Journal of Radiation Research最新文献

The role of the Certified Nurse in Radiation Oncology nursing (CN-RO) has expanded to include support for ensuring treatment reproducibility and minimizing medical radiation exposure through radiation protection measures. In hypofractionated radiotherapy for prostate cancer, in which consistent pretreatment bladder volume is more critical than in conventional fractionation, whether CN-RO intervention contributes to bladder volume reproducibility and reduction of cone-beam computed tomography (CBCT) frequency, lowering radiation exposure, was investigated. Sixty prostate cancer patients undergoing hypofractionated radiotherapy (51.6 Gy in 12 fractions) were retrospectively analyzed. Twenty patients received CN-RO intervention (Current Intervention (CI) group), which involved dehydration risk assessment and bladder volume guidance using a handheld bladder ultrasound scanner from the first session. Forty patients received no such intervention (Previous Intervention (PI) group). Bladder volume reproducibility, calculated as treatment bladder volume divided by planning bladder volume, and the number of CBCT scans were compared between the groups. The target was to achieve ≥70% reproducibility and to initiate treatment with the first CBCT scan in all sessions. There was no significant difference in bladder volume at treatment planning between the groups (P = 0.851). Mean bladder volume reproducibility was significantly higher in the CI group (96.5 ± 12.0%) than in the PI group (86.9 ± 14.2%, P = 0.022). Treatment was initiated after the first CBCT scan in 95.4% of sessions in the CI group (229/240), compared with 80.0% in the PI group (384/480, P < 0.001). These results suggest that CN-RO intervention enhances bladder volume reproducibility and contributes to reduced radiation exposure through fewer CBCT scans.

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.

Non-small cell lung cancer (NSCLC) constitutes 80-85% of lung cancers, with advanced cases showing a 20-30% 5-year survival rate. Radiation resistance limits radiotherapy efficacy, and the function of NOP58 in this process is unknown. This study investigated the mechanisms of NOP58 in NSCLC radioresistance. A radiation-resistant NSCLC cell line (H1299R) was established. Bioinformatic analysis of the Cancer Genome Atlas Program data revealed that high NOP58 expression correlates with poor patient prognosis. The expression levels of NOP58 and DDX18 expression were quantified via quantitative real-time polymerase chain reaction and Western blot. Radiosensitivity of H1299R cells and parental H1299 cells was assessed under irradiation (0, 2, 4, 6 and 8 Gy). Cell viability was assessed using cell counting kit-8 and colony formation assays. Apoptosis was detected by flow cytometry with Annexin V/PI staining. DNA damage was analyzed via γ-H2AX immunofluorescence and comet assays. NOP58 knockdown and DDX18 overexpression were performed for rescue experiments, and protein interaction was validated by pull-down assays. NOP58 and DDX18 were significantly upregulated in H1299R cells. H1299R cells exhibited higher cell viability, stronger colony-forming capacity, reduced apoptosis and less DNA damage under irradiation treatment. The depletion of NOP58 in H1299 and H1299R cells exacerbated radiation-induced DNA damage, reduced cell viability and promoted apoptosis, reversing radioresistance. Direct interaction between NOP58 and DDX18 was confirmed by pull-down assay. DDX18 overexpression reversed the radiosensitizing effects of NOP58 knockdown, including attenuated DNA damage and restored cell survival. Overexpression NOP58 converted radiosensitive cells to a resistant phenotype. NOP58 promotes NSCLC radioresistance by interacting with DDX18, regulating its expression and thereby suppressing radiation-induced DNA damage. The NOP58-DDX18 axis could be a promising therapeutic target for improving radiotherapy efficacy in NSCLC.

Proton beam therapy (PBT) provides sharper dose gradients than conventional photon radiotherapy, potentially reducing radiation exposure to normal tissues. However, acute genitourinary adverse events (GU AEs) remain a clinical concern. This study aimed to evaluate the incidence and predictors of grade ≥ 2 acute GU AEs in patients with localized prostate cancer treated with real-time image-gated, spot-scanning PBT (RGPT). We analyzed the prospective study data of 326 patients who received RGPT at a dose of 63 Gy (relative biological effectiveness [RBE]) in 21 fractions between 2019 and 2021. Acute GU AEs were graded according to the Common Terminology Criteria for Adverse Events (version 5.0). Multivariable logistic regression was used to analyze potential predictive factors, including baseline International Prostate Symptom Score (IPSS), age, comorbidities, hydrogel spacer placement, use of anticoagulants or urinary symptom medications, clinical stage, National Comprehensive Cancer Network (NCCN) risk classification, prostate volume, and dose-volume histogram parameters. Grade 2 acute GU AEs occurred in 127 patients (39.0%), whereas no grade ≥ 3 events were observed. Moderate (odds ratio [OR] = 1.71; 95% confidence interval [CI]: 1.03-2.82) and severe (OR = 3.75; 95% CI: 1.49-9.46) baseline IPSS, as well as age ≥ 75 years (OR = 1.80; 95% CI: 1.10-2.95), were significant independent predictors of grade ≥ 2 GU AEs. No dose-volume histogram parameters were significantly associated with grade ≥ 2 GU AEs. Baseline urinary symptoms and older age were independent predictors of grade ≥ 2 GU AEs, emphasizing the importance of pretreatment evaluation in optimizing patient selection and management.

This study evaluated the cost-effectiveness of hypofractionated intensity-modulated radiation therapy delivered in 20 fractions (IMRT-20) compared with robot-assisted radical prostatectomy (RARP) for patients with localized low-risk prostate cancer in Japan. A state-transition Markov model was developed from the Japanese healthcare system, using Japanese-specific cost data. Clinical probabilities, adverse event rates and health utility values were primarily derived from international sources, including the ProtecT trial, with extensive sensitivity and scenario analyses to address parameter uncertainty. The base-case analysis compared IMRT-20 and RARP. Scenario analyses included conventional fractionated IMRT (IMRT-38) versus RARP, as well as IMRT-20 versus RARP excluding the utility decrement associated with sexual dysfunction to explore preference-sensitive outcomes. Model outputs included quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefit (INMB). In the base-case analysis, IMRT-20 yielded a modest QALY gain (0.1164) at slightly higher costs compared with RARP, resulting in an ICER of JPY 143 685 per QALY, well below the Japanese willingness-to-pay threshold of JPY 5 000 000 per QALY. Probabilistic sensitivity analysis showed that IMRT-20 was cost effective in 78.1% of simulations. IMRT-38 was less cost effective because of longer treatment duration and higher resource utilization (ICER JPY 3 317 380 per QALY), although it remained below the threshold. When the disutility of sexual dysfunction was excluded, IMRT-20 was dominated by RARP; however, INMB analysis indicated that IMRT-20 became economically favorable when the disutility exceeded 20%. Overall, IMRT-20 represents a clinically and economically efficient definitive treatment strategy for localized low-risk prostate cancer in Japan, supporting value-based cancer care.

Dynamic tumor tracking (DTT) is an effective respiratory motion management strategy for thoracic and abdominal tumors and enables treatment delivery under free breathing using gimbal-mounted linac, without requiring breath-holding. To date, however, clinical implementations have used three-dimensional conformal radiotherapy (3D-CRT) or fixed-field intensity-modulated radiotherapy (IMRT), and integration with volumetric modulated arc therapy (VMAT) has been anticipated to shorten treatment time while improving dose distribution. This short communication reports the first clinical implementation of stereotactic body radiotherapy with DTT-VMAT using a novel gimbal-mounted linac. Planned treatment using DTT-VMAT for liver tumor over five treatment days was delivered successfully, with a mean treatment time of 23.2 min (range, 12-33 min), shorter than previously reported gimbal-based DTT with 3D-CRT or fixed-field IMRT. The average 3D tracking error was 2.4 ± 1.8 mm overall, comprising 0.3 ± 1.0 mm laterally, -1.5 ± 2.2 mm longitudinally and - 0.1 ± 1.0 mm vertically, maintaining tracking performance comparable to earlier systems. No updates to the four-dimensional model were required during beam delivery. This introduction of novel gimbaled-based DTT-VMAT approach is advantageous among available respiratory motion management techniques, as it shortens treatment time, mitigates baseline drift and improves patient compliance.

We investigated the feasibility of a biological dosimetry method using human hair follicle dermal papilla cells (HFDPCs). Cultured HFDPCs were X-irradiated at doses of 50-20 000 mGy, and 53BP1 foci were analyzed up to 96 h post-irradiation to assess DNA double-strand break repair kinetics and dose-response relationships. Up to 5 h post-irradiation, 53BP1 foci increased in a significant dose-dependent manner from 50 to 1000 mGy. By 24 h, the foci count at 50 mGy returned to background levels, whereas dose dependence persisted at higher doses. Notably, analysis of the focus size revealed that the proportion of large foci (diameter ≥ 1 μm) significantly increased at doses ≥ 3000 mGy at 24 h. At 96 h post-irradiation, while total focus counts showed limited discrimination, large-foci assessment maintained significant sensitivity for doses as low as 500 mGy). These findings demonstrate that 53BP1 focus counting in HFDPCs allows for dose estimation from 50 mGy at 5 h, while focus size analysis enhances the accuracy for threshold-based estimation of doses ≥ 500 mGy up to 96 h. This study provides foundational data demonstrating the potential of HFDPCs for biological dosimetry and medical triage, warranting further validation using intact hair samples.

Daily attendance requirements for radiotherapy (RT) make geographic accessibility a critical determinant of treatment adherence and completion. Although facility surveys indicate that advanced modalities such as intensity-modulated radiotherapy (IMRT) and brachytherapy are concentrated in urban centers, precise nationwide quantification of the resulting patient travel burden remains lacking. This study provides the first nationwide, modality-stratified assessment of geographic access to RT in Japan. Using the Open Source Routing Machine and a high-resolution dataset of 176 964 household-weighted 1-km mesh centroids, we calculated driving times to the nearest external-beam radiotherapy (EBRT), IMRT and brachytherapy facilities. Beyond standard distribution metrics, we generated high-resolution 'penalty maps' to quantify the incremental time tax imposed by advanced modality requirements. Although EBRT access was uniformly short nationwide, with a median travel time of 6.48 min, this increased to 8.26 min for IMRT and 14.06 min for brachytherapy. Crucially, the proportion of the population facing poor access (≥120 min) doubled from 0.24% for EBRT to 0.48% for brachytherapy. The spatial analysis identified specific 'newly poor-access' areas-regions that are accessible for EBRT but become remote when advanced care is needed-forming coherent geographic clusters in mountainous and island zones. These findings demonstrate that modality requirements introduce meaningful inequities despite strong national EBRT infrastructure. These indicators provide a vital evidence base for spatially optimizing resources to mitigate travel burdens for Japan's aging, mobility-limited population.

Competitive transplantation of cells expressing distinct fluorescent proteins is an attractive method for assessing cell competition and tumor clonality, albeit its use has been limited to mouse models. Rat mammary cancer is an alternative model to mice due to its similarity to human breast cancer. This study aims to implement competitive transplantation in the context of radiation biology of the rat mammary gland and to provide a detailed protocol on key techniques. Dissociated mammary cells were obtained from wild-type and transgenic rats expressing either green (EGFP) or red (Discosoma sp. red fluorescent protein [DsRed]) fluorescent protein. The cells were exposed to γ rays or left untreated, mixed at a specific ratio and then transplanted into the cleared fat pads of wild-type or double transgenic rats. We evaluated the expression of fluorescent proteins in epithelial outgrowths using confocal imaging of cleared tissues or on histological sections. Transplanting transgenic cells into wild-type recipients induced inflammation and rejection of the donor cells. Conversely, transplanting into double transgenics resulted in successful repopulation and observation of the fluorescent markers. A competitive assay between irradiated EGFP-expressing cells and unirradiated DsRed-expressing cells revealed that radiation exposure (4 Gy) did not affect repopulating ability, despite the theoretical sensitivity of the assay, suggesting the absence of strong competition between these cells. Analysis of tumors revealed the polyclonal nature of adenomas that developed in recipients exposed to radiation or 1-methyl-1-nitrosourea. Thus, this study developed a method to track cells in the rat mammary gland that is useful in radiation biology.