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The dose rate of atomic bomb (A-bomb) radiation to the survivors has still remained unclear, although the dose–response data of A-bomb cancers has been taken as a standard in estimating the cancer risk of radiation and the dose and dose-rate effectiveness factor (DDREF). Since the applicability of the currently used DDREF of 2 derived from A-bomb data is limited in a narrow dose-rate range, 0.25-75 Gy/min as estimated from analysis of DS86 dosimetry data in the present study, a non-tumor dose (Dnt) was applied in an attempt to gain a more universal dose-rate effectiveness factor (DREF), where Dnt is an empirical parameter defined as the highest dose at which no statistically significant tumor increase is observed above the control level and its magnitude depends on the dose rate. The new DREF values were expressed as a function of the dose rate at four exposure categories, i.e. partial body low LET, whole body low linear energy transfer (LET), partial body high LET and whole body high LET and provided a value of 14 for environmental level radiation at a dose rate of 10−9 Gy/min for whole body low LET.

We retrospectively assessed whether magnetic resonance imaging (MRI) radiomics combined with clinical parameters can improve the predictability of out-of-field recurrence (OFR) of cervical cancer after chemoradiotherapy. The data set was collected from 204 patients with stage IIB (FIGO: International Federation of Gynecology and Obstetrics 2008) cervical cancer who underwent chemoradiotherapy at 14 Japanese institutes. Of these, 180 patients were finally included for analysis. OFR-free survival was calculated using the Kaplan–Meier method, and the statistical significance of clinicopathological parameters for the OFR-free survival was evaluated using the log-rank test and Cox proportional-hazards model. Prediction of OFR from the analysis of diffusion-weighted images (DWI) and T2-weighted images of pretreatment MRI was done using the least absolute shrinkage and selection operator (LASSO) model for engineering image feature extraction. The accuracy of prediction was evaluated by 5-fold cross-validation of the receiver operating characteristic (ROC) analysis. Para-aortic lymph node metastasis (p = 0.003) was a significant prognostic factor in univariate and multivariate analyses. ROC analysis showed an area under the curve (AUC) of 0.709 in predicting OFR using the pretreatment status of para-aortic lymph node metastasis, 0.667 using the LASSO model for DWIs and 0.602 using T2 weighted images. The AUC improved to 0.734 upon combining the pretreatment status of para-aortic lymph node metastasis with that from the LASSO model for DWIs. Combining MRI radiomics with clinical parameters improved the accuracy of predicting OFR after chemoradiotherapy for locally advanced cervical cancer.

Mental disorders are common health concerns and contribute to a heavy global burden on our modern society. It is challenging to identify and treat them timely. Neuroimaging evidence suggests the incidence of various psychiatric and behavioral disorders is closely related to the atypical development of brain structure and function. The identification and understanding of atypical brain development provide chances for clinicians to detect mental disorders earlier, perhaps even prior to onset, and treat them more precisely. An invaluable and necessary method in identifying and monitoring atypical brain development are growth charts of typically developing individuals in the population. The brain growth charts can offer a series of standard references on typical neurodevelopment, representing an important resource for the scientific and medical communities. In the present paper, we review the relationship between mental disorders and atypical brain development from a perspective of normative brain development by surveying the recent progress in the development of brain growth charts, including four aspects on growth chart utility: 1) cohorts, 2) measures, 3) mechanisms, and 4) clinical translations. In doing so, we seek to clarify the challenges and opportunities in charting brain growth, and to promote the application of brain growth charts in clinical practice.

The present study aimed to reduce the parotid gland dose in the hippocampus avoidance with whole-brain radiotherapy (HA-WBRT) using the helical tomotherapy (HT). Ten patients who had previously undergone WBRT were randomly selected and enrolled in this study. During the treatment planning, two different techniques to the jaw were applied for each patient, namely, 1.0 cm fixed jaw and 2.5 cm dynamic jaw. To efficiently reduce the dose in the bilateral parotid glands, directional block (DB) mode was set. The DB is a function of a treatment planning system for the dose reduction in organs at risk. The standard HA-WBRT plan which did not reduce the parotid gland dose was also designed to compare the plan quality. Compared with the standard HA-WBRT plan, the parotid gland dose could be reduced by approximately 70% without extending the delivery time by adding the parotid gland on the DB mode to the dose constraint. In addition, the differences in dosimetric parameters observed between the plans employing the 1.0 cm fixed jaw and 2.5 cm dynamic jaw were almost negligible. Moreover, delivery time in the 2.5 cm dynamic jaw could be greatly reduced by 60% compared with that in the 1.0 cm fixed jaw.

The irradiated volume of intestines is associated with gastrointestinal toxicity in preoperative chemoradiotherapy for rectal cancer. The current trial prospectively explored how much of the irradiated volume of intestines was reduced by intensity-modulated radiotherapy (IMRT) compared with 3-dimensional conformal radiotherapy (3DCRT) and whether IMRT might alleviate the acute gastrointestinal toxicity in this population. The treatment protocol encompassed preoperative chemoradiotherapy using IMRT plus surgery for patients with clinical T3–4, N0–2 low rectal cancer. IMRT delivered 45 Gy per 25 fractions for gross tumors, mesorectal and lateral lymph nodal regions, and tried to reduce the volume of intestines receiving 15 Gy (V15 Gy)

According to guidelines, carbon-ion beam therapy is considered to carry a high safety risk for patients with cardiac implantable electronic devices (CIEDs), although the actual impacts remain unclear. In this study, we investigated the safety of carbon-ion beam therapy in patients with CIEDs. Patients with CIEDs who underwent carbon-ion therapy at Gunma University Heavy Ion Medical Center between June 2010 and December 2019 were identified and investigated for abnormalities in the operation of their CIEDs, such as oversensing and resetting during irradiation, and abnormalities in operation after treatment. In addition, the risk of irradiation from carbon-ion beam therapy was evaluated by model simulations. Twenty patients (22 sites) with CIEDs were identified, 19 with pacemakers and one with an implantable cardioverter-defibrillator (ICD). Treatments were completed without any problems, except for one case in which the treatment was discontinued because of worsening of the primary disease. Monte Carlo simulation indicated that the carbon beam irradiation produced neutrons at a constant and high level in the irradiation field. Nevertheless, with the distances between the CIEDs and the irradiation fields in the analyzed cases, the quantity of neutrons at the CIEDs was lower than that within the irradiation. Although carbon-ion beam therapy can be safely administered to patients with CIEDs, it is advisable to perform the therapy with sufficient preparation and backup devices because of the risks involved.

Although the health effects of exposure to low-dose ionizing radiation have been the focus of many studies, the affected biological functions and underlying regulatory mechanisms are not well-understood. In particular, the influence of radiation exposure at doses of less than 200 mGy on the regulation of genes and pathways remains unclear. To investigate the molecular alterations induced by varying doses of low-dose radiation (LDR), transcriptomic analysis was conducted based on ribonucleic acid (RNA) sequencing following exposure to 50 and 150 mGy doses. Human peripheral blood was collected, and the samples were divided into three groups, including two treatments and one control (no radiation). A total of 876 (318 upregulated and 558 downregulated) and 486 (202 upregulated and 284 downregulated) differentially expressed genes (DEGs) were identified after exposure to 50 mGy and 150 mGy, respectively. Most upregulated genes in both the 50 mGy and 150 mGy groups were associated with ‘antigen processing and presentation,’ which appeared to be the major targets affected by LDR exposure. Several interacting genes, including HLA-DQA1, HLA-DQA2, HLA-DQB2, HLA-DRB1, and HLA-DRB5 were mapped to ‘antigen processing and presentation,’ ‘immune system-related diseases’ and the ‘cytokine-mediated signaling pathway,’ suggesting that these genes might drive the downstream transmission of these signal transduction pathways. Our results suggest that exposure to LDR may elicit changes in key genes and associated pathways, probably helping further explore the biological processes and molecular mechanism responsible for low-dose occupational or environmental exposures in humans.

The purpose of this study is to investigate the frequency of education, knowledge of radiation and workplace anxiety of Fukushima Daiichi Nuclear Power Plant (FDNPP) workers and to analyze what type of words are used for anxiety with a text mining method. An original questionnaire survey was given to FDNPP workers, and a text mining method was used to extract information from free-entry fields. The questionnaires were collected from 1135 workers (response rate: 70.8%). It was found that when workers receive education on radiation, the increased knowledge helps to reduce their anxiety. Among the 1135 workers, 92 of 127 completed the free-entry field with valid entries. Seventy-one words were extracted by the text mining method. The words used differed depending on the degree of anxiety. The text mining method revealed information about the presence or absence of radiation anxiety and the subjects’ working environment and background.

This study aimed to quantitatively clarify the baseline drift for each respiratory cycle in two respiratory-gating methods using the intra-beam respiratory motion data of lung cancer patients. The residual motion and dose distribution were calculated based on intra-beam respiratory motion data with the baseline drift. To quantify the baseline drift \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\Delta$\end{document} during irradiation, it was defined as the inclination between the detected expiration point and the expiration point in the next cycle in the anterior–posterior (AP), cranial–caudal (CC) and left–right (LR) directions obtained using an in-house programme. The baseline drift value reached up to 0.74 mm/s in the CC direction as per the respiratory motion data of 10 patients. The homogeneity index (HI) of the phase-gating method tended to increase because the target was irradiated even when the amplitude position of the target differed from period to period. In contrast, the amplitude-gating method enabled irradiation considering the amplitude position of the target because the gating window was set considering the amplitude position of the respiratory motion. The respiratory-gating methods and respiratory phase in respiratory-gating lung stereotactic body radiation therapy (SBRT) must be determined based on the respiratory motion of the patients.

Oral administration of a water-soluble iodine contrast agent (gastrografin) was reported to assist in the appropriate contouring of the small intestine on computed tomography (CT)-based radiotherapy (RT) planning. The efficacy and optimal dose of gastrografin in CT-based image-guided brachytherapy (IGBT) for cervical cancer remain unknown. This study aimed to investigate the efficacy of pretreatment oral administration of gastrografin at a small dose of 50 ml in CT-based IGBT for cervical cancer. A total of 422 sessions in 137 patients who underwent CT-based IGBT with 50 ml of oral gastrografin (concentration, 3% or 4%) were analyzed. Preparation of gastrografin was judged as effective when the small intestine was contrast-enhanced at the area where the small intestine was in contact with the uterus/adnexa. About 287 out of 422 sessions (68%) were judged as effective with gastrografin preparation. The 135 ineffective sessions were considered as follows: (i) the contrast enhancement of the small intestine was not confirmed (n = 36), (ii) the small intestine was not in contact with the uterus/adnexa despite the confirmation of the contrast enhancement of the small intestine (n = 34), and (iii) gastrografin was absent in the small intestine at the area in contact with the uterus/adnexa, even when gastrografin was observed in the small intestine at the area not in contact with the uterus/adnexa (n = 65). In conclusion, pretreatment oral administration of a small dose gastrografin achieved moderate efficacy for accurate contouring of the small intestine close to the uterus/adnexa in CT-based IGBT for cervical cancer.

We hypothesize that there is a risk of ipsilateral breast tumor recurrence (IBTR) in surgical margin-free invasive ductal carcinoma (IDC) in the presence of ductal carcinoma in situ (DCIS) component affecting surgical margins in early stage. From 1990 to 2014, 343 patients with IDC in which the DCIS component constitute have received radiotherapy (RT) following breast-conserving surgery (BCS). All patients received whole breast irradiation with a prescribed dose of 50 Gy in 20 fractions (four times a week). This one-arm cohort with boost RT (253 patients) was compared for IBTR with a non-cohort group receiving no boost RT because of freedom from positive margins (90 patients). Median observation months were 98 (boost group) vs 119 (no boost group), respectively. The 15-year local recurrence-free survival (LRFS) rates were 98.5% and 85.6% in the boost and no boost groups, respectively (Cox proportional hazards model univariate analysis; p = 0.013, HR 0.13). Similarly, for other background factors, there was a significant difference in the LRFS between age groups. The 15-year LRFS rate was 91.8% in patients aged 45 years or younger and 94.6% in patients older than 46 years (p = 0.031, HR 0.21), respectively. Only these two factors were independently significant in Cox proportional hazards model multivariate analysis. IBTR risk in margin-free IDC with DCIS component was independently decreased by boost RT in the cohort setting. Tumor size, extensive intraductal component (EIC), boost dose, the presence of lymph node (LN) metastasis and hormonal therapy were not IBTR risk factors in this study.

Ionizing radiation exposure affects the redox state in vivo. Recently, whole-blood antioxidant capacity (WBAC) has been reported to decrease in a dose-dependent manner after acute total body irradiation (TBI). However, changes in WBAC after localized and chronic irradiations have not been reported. This study analyzed changes to WBAC in mice after either localized irradiation (irradiation of the left hind leg only) or chronic TBI using the i-STrap method. Leg-localized irradiation exerted limited effects on WBAC, while WBAC decreased in a dose rate-dependent manner after TBI. Further, the WBAC reached the minimum value in a shorter period at a smaller dose rate. Our results suggest that changes in WBAC do not directly reflect absorbed dose, but may reflect radiation-induced biological damage at the systemic level. This study will contribute to the understanding of radiation-induced injuries and diseases, and will facilitate the establishment of biomarkers for radiation exposure.

The purpose of this work is to show the usefulness of a prediction method of tumor location based on partial least squares regression (PLSR) using multiple fiducial markers. The trajectory data of respiratory motion of four internal fiducial markers inserted in lungs were used for the analysis. The position of one of the four markers was assumed to be the tumor position and was predicted by other three fiducial markers. Regression coefficients for prediction of the position of the tumor-assumed marker from the fiducial markers’ positions is derived by PLSR. The tracking error and the gating error were evaluated assuming two possible variations. First, the variation of the position definition of the tumor and the markers on treatment planning computed tomograhy (CT) images. Second, the intra-fractional anatomical variation which leads the distance change between the tumor and markers during the course of treatment. For comparison, rigid predictions and ordinally multiple linear regression (MLR) predictions were also evaluated. The tracking and gating errors of PLSR prediction were smaller than those of other prediction methods. Ninety-fifth percentile of tracking/gating error in all trials were 3.7/4.1 mm, respectively in PLSR prediction for superior–inferior direction. The results suggested that PLSR prediction was robust to variations, and clinically applicable accuracy could be achievable for targeting tumors.

Temperature corrections are necessary to account for the varying mass of air in the cavity volume of a vented ionization chamber. The temporal response resulting from temperature changes in a cylindrical and/or Farmer-type ionization chamber, which is the standard dosimeter, has been thoroughly discussed by some researchers. The purpose of this study was to characterise and analyse the dependence of the cavity air temperature of the parallel-plate-type ionization chamber on changes in the ambient temperature. Ionization chambers NACP-02 (IBA Dosimetry, GmbH) and Advanced Markus TN34045 (PTW, Freiburg) were modelled using thermal analysis software to present the temperature equilibrium time and the entire ionization chamber temperature distribution. The temporal response of each ionization chamber was measured for comparing the calculation results of the thermal analysis. The ionization chamber cavities of NACP-02 and TN34045 reached complete equilibrium in 670 and 750 s, respectively. Heat transfer occurred faster at the centre of the front wall of TN34045 than at the outside of the centre except for the edges. Further, the non-uniformity of temperature in the cavity was in the range of 24.2–24.8°C for NACP-02 and 23.7–24.4°C for TN34045 at 200 s after the ionization chamber was installed in the water phantom. The previous proposal to wait for about 15 mins after submerging the chamber in a water phantom before the measurement is demonstrated to be appropriate for parallel-plate-type ionization chambers.

In cervical cancer treatment, radiation therapy is selected based on the degree of tumor progression, and radiation oncologists are required to delineate tumor contours. To reduce the burden on radiation oncologists, an automatic segmentation of the tumor contours would prove useful. To the best of our knowledge, automatic tumor contour segmentation has rarely been applied to cervical cancer treatment. In this study, diffusion-weighted images (DWI) of 98 patients with cervical cancer were acquired. We trained an automatic tumor contour segmentation model using 2D U-Net and 3D U-Net to investigate the possibility of applying such a model to clinical practice. A total of 98 cases were employed for the training, and they were then predicted by swapping the training and test images. To predict tumor contours, six prediction images were obtained after six training sessions for one case. The six images were then summed and binarized to output a final image through automatic contour segmentation. For the evaluation, the Dice similarity coefficient (DSC) and Hausdorff distance (HD) was applied to analyze the difference between tumor contour delineation by radiation oncologists and the output image. The DSC ranged from 0.13 to 0.93 (median 0.83, mean 0.77). The cases with DSC

Radon inhalation decreases the level of lipid peroxide (LPO); this is attributed to the activation of antioxidative functions. This activation contributes to the beneficial effects of radon therapy, but there are no studies on the risks of radon therapy, such as DNA damage. We evaluated the effect of radon inhalation on DNA damage caused by oxidative stress and explored the underlying mechanisms. Mice were exposed to radon inhalation at concentrations of 2 or 20 kBq/m3 (for one, three, or 10 days). The 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels decreased in the brains of mice that inhaled 20 kBq/m3 radon for three days and in the kidneys of mice that inhaled 2 or 20 kBq/m3 radon for one, three or 10 days. The 8-OHdG levels in the small intestine decreased by approximately 20–40% (2 kBq/m3 for three days or 20 kBq/m3 for one, three or 10 days), but there were no significant differences in the 8-OHdG levels between mice that inhaled a sham treatment and those that inhaled radon. There was no significant change in the levels of 8-oxoguanine DNA glycosylase, which plays an important role in DNA repair. However, the level of Mn-superoxide dismutase (SOD) increased by 15–60% and 15–45% in the small intestine and kidney, respectively, following radon inhalation. These results suggest that Mn-SOD probably plays an important role in the inhibition of oxidative DNA damage.

The present study aimed to identify the mechanisms underlying the increase in vascular permeability in mouse skin following irradiation. The left ears of C3H mice were subjected to 2 and 15 Gy of radiation in a single exposure. At 24 h after irradiation, the ears were excised and tissue sections were stained with toluidine blue to assess mast cell degranulation. Vascular endothelial growth factor (VEGF) expression was assessed via immunohistochemistry and western blotting. Approximately 5% (3%–14%) (mean [95% CI]) of mast cells in the skin of control mice were degranulated; moreover, at 24 h after 2 Gy irradiation, this value increased to approximately 20% (17%–28%). Mast cell degranulation by 15 Gy irradiation (32% [24%–40%]) was greater than that by 2 Gy irradiation. Significant differences were observed in mast cell degranulation among the control, 2 Gy and 15 Gy groups (p = 0.012). Furthermore, VEGF-positive reactions were observed in the cytoplasm of scattered fibroblasts in the dermis. In immunohistochemistry tests, VEGF expression at 24 h after irradiation increased slightly in the 2 Gy group compared to that in the control group, whereas no difference in VEGF expression was observed in the 15 Gy group compared to that in the control group. Expression of VEGF in western blots was consistent with that in immunohistochemistry. In conclusion, mast cell degranulation was increased in mouse skin at 24 h after irradiation in a dose-dependent manner. In contrast, VEGF expression was slightly increased following only low-dose (2 Gy) irradiation.

This article analyzes the accuracy of needle track and dose of a 3-dimensional printing template (3DPT) in the treatment of thoracic tumor with radioactive I-125 seed implantation (RISI). A total of 28 patients were included. The technical process included: (i) preoperative CT positioning, (ii) preoperative planning design, (iii) 3DPT design and printing, (iv) 3DPT alignment, (v) puncture and seed implantation. The errors of needle position and dosimetric parameters were analyzed. A total of 318 needles were used. The mean errors in needle depth, needle insertion point, needle tip and needle angle were 0.52 ± 0.48 cm, 3.4 ± 1.7 mm, 4.4 ± 2.9 mm and 2.8 ± 1.7°, respectively. The differences between actual needle insertion angle and needle depth and those designed in the preoperative were statistically significant (p 0.05). Some dosimetric parameters of preoperative plans such as V100, V200, CI and HI were not consistent with that of preoperative plans, and the difference was statistically significant (p 0.05). We conclude that for thoracic tumors, even under the guidance of 3DPT, there will be errors. The plan should be optimized in real time during the operation.

Total body irradiation (TBI) with ovarian shielding is expected to preserve fertility among hematopoietic stem cell transplant (HSCT) patients with myeloablative TBI-based regimens. However, the radiation dose to the ovaries that preserves ovarian function in TBI remains poorly understood. Furthermore, it is uncertain whether the dose to the shielded organs is associated with relapse risk. Here, we retrospectively evaluated the relationship between fertility and the dose to the ovaries, and between relapse risk and the dose to the pelvic bones. A total of 20 patients (median age, 23 years) with standard-risk hematologic diseases were included. Median follow-up duration was 31.9 months. The TBI prescribed dose was 12 Gy in six fractions for three days. Patients’ ovaries were shielded with cylinder-type lead blocks. The dose–volume parameters (D98% and Dmean) in the ovaries and the pelvic bones were extracted from the dose–volume histogram (DVH). The mean ovary Dmean for all patients was 2.4 Gy, and 18 patients recovered menstruation (90%). The mean ovary Dmean for patients with menstrual recovery and without recovery were 2.4 Gy and 2.4 Gy, respectively, with no significant difference (P = 0.998). Hematological relapse was observed in five patients. The mean pelvis Dmean and pelvis D98% for relapse and non-relapse patients were 11.6 Gy and 11.7 Gy and 5.6 Gy and 5.3 Gy, respectively. Both parameters showed no significant difference (P = 0.827, 0.807). In conclusion, TBI with ovarian shielding reduced the radiation dose to the ovaries to 2.4 Gy, and preserved fertility without increasing the risk of relapse.

The mammalian target of rapamycin (mTOR) is a sensor of nutrient status and plays an important role in cell growth and metabolism. Although inhibition of mTOR signaling promotes tumor cell death and several mTOR inhibitors have been used clinically, recent reports have shown that co-treatment with MHY1485, an mTOR activator, enhances the anti-cancer effects of anti-PD-1 antibody and 5-fluorouracil. However, it remains unclear whether MHY1485 treatment alters the effects of radiation on tumor cells. In this study, the radiosensitizing effects of MHY1485 were investigated using murine CT26 and LLC cell lines. We examined mTOR signaling, tumor cell growth, colony formation, apoptosis, senescence, oxidative stress, p21 accumulation and endoplasmic reticulum (ER) stress levels in cells treated with MHY1485 and radiation, either alone or together. We found that MHY1485 treatment inhibited growth and colony formation in both cell lines under irradiation and no-irradiation conditions, results that were not fully consistent with MHY1485’s known role in activating mTOR signaling. Furthermore, we found that combined treatment with MHY1485 and radiation significantly increased apoptosis and senescence in tumor cells in association with oxidative stress, ER stress and p21 stabilization, compared to radiation treatment alone. Our results suggested that MHY1485 enhances the radiosensitivity of tumor cells by a mechanism that may differ from MHY1485’s role in mTOR activation.

The feasibility of intensity modulated radiotherapy (IMRT) with involved field radiotherapy (IFRT) for Japanese patients with locally advanced non-small cell lung cancer (LA-NSCLC) remains unclear. Here we reviewed our initial experience of IMRT with IFRT for Japanese patients with LA-NSCLC to evaluate the feasibility of the treatment. Twenty LA-NSCLC patients who were treated with IMRT with IFRT during November 2019 to October 2020 were retrospectively analyzed. All patients received 60 Gy in 30 fractions of IMRT and were administered concurrent platinum-based chemotherapy. The median patient age was 71 years old and the group included 15 men and 5 women. The patient group included 2 patients with stage IIB, 11 patients with stage IIIA, 5 patients with stage IIIB, and 2 patients with stage IIIC disease. Histological diagnosis was squamous cell carcinoma in 14 patients, adenocarcinoma in 5 patients, and non-small cell lung cancer in 1 patient. The median follow-up period was 8 months. The incidence of grade 3 or greater pneumonitis was 5%, and grade 3 or greater esophagitis was not observed. None of the patients developed regional lymph node, with only recurrence reported so far. These findings indicate that IMRT with IFRT for Japanese patients with LA-NSCLC is feasible in terms of acute toxicity. Further study with a larger number of patients and longer follow-up to clarify the effect of treatment on patient prognosis is required.

We attempted to re-evaluate the efficacy of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) with more recent data. A total of 179 patients with LS-SCLC received radical thoracic radiotherapy and chemotherapy at our institution between 1998 and 2018. One hundred twenty-eight patients who achieved complete response (CR), good partial response (PR), and PR without progression for at least for one year after initial therapy were enrolled in this study. These patients were divided into a PCI group (group A, n = 43), and a non-PCI group (group B, n = 85). Survival outcomes were retrospectively evaluated. Because several background factors differed significantly between groups A and B, propensity score (PS) matching was performed as 1:1 match of the two groups. Finally, we analyzed 64 patients (group A/B = 32/32). Median follow-up periods were 53 and 31 months in groups A and B, respectively. There were no significant differences between the groups’ backgrounds. Two-year overall survival (OS) rates were 77% in group A and 62% in group B (p = 0.224). Two-year brain metastasis free survival (BMFS) rates were 85% in group A and 57% in group B (p = 0.008). The number of patients who underwent a brain imaging test for confirmation of no brain metastasis (BM) after radical thoracic radiotherapy and chemotherapy (before PCI) was 84 (group A/B = 32/52). A PS matched analysis for cases of pre-PCI brain imaging group, two-year OS rates for group A/B were 73/59% (p = 0.446). Two-year BMFS rates for group A/B were 91/52% (p = 0.021). Retrospectively, PS matched analysis revealed that adding PCI to LS-SCLC patients who achieved good thoracic control significantly improved BMFS, but OS did not improve.

To the best of our knowledge there have been no randomized controlled trials comparing lobectomy—a standard treatment for patients with early-stage non-small cell lung cancer (NSCLC)—and particle beam therapy (PBT), the best performing existing radiotherapy. We conducted a virtual randomized trial in medically operable patients with stage IA NSCLC to compare lobectomy and PBT effectiveness. A Markov model was developed to predict life expectancy after lobectomy and PBT in a cohort of patients with stage IA NSCLC. Ten thousand virtual patients were randomly assigned to each group. Sensitivity analyses were performed as model variables and scenarios changed to determine which treatment strategy was best for improving life expectancy. All estimated model parameters were determined using variables extracted from a systematic literature review of previously published articles. The preferred strategy differed depending on patient age. In young patients, lobectomy showed better life expectancy than that of PBT. The difference in life expectancy between lobectomy and PBT was statistically insignificant in older patients. Our model predicted lobectomy as the preferred strategy when operative mortality was under 5%. However, the preferred strategy changed to PBT if operative mortality post lobectomy was over 5%. For medically operable patients with stage IA NSCLC, our Markov model revealed the preferred strategy of lobectomy or PBT regarding operative mortality changed with varying age and comorbidity. Until randomized controlled trial results become available, we hope the current results will provide a rationale background for clinicians to decide treatment modalities for patients with stage IA NSCLC.

X-ray induced molecular luminescence (XML) is a phenomenon that can be utilized for clinical, deep-tissue functional imaging of tailored molecular probes. In this study, a survey of common or clinically approved fluorophores was carried out for their megavoltage X-ray induced excitation and emission characteristics. We find that direct scintillation effects and Cherenkov generation are two possible ways to cause these molecules’ excitation. To distinguish the contributions of each excitation mechanism, we exploited the dependency of Cherenkov radiation yield on X-ray energy. The probes were irradiated by constant dose of 6 MV and 18 MV X-ray radiation, and their relative emission intensities and spectra were quantified for each X-ray energy pair. From the ratios of XML, yield for 6 MV and 18 MV irradiation we found that the Cherenkov radiation dominated as an excitation mechanism, except for aluminum phthalocyanine, which exhibited substantial scintillation. The highest emission yields were detected from fluorescein, proflavin and aluminum phthalocyanine, in that order. XML yield was found to be affected by the emission quantum yield, overlap of the fluorescence excitation and Cherenkov emission spectra, scintillation yield. Considering all these factors and XML emission spectrum respective to tissue optical window, aluminum phthalocyanine offers the best XML yield for deep tissue use, while fluorescein and proflavine are most useful for subcutaneous or superficial use.

It is often challenging to determine the accurate size and shape of oral lesions through computed tomography (CT) or magnetic resonance imaging (MRI) when they are very small or obscured by metallic artifacts, such as dental prostheses. Intraoral ultrasonography (IUS) has been shown to be beneficial in obtaining precise information about total tumor extension, as well as the exact location and guiding the insertion of catheters during interstitial brachytherapy. We evaluated the role of IUS in assessing the clinical outcomes of interstitial brachytherapy with 198Au grains in tongue cancer through a retrospective medical chart review. The data from 45 patients with T1 (n = 21) and T2 (n = 24) tongue cancer, who were mainly treated with 198Au grain implants between January 2005 and April 2019, were included in this study. 198Au grain implantations were carried out, and positioning of the implants was confirmed by IUS, to ensure that 198Au grains were appropriately placed for the deep border of the tongue lesion. The five-year local control rates of T1 and T2 tongue cancers were 95.2% and 95.5%, respectively. We propose that the use of IUS to identify the extent of lesions and the position of implanted grains is effective when performing brachytherapy with 198Au grains.

We investigated the prognostic significance and treatment outcomes of pretreatment inflammatory response markers for locally advanced squamous cell carcinoma (SCC) of the external auditory canal (EAC) and middle ear (ME). Between July 2003 and July 2019, 21 patients with SCC of the EAC (n = 18) or ME (n = 3) who received radiotherapy with or without surgery or systemic therapy (radiotherapy alone [n = 2], radiotherapy + systemic therapy [n = 6], radiotherapy + surgery [n = 7], radiotherapy + surgery + systemic therapy [n = 6]) were retrospectively examined. The median radiation dose was 66.0 (range, 50.4–70.0) Gy, with daily fractions of 1.8–2.0 Gy. The median follow-up period was 25 months (range, 6–137). The two-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) rates were 61%, 48%, and 55%, respectively. OS, PFS, and LC did not differ significantly according to patient- (age, sex), tumor- (Pittsburgh stage, pretreatment neurological findings), and treatment-related (surgery or systemic therapy, radiation dose, prophylactic neck irradiation) factors. Conversely, there were significant differences in OS, PFS, and LC between patients with high and low pretreatment C-reactive protein-to-albumin ratios (p = 0.002, 0.003, and 0.004, respectively). OS also differed significantly between patients with high and low pretreatment neutrophil-to-lymphocyte ratios (NLR; p = 0.037). Other inflammatory response markers, including platelet-to-lymphocyte ratio (PLR) and albumin-to-globulin ratio (AGR), did not influence OS, PFS, or LC. Our findings suggest that pretreatment C-reactive protein-to-albumin ratio and NLRs have a significant impact on treatment outcomes in patients with locally advanced SCC of the EAC and ME.

The retrospective dosimetry that follows accidental X-ray exposure is becoming more significant for improving radiation diagnosis and treatment. We investigated the dosimetric properties of electron spin resonance (ESR) signals in X-ray irradiated fingernails under conditions that resemble realistic situations. We collected fingernails from 12 Japanese donors between the ages of 30 to 70. The sampled fingernails were utilized for X-ray irradiation, mechanical stimulation and background measurements. We also collected 10 toenails from one of the donors to evaluate their differences from fingernails. Additionally, we prepared 15 samples from two donors to compare the signals generated by γ-rays to those by X-rays. After observing the linear dose–response for both X- and γ-ray irradiated samples, we found that the sensitivity of the air-absorbed dose of γ-ray irradiated samples was identical to that of X-ray irradiated samples. The effect from secondary electrons seemed to be small in fingernails. The inter-individual variation in the sensitivity was no greater than the intra-individual variation. The signal intensities in each measurement fluctuated about the linear response curve, and the size of the fluctuation was dependent on the sample. The average fluctuation corresponded to 1.7 Gy, and the standard deviation was 1.3 Gy. The signal induced by X-rays could be erased by soaking the samples in water and subsequently drying them for four days, which allowed us to estimate the signal intensity prior to the exposure. These characteristics of the ESR signal induced by X-rays facilitate the development of a feasible protocol for fingernail dose reconstruction.

In order to respond to nuclear or radiological emergencies effectively and protect the physical and mental health of the public, the national-, provincial-, municipal- and county-level public health response systems for nuclear or radiological emergencies had been established in China by the end of twentieth century. The health administrative departments at all levels have established professional emergency response teams, continue to improve their own level of emergency response systems and operating mechanisms, enhance the capabilities of radiation injury treatment, radiation monitoring and protection through training and exercises and also pay attention to the logistical support for emergency response. In this article the organizations, management system and capabilities of public health response to nuclear or radiological emergencies in China are briefly introduced. We try to strengthen information exchange and cooperation with foreign counterparts in this field in the future, so as to jointly promote the development of preparedness and response for nuclear or radiological emergencies.

Radiation therapy is generally effective for treating breast cancers. However, approximately 30% of patients with breast cancer experience occasional post-treatment local and distant metastasis. Low-dose (0.5 Gy) irradiation is a risk factor that promotes the invasiveness of breast cancers. Although an inhibitor of checkpoint kinase 1 (Chk1) suppresses the growth and motility of breast cancer cell lines, no study has investigated the effects of the combined use of a Chk1 inhibitor and radiation on cancer metastasis. Here, we addressed this question by treating the human breast cancer cell line MDA-MB-231 (in vitro) and mouse mammary tumor cell line 4 T1 (in vitro and in vivo) with γ-irradiation and the Chk1 inhibitor PD407824. Low-dose γ-irradiation promoted invasiveness, which was suppressed by PD407824. Comprehensive gene expression analysis revealed that low-dose γ-irradiation upregulated the mRNA and protein levels of S100A4, the both of which were downregulated by PD407824. We conclude that PD407824 suppresses the expression of S100A4. As the result, γ-irradiation-induced cell invasiveness were inhibited.

The objective of the study was to describe cellular and molecular markers of radioprotection by anisomycin, focusing on the changes in rat brain tissue. Two-month-old Wistar rats were exposed to a 60Co radiation source at a dose of 6 Gy, with or without radioprotection with anisomycin (150 mg/kg) administered subcutaneously 30 min before or 3 or 6 h after irradiation. Survivors were analyzed 30 days after treatment. Astroglial and microglial responses were investigated based on the expression of glial markers assessed with immunohistochemistry, and quantitative changes in brain biomolecules were investigated by Raman microspectroscopy. In addition, blood plasma levels of pro-inflammatory (interleukin 6 and tumor necrosis factor α) and anti-inflammatory (interleukin 10) cytokines were assessed. We found that application of anisomycin either before or after irradiation significantly decreased the expression of the microglial marker Iba-1. We also found an increased intensity of Raman spectral bands related to nucleic acids, as well as an increased level of cytokines when anisomycin was applied after irradiation. This suggests that the radioprotective effects of anisomycin are by decreasing Iba-1 expression and stabilizing genetic material by increasing the level of nucleic acids.

We aimed to predict the minimum distance between a tumor and the gastrointestinal (GI) tract that can satisfy the dose constraint by creating simulation plans with carbon-ion (C-ion) radiotherapy (RT) and photon RT for each case assuming insertion of virtual spacers of various thicknesses. We enrolled 55 patients with a pelvic tumor adjacent to the GI tract. Virtual spacers were defined as the overlap volume between the GI tract and the volume expanded 7–17 mm from the gross tumor volume (GTV). Simulation plans (70 Gy in 35 fractions for at least 95% of the planning target volume [PTV]) were created with the lowest possible dose to the GI tract under conditions that meet the dose constraints of the PTV. We defined the minimum thickness of virtual spacers meeting D2 cc of the GI tract

The Radiation Effects Research Foundation (RERF) is the primary organization in Japan dedicated to studying the health consequences of the Hiroshima and Nagasaki atomic bombings in World War II. In December 2020, RERF held a virtual international workshop on the ethical, legal and social implications (ELSI) of genome studies. In this workshop, the ELSI considerations of future human genome studies on radiation research including atomic bomb survivors and their families were discussed. Since genome sequencing (GS) is now practical and affordable, RERF now plans GS of parents/child trios to examine genetic effects of atomic bomb radiation. As such studies may engender some novel risks and benefits, ethics review and engagement with families (including consent) need to be considered. These include protection of individual privacy, use of samples from deceased prior participants, return of results to the participants, public sharing of genome data and advance science and social welfare. Specifically with regard to social welfare, the results of such studies may have implications for public and government decision-making regarding social benefits of victims and other important questions. Based on these broad-ranging discussions we have developed the following concepts to guide this work: “trust,” “compromise” and “relationship building,” inclusive of the concerned stakeholders, scientific aims and Japanese society at large. We conclude that in order to realize, establish and maintain these concepts, it is essential to put procedures into place to ensure the successful, consensus-based implementation of the RERF studies.

Ionizing radiation-induced oxidation and formation of deoxyribonucleic acid (DNA) double strand breaks (DSBs) are considered the exemplar of genetic lesions. Guanine bases are most prone to be oxidized when DNA and Ribonucleic acid (RNA) are damaged. The repair processes that are initiated to correct this damage release multiple oxidized guanine species into the urine. Hence, the excretion of guanine species can be related with the total repair process. Our study quantified the total DSBs formation and the amount of guanine species in urine to understand the DNA break and repair process after whole body (WB) exposure to 18F-FDG positron emission tomography/computed tomography (PET/CT). A total of 37 human participants were included with control and test groups and the average radiation dose was 27.50 ± 2.91 mSv. γ-H2AX foci assay in the collected blood samples was performed to assess the DSBs, and excreted guanine species in urine were analyzed by a competitive ELISA method. We observed a significant increase of DNA damage that correlated well with the increasing dose (p-value 0.009) and body weight (p-value 0.05). In the test group, excreted guanine species in urine sample significantly increased (from 24.29 ± 5.82 to 33.66 ± 7.20 mg/mmol creatinine). A minimum (r2 = 0.0488) correlation was observed between DSBs formation and excreted guanine species. A significant difference of DNA damage and 8-OHdG formation was seen in the test group compared to controls. Larger population studies are needed to confirm these observations, describe the fine-scale timing of changes in the biomarker levels after exposure, and further clarify any potential risks to patients from PET/CT procedures.

The accurate measurement of the 3D dose distribution of carbon-ion beams is essential for safe carbon-ion therapy. Although ionization chambers scanned in a water tank or air are conventionally used for this purpose, these measurement methods are time-consuming. We thus developed a rapid 3D dose-measurement tool that employs a silver-activated zinc sulfide (ZnS) scintillator with lower linear energy transfer (LET) dependence than gadolinium-based (Gd) scintillators; this tool enables the measurement of carbon-ion beams with small corrections. A ZnS scintillator sheet was placed vertical to the beam axis and installed in a shaded box. Scintillation images produced by incident carbon-ions were reflected with a mirror and captured with a charge-coupled device (CCD) camera. A 290 MeV/nucleon mono-energetic beam and spread-out Bragg peak (SOBP) carbon-ion passive beams were delivered at the Gunma University Heavy Ion Medical Center. A water tank was installed above the scintillator with the water level remotely adjusted to the measurement depth. Images were recorded at various water depths and stacked in the depth direction to create 3D scintillation images. Depth and lateral profiles were analyzed from the images. The ZnS-scintillator-measured depth profile agreed with the depth dose measured using an ionization chamber, outperforming the conventional Gd-based scintillator. Measurements were realized with smaller corrections for a carbon-ion beam with a higher LET than a proton. Lateral profiles at the entrance and the Bragg peak depths could be measured with this tool. The proposed method would make it possible to rapidly perform 3D dose-distribution measurements of carbon-ion beams with smaller quenching corrections.

DNA double-strand breaks (DSBs) induced by ionizing radiation are the major cause of cell death, leading to tissue/organ injuries, which is a fundamental mechanism underlying the development of tissue reaction. Since unscheduled senescence, predominantly induced among epithelial tissues/organs, is one of the major modes of cell death in response to radiation exposure, its role in tissue reaction has been extensively studied, and it has become clear that senescence-mediated secretion of soluble factors is an indispensable component of the manifestation of tissue reaction. Recently, an unexpected link between cytoplasmic DSBs and innate immunity was discovered. The activation of cyclic GMP-AMP (cGAMP) synthase (cGAS) results in the stimulation of the cGAS–stimulator of interferon genes (STING) pathway, which has been shown to regulate the transactivation of a variety of secretory factors that are the same as those secreted from senescent cells. Furthermore, it has been proven that cGAS–STING pathway also mediates execution of the senescence process by itself. Hence, an autocrine/paracrine feedback loop has been discussed in previous literature in relation to its effect on the tissue microenvironment. As the tissue microenvironment plays a crucial role in cancer development, tissue reaction could be involved in the late health effects caused by radiation exposure. In this paper, the novel findings in radiation biology, which should provide a better understanding of the mechanisms underlying radiation-induced carcinogenesis, are overviewed., Journal of Radiation Research, 62(S1), pp. i30-i35; 2021

In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5–D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%—2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: −0.5%—0.7%). The mean differences of D99, D5–D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.

The Fukushima Daiichi Nuclear Power Station (NPS) accident, which occurred in March 2011, is having long-term effects on children. About 3 years after the accident, we identified three patterns of peer relationship problems and four patterns of emotional symptoms using group-based trajectory modeling. As a result, we reported that different factors might be related to very severe trajectories of peer relationship problems and emotional symptoms. In this study, we used five waves of data from fiscal year (FY) 2011 to FY2015 from the Mental Health and Lifestyle Survey, a detailed survey of the Fukushima Health Management Survey started in FY2011. We analyzed 7013 residents within the government-designated evacuation zone (aged 6–12 years old as of 11 March 2011) with responses to all items of psychological distress in at least one wave from FY2011 and FY2015. We planned this study to describe the trajectories of peer relationship problems and emotional symptoms in children and to examine potential risks and protective factors over the 5 years following the NPS accident. We identified four patterns of peer relationship problems and five patterns of emotional symptoms using latent class growth analysis. For peer relationship problems, male sex, experiencing the NPS explosion and lack of exercise habits were associated with the severe trajectory group. For emotional symptoms, experiencing the NPS explosion, experiencing the tsunami disaster and lack of exercise habits were associated with the severe trajectory group. Exercise habits are very important for the mental health of evacuees after a nuclear disaster.

We propose a two-step method to converse human tissue materials from patient computed tomography (CT) images, which is required in dose reconstructions for a retrospective study of carbon-ion radiotherapy (CIRT) using Monte Carlo (MC) simulation. The first step was to assign the standard tissues of the International Commission on Radiological Protection reference phantoms according to the CT-number. The second step was to determine the mass density of each material based on the relationship between CT-number and stopping power ratio (Hounsfield unit [HU]-SPR) registered in treatment planning system (TPS). Direct implementation of the well-calibrated HU-SPR curve allows the reproduction of previous clinical treatments recorded in TPS without uncertainty due to a mismatch of the CT scanner or scanning conditions, whereas MC simulation with realistic human tissue materials can fulfill the out-of-field dose, which was missing in the record. To validate our proposed method, depth-dose distributions in the homogenous and heterogeneous phantoms irradiated by a 400 MeV/u carbon beam with an 8 cm spread-out Bragg peak (SOBP) were computed by the MC simulation in combination with the proposed methods and compared with those of TPS. Good agreement of the depth-dose distributions between the TPS and MC simulation (within a 1% discrepancy in range) was obtained for different materials. In contrast, fluence distributions of secondary particles revealed the necessity of MC simulation using realistic human tissue. The proposed material assignment method will be used for a retrospective study using previous clinical data of CIRT at the National Institute of Radiological Sciences (NIRS).

After the Fukushima Dai-ichi Nuclear Power Station (FDNPS) accident in 2011, radiation-related risk of childhood thyroid cancer remains a matter of concern among residents living in areas affected by radioactive plumes. As a countermeasure to that, the Fukushima Prefectural Government—in conjunction with Fukushima Medical University—began the Fukushima Thyroid Examination (FTE) campaign in 2011. As 116 definite or suspected thyroid cancer cases were found after the first round of FTE and the total number of cases was >240 as of June 2020, residents’ concerns have deepened. Some researchers claim that these cases are radiation-induced, while others claim a screening effect (because FTE uses high-resolution ultrasound equipment) and express concern about over-diagnosis. Researchers therefore must address two conflicting issues: one is to elucidate radiation effects on thyroid cancer, which requires continuation of FTE; the other is to solve ethical problems associated with FTE. As to over-diagnosis, surgeons claim that early diagnosis benefits children by reducing the side-effects of treatment and prolonging disease-free survival, while cancer epidemiologists claim that early diagnosis will result in overtreatment without reducing the death rate. ‘To receive FTE or not’ and ‘to stop FTE or not’ are ongoing dilemmas for children (and their parents) and other stakeholders, respectively. To facilitate building a consensus among stakeholders, I overview recent findings about dose reconstruction, the dose–response relationship of thyroid cancer, over-diagnosis, and the natural history of thyroid cancer, all of which contribute to judging the risk–benefit balance of thyroid screening.

The effect of exercise habits on the increased incidence of lifestyle-related diseases among residents of the evacuation area in Fukushima Prefecture after the Great East Japan Earthquake is not well characterized. This study examined the influence of exercise habits on the frequency of new onset of lifestyle-related diseases in the aftermath of the earthquake using data from the Fukushima Health Management Survey (FHMS). Of the 32 289 individuals (14 004 men and 18 285 women) aged 40–90 years who underwent one or more health examinations in both 2011–12 and 2014–15, those who knew whether they had any lifestyle diseases and who responded to a questionnaire about their exercise and physical activity habits were included (dyslipidemia, 8017; hypertension, 7173; and diabetes mellitus, 13140 individuals). The association between the frequency of new onset of lifestyle-related diseases in 2014–15 and the presence or absence of persistent exercise and physical activity habits (active lifestyle) was examined using the FHMS data. The frequency of new onset of dyslipidemia was significantly lower in the active lifestyle group than in the sedentary lifestyle group (P = 0.008). On univariate and multivariate logistic regression analyses, the presence of active lifestyle, obesity and the experience of evacuation showed a significant association with new onset of dyslipidemia, independent of age, sex or follow-up period. Thus maintaining physical activity and exercise habits may help prevent the new onset of dyslipidemia among residents of the evacuation area in the Fukushima Prefecture after the earthquake.

Cumulative dose effects, which are one of the main causes of errors that occur when an implantable cardiac pacemaker (ICP) is irradiated with ionizing radiation, induce permanent failure in ICPs. Although flattening filter free (FFF) beams, which are often used in stereotactic radiotherapy, are known to have different characteristics from conventional (with flattening filter [WFF]) beams, the cumulative dose effects on ICPs with FFF beams have been under-investigated. This study investigates ICP failure induced by cumulative dose effects of FFF beams. When the ICP placed in the center of the irradiation field was irradiated with 10 MV-FFF at 24 Gy/min, the cumulative dose at which failure occurred was evaluated on the basis of the failure criteria associated with high cumulative dose as described in the American Association of Physicists in Medicine Task Group 203. The ICP failures such as a mild battery depletion at a cumulative dose of 10 Gy, pacing-output voltage change >25% at a cumulative dose of 122 Gy, and the loss of telemetry capability at cumulative dose 134 Gy were induced by cumulative dose effects. The cumulative doses by which the cumulative dose effects of FFF beams induced ICP failure were not very different from those reported in previous studies with WFF beams. Therefore, radiotherapy with FFF beams (and WFF beams) for patients with ICP requires appropriate management for minimizing the cumulative dose effects.

We developed a confidence interval-(CI) assessing model in multivariable normal tissue complication probability (NTCP) modeling for predicting radiation-induced liver disease (RILD) in primary liver cancer patients using clinical and dosimetric data. Both the mean NTCP and difference in the mean NTCP (ΔNTCP) between two treatment plans of different radiotherapy modalities were further evaluated and their CIs were assessed. Clinical data were retrospectively reviewed in 322 patients with hepatocellular carcinoma (n = 215) and intrahepatic cholangiocarcinoma (n = 107) treated with photon therapy. Dose–volume histograms of normal liver were reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose. The most predictive variables were used to build the model based on multivariable logistic regression analysis with bootstrapping. Internal validation was performed using the cross-validation leave-one-out method. Both the mean NTCP and the mean ΔNTCP with 95% CIs were calculated from computationally generated multivariate random sets of NTCP model parameters using variance–covariance matrix information. RILD occurred in 108/322 patients (33.5%). The NTCP model with three clinical and one dosimetric parameter (tumor type, Child–Pugh class, hepatitis infection status and MLD) was most predictive, with an area under the receiver operative characteristics curve (AUC) of 0.79 (95% CI 0.74–0.84). In eight clinical subgroups based on the three clinical parameters, both the mean NTCP and the mean ΔNTCP with 95% CIs were able to be estimated computationally. The multivariable NTCP model with the assessment of 95% CIs has potential to improve the reliability of the NTCP model-based approach to select the appropriate radiotherapy modality for each patient.

It is held that the skin dose from radon progeny is not negligibly small and that introducing cancer is a possible consequence under normal circumstances as there are a number of uncertainties in terms of related parameters such as activity concentrations in air and water, target cells in skin, skin covering materials, and deposition velocities. An interesting proposal has emerged in that skin exposure to natural radon-rich thermal water as part of balneotherapy can produce an immune response to induce beneficial health effects. The goal of this study was to obtain generic dose coefficients with a focus on the radon progeny deposited on the skin in air or water in relation to risk or treatment assessments. We thus first estimated the skin deposition velocities of radon progeny in air and thermal water based on data from the latest human studies. Skin dosimetry was then performed under different assumptions regarding alpha-emitting source position and target cell (i.e. basal cells or Langerhans cells). Furthermore, the impact of the radon progeny deposition on effective doses from all exposure pathways relating to ‘radon exposure’ was assessed using various possible scenarios. It was found that in both exposure media, effective doses from radon progeny inhalation are one to four orders of magnitude higher than those from the other pathways. In addition, absorbed doses on the skin can be the highest among all pathways when the radon activity concentrations in water are two or more orders of magnitude higher than those in air.

In the event of a nuclear accident or radiological emergency, effective communication with the public on radiation risks is important in order to contain and rein in damage to physical and mental health, and social and economic consequences. The purpose of this paper is to summarize features of trustworthy sources of scientific information, and to convey their importance in radiation risk communication by recalling other aspects influencing the effectiveness of that communication. This will draw on key references in the literature, augmented with some experience and insight gleaned from a professional career of more than 35 years at the national and international level, including contributing to the International Atomic Energy Agency’s (IAEA) work on the consequences of the Chernobyl accident (1990–1995), heading its incident and emergency centre (1996–2005), and as the secretary (2005–2018) of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), which conducts scientific reviews on the levels and effects of radiation exposure. The paper highlights the necessity of sound science and trustworthy sources, and recapitulates the main elements needed both to ensure solid conclusions on radiation epidemiology and to foster trust. The paper concludes that, while sound science and trustworthy sources are necessary, they are in themselves to a greater or lesser degree insufficient to ensure fully effective risk communication. Some of the major problems in communicating this science are highlighted to help others charged with preparing for and conducting this onerous task in the future.

Intrinsic autophagy is important for the maintenance of intestinal homeostasis and intestinal regeneration. Ionizing radiation suppresses intrinsic autophagy and reduces damage-induced regeneration in the intestine, resulting in intestinal injury. Resveratrol, a sirtuin 1 (SIRT1) agonist, promotes autophagy and exerts radioprotective effect. In this study, the protective effect of resveratrol against radiation-induced intestinal injury and its potential mechanism were investigated. Intestinal epithelial cells (IEC-6) were exposed to 10 Gy ionizing radiation and resveratrol (0.1–40.0 μM). Cell viability was investigated using Cell Counting Kit 8 (CCK8), apoptosis was observed by Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and flow cytometry, and the expression of apoptotic and autophagic proteins was determined by western blotting. Resveratrol exerted a high toxicity against IEC-6 cells, but at low concentrations, it inhibited ionizing radiation-induced apoptosis. Resveratrol increased SIRT1 expression after irradiation and inhibited ionizing radiation-induced p53 acetylation and pro-apoptotic protein, Bax, expression. Furthermore, resveratrol promoted autophagy via the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, thereby protecting IEC-6 cells against radiation-induced damage. These results suggest that resveratrol reduces radiation-induced IEC-6 cell damage by inhibiting apoptosis and promoting autophagy via the activation of SIRT1, and that the PI3K/AKT/mTOR signaling pathway is involved in the induction of autophagy.

A post-exposure cohort study in Hiroshima and Nagasaki reported that low-dose exposure to radiation heightened the risk of cardiovascular diseases (CVD), such as stroke and myocardial infarction, by 14–18% per Gy. Moreover, the risk of atherosclerosis in the coronary arteries reportedly increases with radiation therapy of the chest, including breast and lung cancer treatment. Cellular senescence of vascular endothelial cells (ECs) is believed to play an important role in radiation-induced CVDs. The molecular mechanism of age-related cellular senescence is believed to involve genomic instability and DNA damage response (DDR); the chronic inflammation associated with senescence causes cardiovascular damage. Therefore, vascular endothelial cell senescence is believed to induce the pathogenesis of CVDs after radiation exposure. The findings of several prior studies have revealed that ionizing radiation (IR) induces cellular senescence as well as cell death in ECs. We have previously reported that DDR activates endothelial nitric oxide (NO) synthase, and NO production promotes endothelial senescence. Endothelial NO synthase (eNOS) is a major isoform expressed in ECs that maintains cardiovascular homeostasis. Therefore, radiation-induced NO production, a component of the DDR in ECs, may be involved in CVDs after radiation exposure. In this article, we describe the pathology of radiation-induced CVD and the unique radio-response to radiation exposure in ECs.

The particle irradiation data ensemble (PIDE) is the largest database of cell survival data measured after exposure to ion beams and photon reference radiation. We report here on the updated version of the PIDE database and demonstrate how to investigate generic properties of radiation dose response using these sets of raw data. The database now contains information of over 1100 pairs of photon and ion dose response curves. It provides the originally published raw data of cell survival in addition to given linear quadratic (LQ) model parameters. If available, the raw data were used to derive LQ model parameters in the same way for all experiments. To demonstrate the extent of the database and the variability among experiments we focus on the dose response curves after ion and photon radiation separately in a first step. Furthermore, we discuss the capability and the limitations of the database for analyzing properties of low and high linear energy transfer (LET) radiation response based on multiple experiments. PIDE is freely available to the research community under www.gsi.de/bio-pide.

The purpose of this study was to evaluate the effect of dose rate to the rectum on late rectal complications in patients treated with computed tomography (CT)-based image-guided brachytherapy (IGBT) for cervical cancer. The subjects were 142 patients with cervical cancer who underwent Ir-192 high-dose-rate (HDR)-IGBT between March 2012 and January 2018. The dose rate to the rectum was calculated using in-house software. The minimum, mean and maximum effective dose rate (EDR) was calculated for voxels of the rectal volume covered by cumulative doses >D0.1cc, >D2cc, and > D5cc. The average EDR of three to four brachytherapy sessions was calculated (EDR for patients; EDRp). The total dose of the rectum was calculated as the biologically equivalent dose in 2-Gy fractions (EQD2). The associations between EDRp for D0.1cc, D2cc, and D5cc and the respective rectal EQD2 values with late rectal complications were then analyzed. The median follow-up period was 40 months. Patients with rectal complications of ≥Grade 1 received a significantly higher mean EDRp for D0.1cc–5cc and had a greater EQD2 for D0.1cc–5cc. Multivariate analysis was performed using the mean EDRp for D2cc, EQD2 for D2cc, heavy smoking and BMI. Of these four variables, mean EDRp for D2cc (HR = 3.38, p = 0.004) and EQD2 for D2cc (HR = 2.59, p = 0.045) emerged as independent predictors for late rectal complications. In conclusion, mean EDRp and EQD2 were associated with late rectal complications in patients treated with HDR CT-based IGBT for cervical cancer.

The purpose of this retrospective study was to investigate survival outcomes and irradiated tumor control (local control [LC]) and locoregional control (LRC) after stereotactic body radiotherapy (SBRT) for T1 or recurrent T1 (rT1) kidney cancer. Twenty-nine nonconsecutive patients with 30 tumors were included. SBRT doses of 70 Gy, 60 Gy or 50 Gy in 10 fractions were prescribed with a linear accelerator using daily image guidance. The Kaplan–Meier method was used to estimate time-to-event outcomes, and the log-rank test was used to compare survival curves between groups divided by each possible factor. The median follow-up periods for all patients and survivors were 57 months and 69.6 months, respectively. The five-year LC rate, LRC rate, progression-free survival (PFS) rate, disease-specific survival (DSS) rate and overall survival (OS) rate were 94%, 88%, 50%, 96% and 68%, respectively. No significant factor was related to OS and PFS. Three of 24 non-hemodialysis (HD) patients had new-onset-HD because of the progression of underlying kidney disease. Grade 3 or higher toxicities from SBRT did not occur. In conclusion, SBRT for kidney cancer provided a high rate of LC, LRC and DSS with minimal toxicities, but patient selection and indication for SBRT should be done carefully considering the relatively low OS rate.

This study aimed to evaluate the long-term efficacy of proton beam therapy (PBT) for unresectable benign meningiomas at the University of Tsukuba, Japan. From 1986–1998, 10 patients were treated at the Particle Radiation Medical Science Center (PRMSC) with a relative biological effectiveness (RBE) value of 1.0 using an accelerator built for physics experiments. The total dose was compensated with an X-ray in three patients. Following that, from 2002–2017, 17 patients were treated with a RBE value of 1.1 at the Proton Medical Research Center (PMRC) which was built for medical use. At the PRMSC, the total dose ranged from 50.4–66 Gy (median: 54 Gy). During the follow-up, which lasted between 3.8 and 31.6 years (median: 25.1 years), the 5-, 10-, 15-, 20- and 30-year local control rates were 100%, and the 5-, 10-, 15-, 20- and 30-year survival rates were 90, 80, 70, 70 and 36%, respectively. One patient died of brainstem radiation necrosis 5.1 years after PBT. At PMRC, the total dose ranged from 45.0–61.2 GyE, with a median of 50.4 GyE. During the follow-up, which lasted between 3 and 17 years with a median of 10.5 years, the 5-, 10- and 15-year local control rates were 94.1%, and the 5-, 10- and 15-year survival rates were 100, 100 and 88.9%, respectively. Neither malignant transformation nor secondary malignancy was observed, indicating that fractionated PBT may be effective and safely control benign unresectable meningioma even for the lifelong period of time.