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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.

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.

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.

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

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.

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.

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.

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

It is crucial to evaluate ethical issues regarding evacuation orders, especially after a nuclear disaster. After the Fukushima accident in 2011, the Japanese government ordered the affected people to evacuate. The evacuation orders have now been lifted in many areas. A risk trade-off analysis between benefits and risk associated with returning home would help in evaluating the justification for the lifting of the evacuation order in the aftermath of a nuclear disaster. Here, we performed a risk trade-off analysis among people returning home after the lifting of an evacuation order between an increase in emotional happiness (positive effect) and loss of life expectancy due to additional radiation exposure (negative effect), using a happy life expectancy (HpLE) indicator. Emotional happiness was estimated using questionnaires distributed among the affected people who lived in municipalities where evacuation orders were lifted. Loss of life expectancy was estimated under a scenario that returnees received 20 mSv in the year of return and subsequent radiation exposure. Increase in emotional happiness due to returning home was ~1–2 orders of magnitude higher among women aged 20, 40 and 65 years than the loss of life expectancy due to additional radiation exposure. This finding has implications for the justification for the lifting of evacuation orders.

Hepatocellular carcinoma (HCC) located in the caudate lobe (caudate HCC) is rare; however, patients with this type of tumour have poorer prognoses than those with HCC in other segments. Despite many published reports on the clinical usefulness of proton beam therapy (PBT) for HCC, data on the clinical outcomes of patients undergoing PBT for caudate HCC remain scarce. Therefore, the present study aimed to investigate the outcomes of this group of patients. Thirty patients with caudate HCC who underwent definitive PBT between February 2002 and February 2014 were retrospectively analysed. The total irradiation doses ranged from 55 to 77 (median 72.6) Gy relative biological dose. The median follow-up period was 37.5 (range, 3.0–152.0) months. The overall survival (OS) rates at one, three and five years were 86.6%, 62.8% and 46.1%, respectively. According to univariate and multivariate analyses, Child-Pugh A (P

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.

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.

Apelin-13 and APJ are implicated in different key physiological processes. This work aims at exploring the radioprotective effect of fucoxanthin (FX) on γ-radiation (RAD)-induced changes in the apelin-13/APJ pathway, which causes damage in the liver, kidney, lung and spleen of mice. Mice were administered FX (10 mg kg–1 day–1, i.p) and exposed to γ-radiation (2.5 Gy week–1) for four consecutive weeks. The treatment of irradiated mice by FX resulted in a significant amendment in protein expression of the apelin-13/APJ/NF-κB signalling pathway concurrently with reduced hypoxia (hypoxia-inducible factor-1α), suppressed oxidative stress marker (malondialdehyde), enhanced antioxidant defence mechanisms (reduced glutathione and glutathione peroxidase), a modulated inflammatory response [interleukin-6 (IL-6), monocyte chemoattractant protein-1, IL-10 and α-7-nicotinic acetylcholine receptor) and ameliorated angiogenic regulators [matrix metalloproteinase (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1), as well as the tissue damage indicator (lactate dehydrogenase) in organ tissues. In addition, there were significant improvement in serum inflammatory markers tumour necrosis factor-α, IL-10, IL-1β and C-reactive protein compared with irradiated mice. The histopathological investigation of the FX + RAD organ tissues support the biochemical findings where the improvements in the tissues’ architecture were obvious when compared with those of RAD. FX was thus shown to have a noticeable radioprotective action mediated through its regulatory effect on the apelin-13/APJ/NF-κB signalling pathway attributed to its antioxidant and anti-inflammatory activity that was reflected in different physiological processes. It could be recommended to use FX in cases of radiation exposure to protect normal tissues.

Metformin, a first-line oral drug for type II diabetes mellitus, not only reduces blood glucose levels, but also has many other biological effects. Recent studies have been conducted to determine the protective effect of metformin in irradiation injuries. However, the results are controversial and mainly focus on the time of metformin administration. In this study, we aimed to investigate the protective effect of metformin in BALB/c mice exposed to 6 Gy or 8 Gy of a 60Co source of γ-rays for total body irradiation (TBI). Survival outcomes were assessed following exposure to 8 Gy or 6 Gy TBI, and hematopoietic damage and intestinal injury were assessed after exposure to 6 Gy TBI. Metformin prolonged the survival of mice exposed to 8 Gy TBI and improved the survival rate of mice exposed to 6 Gy TBI only when administered before exposure to irradiation. Moreover, pretreatment with metformin reduced the frequency of micronuclei (MN) in the bone marrow of mice exposed to 6 Gy TBI. Pretreatment of metformin also protected the intestinal morphology of mice, reduced inflammatory response and decreased the number of apoptotic cells in intestine. In conclusion, we demonstrated that pretreatment with metformin could alleviate irradiation injury.

To assess the effects of exposure to extremely low-frequency magnetic fields (ELF-MFs) on MDCK cell lines, experiments were performed in a chamber under controlled conditions (temperature, humidity and CO2). Therefore, the measured physicochemical and electrical changes in the cells are due solely to the magnetic field exposure and not to external factors. A developed sinusoidal magnetic field generator produced the ELF-MFs with a uniform magnetic field and adjustable intensity and frequency. Three experimental indicators were used: (i) transepithelial electrical impedance (TEEI); (ii) cell migration and proliferation; and (iii) expression of the proteins of the tight junctions, and changes in the area and shape of the cell nuclei. No significant effects on TEEI values were observed when 10 and 50 G 60 Hz magnetic fields were applied to confluent cell monolayers. There were no significant differences in migration and proliferation of the cell monolayer exposed to 60 Hz magnetic fields10 and 50 G , but a contact inhibition factor was observed. The expression of the CLDN-1 protein decreased by 90% compared with the control, while ZO-1 protein expression increased by 120%. No significant effects were observed in the area and shape of the cell nuclei. Experimentation in a controlled environment, under physiological conditions, ensures that the observed effects were strictly due to exposure to magnetic fields. Different exposure conditions are necessary to determine the impact on TEEI and cell migration–proliferation indicators.

Radon inhalation activates antioxidative functions in mouse organs, thereby contributing to inhibition of oxidative stress-induced damage. However, the specific redox state of each organ after radon inhalation has not been reported. Therefore, in this study, we evaluated the redox state of various organs in mice following radon inhalation at concentrations of 2 or 20 kBq/m3 for 1, 3 or 10 days. Scatter plots were used to evaluate the relationship between antioxidative function and oxidative stress by principal component analysis (PCA) of data from control mice subjected to sham inhalation. The results of principal component (PC) 1 showed that the liver and kidney had high antioxidant capacity; the results of PC2 showed that the brain, pancreas and stomach had low antioxidant capacities and low lipid peroxide (LPO) content, whereas the lungs, heart, small intestine and large intestine had high LPO content but low antioxidant capacities. Furthermore, using the PCA of each obtained cluster, we observed altered correlation coefficients related to glutathione, hydrogen peroxide and LPO for all groups following radon inhalation. Correlation coefficients related to superoxide dismutase in organs with a low antioxidant capacity were also changed. These findings suggested that radon inhalation could alter the redox state in organs; however, its characteristics were dependent on the total antioxidant capacity of the organs as well as the radon concentration and inhalation time. The insights obtained from this study could be useful for developing therapeutic strategies targeting individual organs.

The purpose of this study was to use a murine model to determine if melatonin can protect the inner ear from radiation-induced damage. A total of 81 4-week-old Balb/c mice were randomly divided into five groups: control group; 50 mg/kg melatonin group; 5 mg/kg melatonin+radiotherapy group; 50 mg/kg melatonin+radiotherapy group; radiotherapy group. The radiotherapy groups received 16 Gy irradiation and melatonin was administered by intraperitoneal injection 30 min before radiotherapy. On days 3 and 7 after irradiation the function of outer hair cells was determined by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) testing, pathological changes of inner ear cells were observed by light microscopy, and the expression of prestin mRNA was determined. ABR thresholds were increased and wave I latencies were extended after radiotherapy; however, the increases were lower in the groups that received melatonin (P

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.

Unirradiated liver volume (ULV) preservation rate is an important factor associated with radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) undergoing proton beam therapy (PBT). The purpose of this study is to identify the predictors for ULV preservation and quantify the capacity of proton beams in normal liver sparing during PBT. We reviewed planning data of 92 patients with single intrahepatic HCC tumors undergoing PBT. The potential clinical and planning factors that may affect ULV preservation were involved in multiple linear regression for ULV preservation rate. The significant factors were determined to be predictors and their influences were quantified. The median ULV preservation rate was 62.08%. All the assessed clinical factors showed significant effects on ULV preservation rate: clinical target volume (CTV), P

The purpose of this study was to describe the results of definitive radiotherapy (RT) with concurrent chemotherapy for maxillary sinus carcinomas (MSCs) with neck lymph node metastasis to clarify its limitation. Local control (LC), progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan–Meier method and were compared between subgroups using the log rank test. Toxicity was classified using common terminology criteria of adverse events version 5.0. Eighteen patients with inoperable MSC with neck lymph node metastasis including 12 men and 6 women with a median age of 67 years were analyzed. The histologic diagnoses were as follows: 16 patients had squamous cell carcinomas and 2 had other histology. Four patients had stage T3 MSC, 6 had T4a and 8 had T4b. Among 18 patients, 7 received concurrent systemic chemotherapy and 11 received selective arterial chemo-infusion. The median follow-up period was 17 months. The 2-year LC, PFS and OS rates for the entire cohort were 34, 31 and 46%, respectively. No significant differences were observed for LC, PFS and OS rates between systemic chemotherapy and selective arterial chemo-infusion cohorts. Grade 3 or higher acute toxicity, including both non-hematological and hematological, was observed in nine patients (50%), while no grade 3 or higher late toxicity was observed. In conclusion, we described the results of definitive RT for MSCs with neck lymph node metastasis. Local recurrence of primary tumor was a frequent pattern of failure and it should be addressed in future study.

The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced. This phenomenon is known as ‘the dose-rate effect’. The dose-rate effect is considered to be due to the repair of DNA damage during irradiation but the precise mechanisms for the dose-rate effect remain to be clarified. Ku70, Ku86 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are thought to comprise the sensor for DNA double-strand break (DSB) repair through non-homologous end joining (NHEJ). In this study, we measured the clonogenic ability of Ku70-, Ku86- or DNA-PKcs-deficient rodent cells, in parallel with respective control cells, in response to high dose-rate (HDR) and low dose-rate (LDR) γ-ray radiation (~0.9 and ~1 mGy/min, respectively). Control cells and murine embryonic fibroblasts (MEF) from a severe combined immunodeficiency (scid) mouse, which is DNA-PKcs-deficient, showed higher cell survival after LDR irradiation than after HDR irradiation at the same dose. On the other hand, MEF from Ku70−/− mice exhibited lower clonogenic cell survival after LDR irradiation than after HDR irradiation. XR-V15B and xrs-5 cells, which are Ku86-deficient, exhibited mostly identical clonogenic cell survival after LDR and HDR irradiation. Thus, the dose-rate effect in terms of clonogenic cell survival is diminished or even inversed in Ku-deficient rodent cells. These observations indicate the involvement of Ku in the dose-rate effect.

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P

Since the Fukushima Dai-ichi Nuclear Power Plant (F1-NPP) accident in 2011, radiation effects on wildlife in the contaminated areas have been a major concern. The outskirts of the F1-NPP are mainly rural areas, where many rice fields, streams and reservoirs are located. We searched for wild medaka (small aquarium fish) around the F1-NPP and found two wild medaka habitats (S1 and S2). S1 is a stream located 4 km from the F1-NPP, where the ambient dose equivalent rate was 0.4–0.9 μSv/h (2013–14), and S2 is a reservoir located 7.5 km from the F1-NPP, where the ambient dose equivalent rate was 9.8–22 μSv/h (2013–14 and 2017–18). Dosimeters were placed for one day at the locations where the medaka were captured, and the absorbed dose rates were estimated. Radiation effects on wild medaka were examined using micronucleus assay between 2013 and 2018. No significant difference in frequency of micronucleated gill cells was observed among the wild medaka from S1, S2 and our cultivated medaka that were used as a control.

We compared predictive performance between dose volume histogram (DVH) parameter addition and deformable image registration (DIR) addition for gastrointestinal (GI) toxicity in cervical cancer patients. A total of 59 patients receiving brachytherapy and external beam radiotherapy were analyzed retrospectively. The accumulative dose was calculated by three methods: conventional DVH parameter addition, full DIR addition and partial DIR addition. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${D}_{2{cm}^3}$\end{document}, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${D}_{1{cm}^3}$\end{document} and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${D}_{0.1{cm}^3}$\end{document} (minimum doses to the most exposed 2 cm3, 1cm3 and 0.1 cm3 of tissue, respectively) of the rectum and sigmoid were calculated by each method. V50, V60 and V70 Gy (volume irradiated over 50, 60 and 70 Gy, respectively) were calculated in full DIR addition. The DVH parameters were compared between toxicity (≥grade1) and non-toxicity groups. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves were compared to evaluate the predictive performance of each method. The differences between toxicity and non-toxicity groups in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${D}_{2{cm}^3}$\end{document} were 0.2, 5.7 and 3.1 Gy for the DVH parameter addition, full DIR addition and partial DIR addition, respectively. The AUCs of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${D}_{2{cm}^3}$\end{document} were 0.51, 0.67 and 0.57 for DVH parameter addition, full DIR addition and partial DIR addition, respectively. In full DIR addition, the difference in dose between toxicity and non-toxicity was the largest and AUC was the highest. AUCs of V50, V60 and V70 Gy were 0.51, 0.63 and 0.62, respectively, and V60 and V70 were high values close to the value of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${D}_{2{cm}^3}$\end{document} of the full DIR addition. Our results suggested that the full DIR addition may have the potential to predict toxicity more accurately than the conventional DVH parameter addition, and that it could be more effective to accumulate to all pelvic irradiation by DIR.

Institutional imaging protocols for the verification of brachytherapy applicator placements were investigated in a survey study of domestic radiotherapy institutions. The survey form designed by a free on-line survey system was distributed via the mailing-list system of the Japanese Society for Radiation Oncology. Survey data of 75 institutions between August 2019 and October 2019 were collected. The imaging modalities used were dependent on resources available to the institutions. The displacement of a brachytherapy applicator results in significant dosimetric impact. It is essential to verify applicator placements using imaging modalities before treatment. Various imaging modalities used in institutions included a computed tomography (CT) scanner, an angiography X-ray system, a multi-purpose X-ray system and a radiotherapy simulator. The median total exposure time in overall treatment sessions was \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\le$\end{document}75 s for gynecological and prostate cancers. Some institutions used fluoroscopy to monitor the brachytherapy source movement. Institutional countermeasures for reducing unwanted imaging dose included minimizing the image area, changing the imaging orientation, reducing the imaging frequency and optimizing the imaging conditions. It is worth noting that half of the institutions did not confirm imaging dose regularly. This study reported on the usage of imaging modalities for brachytherapy in Japan. More caution should be applied with interstitial brachytherapy with many catheters that can lead to potentially substantial increments in imaging doses for monitoring the actual brachytherapy source using fluoroscopy. It is necessary to share imaging techniques, standardize imaging protocols and quality assurance/quality control among institutions, and imaging dose guidelines for optimization of imaging doses delivered in radiotherapy should be developed.

The aim of the study was to evaluate the risk and threshold doses of lens opacity among residents exposed to low-dose radiation. Residents aged ≥45 years were recruited from a high natural background radiation (HNBR) area in Yangjiang City and a control area selected from nearby Enping City. Lens opacities (LOPs) were classified according to the Lens Opacities Classification System (LOCS) III system. Face-to-face interviews were conducted to collect information on lifestyles, migration and medical history. Life-time cumulative doses were estimated using gender, age, occupancy factors and environmental radiation doses received indoors and outdoors. Logistic regression analyses were conducted to estimate the dose response and determine thresholds. In the HNBR area, among 479 study participants, 101 (21.1%), 245(51.1%) and 23 cases (4.8%), respectively, of cortical, nuclear and posterior subcapsular (PSC) LOPs were found. In the control area, those types of LOPs were identified among 58 cases (12.6%), 206 cases (51.2%) and 6 cases (1.3%) of 462 examinees, respectively. Cumulative eye lens dose was estimated to be 189.5 ± 36.5 mGy in the HNBR area. Logistic analyses gave odds ratios at 100 mGy of 1.26 [95% confidence interval (CI) 1.00–1.60], 0.81 (95% CI 0.64–1.01) and 1.73 (95% CI 1.05–2.85) for cortical, nuclear and PSC LOPs, respectively. For cortical LOPs, a logistic analysis with a threshold dose gave a threshold estimate of 140 mGy (90% CI 110–160 mGy). The results indicated that population exposed to life-time, low-dose-rate environmental radiation was at an elevated risk of cortical and PSC LOPs. A statistically significant threshold dose was obtained for cortical LOPs and no threshold dose for PSC LOPs.

We retrospectively investigated the efficacy and safety of stereotactic body radiotherapy (SBRT) for T1N0M0 lung cancer using CyberKnife (CK) among 13 patients with severe pulmonary dysfunction which was defined as forced expiratory volume in 1 s (FEV1.0) of

This study is a subset analysis of a retrospective multicenter study performed in Japan and its purpose was to investigate the effectiveness of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases from colorectal cancer. Local control (LC), freedom from further metastases, relapse-free survival and overall survival (OS) after SBRT were retrospectively analyzed. The Kaplan–Meier method was used to estimate lifetime data and the log-rank test was performed as univariate analyses. The Cox proportional hazards model was applied in multivariate analyses. Data for 330 patients with 371 tumors were used for analyses. The median follow-up period was 25.0 months. The 3-year LC, freedom from further metastases, relapse-free survival and OS rates were 64.9, 34.9, 24.9 and 63.4%, respectively. The results of multivariate analyses showed that a higher LC rate was associated with no history of local therapy for oligometastases (P = 0.01), SBRT without concurrent chemotherapy (P

In recent years there has been increasing advocacy for highly immunogenic gamma-irradiated vaccines, several of which are currently in clinical or pre-clinical trials. Importantly, various methods of mathematical modelling and sterility testing are employed to ensure sterility. However, these methods are designed for materials with a low bioburden, such as food and pharmaceuticals. Consequently, current methods may not be reliable or applicable to estimate the irradiation dose required to sterilize microbiological preparations for vaccine purposes, where bioburden is deliberately high. In this study we investigated the applicability of current methods to calculate the sterilizing doses for different microbes. We generated inactivation curves that demonstrate single-hit and multiple-hit kinetics under different irradiation temperatures for high-titre preparations of pathogens with different genomic structures. Our data demonstrate that inactivation of viruses such as Influenza A virus, Zika virus, Semliki Forest virus and Newcastle Disease virus show single-hit kinetics following exposure to gamma-irradiation. In contrast, rotavirus inactivation shows multiple-hit kinetics and the sterilizing dose could not be calculated using current mathematical methods. Similarly, Streptococcus pneumoniae demonstrates multiple-hit kinetics. These variations in killing curves reveal an important gap in current mathematical formulae to determine sterility assurance levels. Here we propose a simple method to calculate the irradiation dose required for a single log10 reduction in bioburden (D10) value and sterilizing doses, incorporating both single- and multiple-hit kinetics, and taking into account the possible existence of a resistance shoulder for some pathogens following exposure to gamma-irradiation.

The Japan Clinical Oncology Group–Radiation Therapy Study Group (JCOG-RTSG) has initiated several multicenter clinical trials for high-precision radiotherapy, which are presently ongoing. When conducting multi-center clinical trials, a large difference in physical quantities, such as the absolute doses to the target and the organ at risk, as well as the irradiation localization accuracy, affects the treatment outcome. Therefore, the differences in the various physical quantities used in different institutions must be within an acceptable range for conducting multicenter clinical trials, and this must be verified with medical physics consideration. In 2011, Japan’s first Medical Physics Working Group (MPWG) in the JCOG-RTSG was established to perform this medical-physics-related verification for multicenter clinical trials. We have developed an auditing method to verify the accuracy of the absolute dose and the irradiation localization. Subsequently, we credentialed the participating institutions in the JCOG multicenter clinical trials that were using stereotactic body radiotherapy (SBRT) for lungs, intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for several disease sites, and proton beam therapy (PT) for the liver. From the verification results, accuracies of the absolute dose and the irradiation localization among the participating institutions of the multicenter clinical trial were assured, and the JCOG clinical trials could be initiated.

Radiation therapy is an important method in tumor treatment with distinct responses. This study aimed to investigate the immune effects of radiation therapy on the syngeneic gastric tumor model. Mouse forestomach carcinoma (MFC) cells were irradiated with different X-ray doses. Cell proliferation was determined by clonogenic assay. Gene and protein expression were determined by real-time quantitative PCR and western blot, respectively. The tumor model was established by subcutaneously injecting tumor cells in 615-(H-2 K) mice. Levels of immune-related factors in tumor tissues were determined by immunohistochemistry and flow cytometry. 5 Gy × 3 (three subfractions with 4 h interval) treatment significantly inhibited cell proliferation. Protein expression of stimulator of interferon genes (Sting) and gene expression of IFNB1, TNFα as well as CXCL-9 significantly increased in MFC cells after irradiation. In the MFC mouse model, no obvious tumor regression was observed after irradiation treatment. Further studies showed Sting protein expression, infiltration of dendritic cells and T cells, and significantly increased PD-1/PD-L1 expression in tumor tissues. Moreover, the irradiation treatment activated T cells and enhanced the therapeutic effects of anti-PD1 antibody against MFC tumor. Our data demonstrated that although the MFC tumor was not sensitive to radiation therapy, the tumor microenvironment could be primed after irradiation. Radiation therapy combined with immunotherapy can greatly improve anti-tumor activities in radiation therapy-insensitive tumor models.

This study was aimed at assessing the feasibility and toxicity of using stereotactic body radiation therapy (SBRT) for reirradiation of spinal metastatic tumors. We conducted a retrospective review, from our institutional database, of the data of patients who received reirradiation, with overlap of some prescribed isodose lines to the vertebra from the initial radiation therapy, between 2007 and 2019. We identified 40 patients with spinal metastatic tumors, of whom 2 had 2 metastatic vertebral lesions each, totaling up to 42 target lesions. The median dose to spinal cord at the initial radiation therapy was 30 Gy. SBRT based on the intensity-modulated radiation therapy (IMRT) technique was used for reirradiation to spare the spinal cord. All patients received a prescription dose of 25 Gy in 5 fractions to the planning target volume (PTV). Among the 40 cases who had pain, pain relief was obtained in 24 (60%) after reirradiation. Neurologic improvement was obtained in 8 of 15 cases (53%). The adverse events were evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Reirradiation was well-tolerated, with only 2 patients experiencing adverse events ≥grade 2 in severity, including 1 patient with grade 3 pain, and another patient with grade 3 spinal fracture. None of the patients developed radiation myelopathy. Our data demonstrated that reirradiation of spinal metastasis using SBRT provided effective pain relief and neurologic improvement, with minimal toxicity.

Targeted alpha therapy (TAT) is a promising tumor therapy that can specifically transport α particle to the vicinity of tumor cells while the normal cells are only slightly irradiated. Mesothelin is a highly promising molecular signature for many types of solid tumors including malignant mesothelioma, pancreatic cancer, ovarian cancer and lung adenocarcinoma etc., while the expression in normal human tissues are limited, thus making mesothelin a promising antigen for TAT. Previously we developed a theoretical model that could predict and optimize in vitro screening of potential TAT drugs. The aim of the study is construction and preclinical evaluation of 211At labeled anti-mesothelin antibodies as potential TAT drugs. Mesothelin expression of two tumor cell lines were confirmed by flow cytometry, and their radiosensitivities were also evaluated. We used two kinds of anti-mesothelin antibodies, ET210–6 and ET210–28, to construct TAT drugs. Then, radiochemical purity, stability in vitro, affinity of the conjugates and mesothelin expression level were assessed. The specific killing of mesothelin-positive cancer cells treated by 211At-ET210–28 and 211At-ET210–6 were studied via Cell Counting Kit-8 assay and colony formation assay. 211At-ET210–28 and 211At-ET210–6 revealed excellent affinity and stability in both phosphate buffer saline and fetal bovine serum environment. Radiolabeled antibody conjugates bound specifically to mesothelin-positive cells in vitro. Both 211At-ET210–28 and 211At-ET210–6 could specifically kill mesothelin-positive cells with negligible damages to mesothelin-negative cells. Our findings provide initial proof-of-concept for the potential use of 211At labeled ET210–28/ET210–6 anti-mesothelin antibody in specific killings of mesothelin-positive tumor cells.

Objective To determine the early impact of the COVID-19 pandemic on breast imaging centers in California and Texas and compare regional differences. Methods An 11-item survey was emailed to American College of Radiology accredited breast imaging facilities in California and Texas in August 2020. A question subset addressed March–April government restrictions on elective services (“during the shutdown” and “after reopening”). Comparisons were made between states with chi-square and Fisher’s tests, and timeframes with McNemar’s and paired t-tests. Results There were 54 respondents (54/240, 23%, 26 California, 28 Texas). Imaging volumes fell during the shutdown and remained below pre-pandemic levels after reopening, with reduction in screening greatest (ultrasound 12% of baseline, mammography 13%, MRI 23%), followed by diagnostic MRI (43%), procedures (44%), and diagnostics (45%). California reported higher volumes during the shutdown (procedures, MRI) and after reopening (diagnostics, procedures, MRI) versus Texas (P = 0.001–0.02). Most screened patients (52/54, 96% symptoms and 42/54, 78% temperatures), and 100% (53/53) modified check-in and check-out. Reading rooms or physician work were altered for social distancing (31/54, 57%). Physician mask (45/48, 94%), gown (15/48, 31%), eyewear (22/48, 46%), and face shield (22/48, 46%) use during procedures increased after reopening versus pre-pandemic (P Conclusion Breast imaging volumes during the early pandemic fell more severely in Texas than in California. Safety measures and financial impacts on physicians and staff were similar in both states.

Our aim was to evaluate the efficacy and toxicity of interstitial multicatheter high dose rate brachytherapy (imHDR-BRT) as accelerated partial breast irradiation (APBI) after second breast-conserving surgery (BCS) in patients with ipsilateral breast tumor recurrence (IBTR). Between January 2010 and December 2019, 20 patients with IBTR who refused salvage mastectomy (sMT) were treated with second BCS and post-operative imHDR-BRT as APBI. All patients had undergone primary BCS followed by adjuvant external beam radiotherapy. Median imHDR-BRT dose was 32 Gy delivered in twice-daily fractions of 4 Gy. Five-year IBTR-free survival, distant metastasis-free survival (DMFS), overall survival (OS) as well as toxicity and cosmesis were evaluated in the present retrospective analysis. Median age at recurrence and median time from the first diagnosis to IBTR was 65.1 years and 12.2 years, respectively. After a median follow-up of 69.9 months, two patients developed a second local recurrence resulting in 5-year IBTR free-survival of 86.8%. Five-year DMFS and 5-year OS were 84.6% and 92.3%, respectively. Grade 1–2 fibrosis was noted in 60% of the patients with no grade 3 or higher toxicity. Two (10%) cases of asymptomatic fat necrosis were documented. Cosmetic outcome was classified as excellent in 6 (37.5%), good in 6 (37.5%), fair in 3 (18.75%) and poor in 1 (6.25%) patient, respectively. We conclude that imHDR-BRT as APBI re-irradiation is effective and safe for IBTR and should be considered in appropriately selected patients.

Objective To assess the impact of the COVID-19 pandemic on breast imaging facilities’ operations and recovery efforts across North America. Methods A survey on breast imaging facilities’ operations and strategies for recovery during the COVID-19 pandemic was distributed to the membership of the Society of Breast Imaging and National Consortium of Breast Centers from June 4, 2020, to July 14, 2020. A descriptive summary of responses was performed. Comparisons were made between demographic variables of respondents and questions of interest using a Pearson chi-square test. Results There were 473 survey respondents (response rate of 13%). The majority of respondents (70%; 332/473) reported 80%–100% breast imaging volume reduction, with 94% (447/473) reporting postponement of screening mammography. The majority of respondents (97%; 457/473) continued to perform biopsies. There were regional differences in safety measures taken for staff (P = 0.004), with practices in the West more likely reporting no changes in the work environment compared to other regions. The most common changes to patients’ experience included spacing out of furniture in waiting rooms (94%; 445/473), limiting visitors (91%; 430/473), and spacing out appointments (83%). A significantly higher proportion of practices in the Northeast (95%; 104/109) initiated patient scheduling changes compared to other regions (P = 0.004). Conclusion COVID-19 had an acute impact on breast imaging facilities. Although common national operational patterns emerged, geographic variability was notable in particular in recovery efforts. These findings may inform future best practices for delivering breast imaging care amid the ongoing and geographically shifting COVID-19 pandemic.

The novel SARS-CoV2 (COVID-19) pandemic has had a major impact on breast radiology practices. Initially, nonessential imaging studies, including screening mammography, were curtailed and even temporarily halted when lockdowns were instituted in many parts of the United States. As a result, imaging volumes plummeted while health care institutions worked to ensure safety measures were in place to protect patients and personnel. As COVID-19 infection levels started to stabilize in some areas, breast radiology practices sought guidance from national organizations, such as the Centers for Disease Control and Prevention, the Centers for Medicare and Medicaid Services, and radiology specialty societies, to develop strategies for patients to safely return for screening mammograms and other outpatient imaging studies. Postponement of breast cancer screening has led to delays in cancer diagnosis and treatment that could negatively affect patient outcomes for years to come. In order to continue to provide necessary imaging services, breast radiologists will need to face and overcome ongoing practical challenges related to the pandemic, such as negative financial impacts on practices and patients, the need for modifications in delivery of imaging services and trainee education, and differences in the health care system as a whole, including the shift to telehealth for clinical care. Nonetheless, despite the disruption the COVID-19 pandemic has caused, the need for breast radiology procedures, including breast cancer screening, remains strong.

Small cell lung cancer (SCLC) has been a devastating actuality in clinic and the molecular mechanisms underlying this disease remain unclear. The epigenetic alterations located in the promoter region of human telomerase reverse transcriptase (hTERT) have been demonstrated as one of the most prevalent non-coding genomic modifications in multiple cancers. However, alteration of hTERT promoter methylation in SCLC and the subsequently induced change in tumor cell behavior remains unclear. In this research, we hypothesized that abnormal methylation of hTERT promotor enhanced the progression of SCLC and the outcome of radiotherapy resistance. Quantitative real-time PCR and western blot assays were performed to evaluate the RNA and protein levels of hTERT and enhancer of zeste homolog 2 (EZH2), respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to estimate the viability and X-ray sensitivity of H20 and H446 cell lines. Functionally, upregulation of hTERT promoted the proliferation and migration of H20 and H446 cells, and the high-level of methylation in the promoter region of hTERT induced by radiation caused radio-resistance in SCLC. Mechanically, methylation of hTERT promoter enhanced the progression and radio-resistance of SCLC through upregulating the expression of its downstream effector EZH2.