromatography–tandem mass spectrometry. Radiation triggered rapid and coordinated lipid remodeling. Principal component analysis revealed a structured temporal trajectory, and oxidized lipid species increased significantly by 24 hours. Pulmonary surfactant lipids, including dipalmitoylphosphatidylcholine and phosphatidylglycerol, underwent early and progressive oxidation. Membrane signaling lipids shifted in a manner consistent with a transient pro-survival bias, with ceramide depletion, sphingomyelin accumulation, and phosphatidylserine oxidation. Mitochondrial lipids displayed a coordinated triad of early cardiolipin oxidation, progressive coenzyme Q depletion, and sustained phosphatidylethanolamine accumulation. Lysobisphosphatidic acid accumulated steadily, consistent with endolysosomal activation, while storage triglycerides and diglycerides were rapidly mobilized and free fatty acids accumulated at later time points. Class-level changes were temporally ordered and compartmentally organized, indicating that the acute lipid response is not confined to oxidative damage. The lipid classes involved overlap with those implicated in ferroptosis, mitophagy, lipophagy, and surfactant biology, although these processes were not assessed directly here. This atlas is offered as a descriptive resource for mechanistic study of radiation-induced lung injury.

This study aimed to quantitatively evaluate and compare the couch motion, particularly the sag, of a treatment planning CT system and a Radixact treatment system using a wide-area three-dimensional coordinate measuring machine. We assessed the couch movement of a treatment planning CT and a Radixact X9 system. A total load of 60 kg was applied to each couch. The three-dimensional positions of three points on each couch were measured as the couch moved in 200 mm increments up to a distance of 1,200 mm. We evaluated vertical displacement (sag), longitudinal movement accuracy, and lateral deviation using a wide-area three-dimensional coordinate measuring machine. A significant couch sag, reaching a maximum of 4.12 mm in the Z-axis, was observed on the imaging plane of the treatment planning CT. In contrast, the Radixact system, equipped with a couch catcher, showed a maximum sag of only 0.13 mm in the treatment plane. Both couches demonstrated extremely high accuracy in longitudinal movement and straightness, with minimal lateral deviation. The Radixact's couch catcher effectively suppresses couch sag during treatment. However, the substantial discrepancy in sag between the treatment planning CT and the Radixact system poses a risk of compromising treatment accuracy by creating a gap between the planned and delivered positions. A three-dimensional coordinate measuring machine enables highly accurate measurement of couch motion, revealing discrepancies that should be accounted for during the treatment planning process.

Background/Objectives: Transthoracic echocardiography (TTE) is a non-invasive tool for real-time assessment of cardiac motion and blood flow. It is widely used in emergency and bedside settings as a Focus Cardiac Ultrasound (FoCUS) device. However, standardized training methods and adequate educational environments are limited. Methods: A TTE image assessment artificial intelligence (AI) system was developed in this study, focusing on probe positioning and image quality for non-supervised TTE practice. Results: The view classification model achieved a high F1-score of 0.956. The position evaluation model achieved F1-scores of 0.678, 0.864, and 0.831 for the parasternal long-axis, parasternal short-axis, and apical four-chamber views, respectively. The quality evaluation model achieved F1-scores of 0.674, 0.845, and 0.746. Combining the position and quality models improved the F1-score for the parasternal long-axis view to 0.714, showing the benefit of integrating views with lower baseline performance. Conclusions: This study presents a novel AI-based educational system that assesses probe position and image quality in TTE. The model was developed using a custom dataset of healthy young adults that reflects beginner-level training scenarios, including many suboptimal images similar to those commonly acquired by novices. The proposed framework, which integrates position and quality models, lays the groundwork for future AI-assisted ultrasound training, particularly in unsupervised or resource-limited settings.

Radiodynamic therapy enables treatment of deep-seated tumors but typically requires scintillator nanoparticles with associated toxicity concerns. While porphyrin photosensitizers (PS) have been shown to enhance reactive oxygen species (ROS) generation under X-ray irradiation without scintillators, the molecular features governing this effect remain unclear. Here, we systematically examined structure–activity relationships of nine porphyrin derivatives to elucidate the design principles for scintillator-free radiosensitizers. Molecular charge critically influenced ROS modulation: anionic tetrakis (4-carboxyphenyl) porphyrin showed the highest efficacy with approximately 7-fold enhancement over X-ray alone, whereas cationic tetra (N-methyl-4-pyridyl) porphyrin suppressed ROS below control levels. Notably, heavy-atom coordination yielded structure-dependent effects rather than uniform enhancement, distinguishing this process from conventional photodynamic therapy. Using complementary ROS probes, we found that X-ray-mediated ROS generation produces predominantly superoxide and hydrogen peroxide rather than singlet oxygen, suggesting electron transfer rather than energy transfer as the operative pathway. Dose–response analysis demonstrated that ROS generation scales linearly with radiation dose, indicating no saturation within the therapeutic window. Validation with clinically relevant PS showed that Visudyne and protoporphyrin IX—both bearing anionic carboxylate groups—were active. However, the inactivity of anionic but rigid rose bengal suggests that electrostatic properties alone are insufficient. These findings suggest that along with molecular charge, conformational flexibility—potentially facilitating internal conversion from high-energy excited states—represents a key design parameter for scintillator-free radiosensitizers. This approach offers a simplified, biocompatible formulation strategy for deep-tissue cancer therapy without relying on heavy-metal nanoscintillators.

During the coronavirus disease 2019 (COVID-19) pandemic, a short-term decline in radiotherapy use was reported. In this study, we investigated long-term changes in the use of radiotherapy and hypofractionated radiotherapy before and after the COVID-19 pandemic period in Japan and assessed whether the pandemic influenced the adoption of hypofractionation. We obtained data for analysis from the National Database Open Data for fiscal years (FYs) 2014 to 2023. For the 5 years from FY2019 to FY2023, with detailed monthly data available, we used interrupted time series (ITS) analysis to examine changes in the level and slope of claims at the boundaries of the baseline, pandemic and post-pandemic periods. During the 10-year study period, the number of radiotherapy claims increased by an average of 1.6% per year. In FY2020, the peak of the COVID-19 pandemic, the number of radiotherapy claims decreased by 2.0% compared to the previous year. The number of claims for extra fees for hypofractionated radiotherapy for breast and prostate cancer showed a steady increase, except for a temporary decline around the April 2022 policy change in payment requirements for prostate cancer. In the ITS analysis, there were no significant changes in the level and slope of claims for radiotherapy and extra fees for hypofractionated radiotherapy at the onset of the pandemic. In conclusion, the impact of the COVID-19 pandemic on the utilization of radiotherapy in Japan was minimal, and the use of hypofractionated radiotherapy showed a steady increase throughout this period.

Helical tomotherapy-based total body irradiation (TBI) traditionally employs megavoltage computed tomography (MVCT) for image-guided setup; however, its 390 mm field of view (FOV) and long acquisition times constrain workflow efficiency and whole-body alignment. This study evaluated whether a newly implemented whole-body fan-beam kilovoltage CT (kVCT; 500 mm FOV) can streamline this process. In a retrospective study involving 14 patients treated with a Radixact X9 system (September 2021–September 2023), we timed the patient setup, imaging, registration, re-setup, and beam delivery for each upper-body (UB) and lower-body (LB) segment. Residual setup errors were measured along the lateral, longitudinal, and vertical axes. The kVCT shortened the initial setup cycle (setup + imaging + registration) from 25.4 ± 4.6 to 15.9 ± 3.3 min for UB and from 14.5 ± 3.8 to 9.4 ± 2.4 min for LB (P < 0.001 for both). The total fraction time, including delivery time, decreased from 71.8 ± 7.5 to 56.7 ± 5.3 min. When residual errors exceeded 5 mm, the additional time required for a second cycle was nearly halved with kVCT (7.3 vs. 14.3 min for UB; 4.8 vs. 8.2 min for LB). The kVCT maintained mean absolute residual errors below 2 mm in all axes, and every 95th-percentile value remained within the 5 mm tolerance recommended for tomotherapy-based TBI. These time savings are expected to reduce intrafraction motion and staff workload. Overall, whole-body kVCT enables faster, comprehensive image guidance while preserving accuracy, thereby streamlining tomotherapy-based TBI and reducing the burden on patients and clinical staff.

Objectives: This multicenter study aimed to clarify the recurrence patterns; treatment outcomes; and prognostic factors of thymic carcinoma, a rare cancer. Methods: We analyzed 101 patients with thymic carcinoma who underwent multidisciplinary treatment, including radiotherapy. The median age was 62 years, with 27 patients in stage I–II; 44 in stage III; and 30 in stage IV by the TNM classification. Seventy-two patients underwent surgery with radiotherapy; and 29 patients underwent definitive radiotherapy. Image-guided radiotherapy (IGRT) and elective nodal irradiation (ENI) were used for 35 and 23 patients, respectively. Local recurrence-free survival (LRFS); progression-free survival (PFS); and overall survival (OS) were calculated, and univariate and multivariate analyses were performed. Results: With a median follow-up of 68 months, we observed 17 local recurrences; 27 regional recurrences; and 35 distant metastases. The 5-year LRFS; PFS; and OS were 82%, 41%, and 76%, respectively. Multivariate analysis revealed that stage was the only factor associated with LRFS; PFS; and OS (p = 0.040; p < 0.0001; and p = 0.048, respectively), while treatment modality was associated with only LRFS (p = 0.015). IGRT and ENI were also associated with LRFS (p = 0.002 and 0.013, respectively). PFS and OS of stage IV patients were comparable between the surgery with radiotherapy and definitive radiotherapy groups (p = 0.99 and 0.98, respectively). Conclusions: Our results suggest the importance of stage-specific treatment strategies rather than resectability, especially for stage IV patients. These results should be validated in a prospective study. Our results also suggest that radiotherapy methods influence recurrence

Background: One method for noninvasive and simple urinary microalbumin testing is urine test strips. However, when visually assessing urine test strips, accurate assessment may be difficult due to environmental influences—such as lighting color and intensity—and the physical and psychological influences of the assessor. These complicate the formation of an objective assessment. Objectives: This study developed an “automated urine test strip colorimetric program” (hereinafter referred to as “this program”) to objectively assess urine test strips. Using this program may allow urine tests to be conducted at home. In this study, urine samples from hospitalized or outpatient patients were randomly obtained, and the reliability of this program was verified by comparing the agreement rate between this program and an automatic urine analyzer (US-3500 [Eiken Chemical Co, Ltd] and LABOSPECT 006 [Hitachi High-Tech Co, Ltd]). Furthermore, the sensitivity and specificity of the urine albumin test were investigated, and its applicability to screening for microalbuminuria was verified. Methods: A urine test strip was placed in a photography box with constant light intensity and color temperature conditions. The image taken with a smartphone camera on top of the photography box was judged by this program. This program used Accelerated KAZE to perform image-matching processing to reduce the effect of misalignment during photography. It also calculated and judged the item with the smallest color difference between the color chart and the urine test strip using the CIEDE2000 color difference formula. The agreement rate of the results of this program was investigated using the results of an automatic urine analyzer as the gold standard. Results: Compared with the judgments of an automatic urine analyzer, the average agreement rate for 12 items (protein, glucose, urobilinogen, bilirubin, ketone bodies, specific gravity, occult blood, pH, white blood cells, nitrite, creatinine, and albumin) was 78.6%. Furthermore, the average agreement rate of the 12 items within ±1 rank was 95.4%. The results showed a sensitivity of 100% and a specificity of 58.6% in determining albumin in urine, which is important for determining the stage of diabetic nephropathy. Finally, the area under the curve (0.907) derived from the receiver operating characteristic curve was satisfactory. Conclusions: The program developed by the authors can determine urine test strips without requiring calibration in a certain shooting environment. If this program can be used at home to perform urinary microalbumin tests, the early detection and treatment of diabetic nephropathy may prevent the condition from becoming severe.

Background The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. Methods Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4–8 months was mandatory for patients with intermediate or high-risk prostate cancer. Results From 20 institutions, 134 patients enrolled. The median follow-up was 5.16 years (range, 1.43–6.47 years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5 years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3–16.2%, p = 0.0958). Conclusion The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

Background Although moderate hypofractionated radiotherapy were one of standard regimens for localized prostate cancer, the efficacy of moderated hypofractionated regimens has not been well validated in Asian countries. The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. Methods Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included in this trial. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8 months was mandatory for patients with intermediate or high-risk prostate cancer. Results The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal and genitourinary late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Conclusion The safety and efficacy of moderately hypofractionated IMRT was confirmed in this trial among Japanese patients with prostate cancer.