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\"On March 28, 1979, the worst nuclear reactor accident in U.S. history occurred at the Three Mile Island power plant in Central Pennsylvania. Radiation Nation tells the story of what happened then and in the following months and years, as residents tried to make sense of the emergency. The near-meltdown occurred at a pivotal moment when the New Deal coalition was unraveling, trust in government was eroding, conservatives were consolidating their power, and the political left was becoming marginalized. Using the accident to explore this turning point, Natasha Zaretsky provides a fresh interpretation of the era by disclosing how atomic and ecological imaginaries shaped the conservative ascendancy. Drawing on the testimony of the men and women who lived in the shadow of the reactor, Radiation Nation shows that the region's citizens, especially its mothers, grew convinced that they had sustained radiological injuries that threatened their reproductive futures. Taking inspiration from the antiwar, environmental, and feminist movements, women at Three Mile Island crafted a homegrown ecological politics that wove together concerns over radiological threats to the body, the struggle over abortion and reproductive rights, and eroding trust in authority. This politics was shaped above all by what Zaretsky calls \"biotic nationalism,\" a new body-centered nationalism that imagined the nation as a living, mortal being and portrayed sickened Americans as evidence of betrayal. The first cultural history of the accident, Radiation Nation reveals the surprising ecological dimensions of post-Vietnam conservatism while showing how growing anxieties surrounding bodily illness infused the political realignment of the 1970s in ways that blurred any easy distinction between left and right.\"--Provided by publisher.

A randomized trial showed noninferiority of stereotactic body radiotherapy to conventionally or moderately hypofractionated radiotherapy in preventing biochemical recurrence in selected men with localized prostate cancer.

We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial. FAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1–3, pN0–1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1·6% excess for five-fraction schedules (critical hazard ratio [HR] of 1·81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132. Between Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71·5 months (IQR 71·3 to 71·7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0·86 (95% CI 0·51 to 1·44) for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2·1% (1·4 to 3·1); estimated absolute differences versus 40 Gy in 15 fractions were −0·3% (−1·0 to 0·9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior five-fraction schedule: p=0·0022 vs 40 Gy in 15 fractions) and −0·7% (−1·3 to 0·3) for 26 Gy in five fractions (p=0·00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9·9%) 40 Gy patients, 155 (15·4%) of 1005 27 Gy patients, and 121 of 1020 (11·9%) 26 Gy patients. Across all clinician assessments from 1–5 years, odds ratios versus 40 Gy in 15 fractions were 1·55 (95% CI 1·32 to 1·83, p<0·0001) for 27 Gy in five fractions and 1·12 (0·94 to 1·34, p=0·20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy. 26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer. National Institute for Health Research Health Technology Assessment Programme.

Background Intraglandular therapy with adipose-derived mesenchymal stromal cells (ASCs) for radiation-induced xerostomia and hyposalivation has shown promising effects on the salivary flow rate and in patient-reported outcomes. However, the mode of action is not fully understood, but changes in the salivary proteome have been observed. Methods This sub study, to the randomised, double-blinded, placebo-controlled trial investigating intraglandular mesenchymal stromal cells for radiation-induced hyposalivation (MESRIX-III), examines changes in the salivary proteome following intraglandular therapy into the submandibular glands with allogenic ASCs in unstimulated whole saliva (UWS) in previous head and neck cancer patients with radiation-induced hyposalivation. A total of 120 patients were included and randomised in a 1:1 ratio to receive intraglandular injections with either ASCs or placebo (CryoStor10, 10% dimethyl sulfoxide, Biolife Solutions). UWS samples was collected at baseline and at 4 months post transplantation. The main endpoint is comparison of the salivary human proteome evaluated by mass spectrometry analysis in the group receiving ASCs compared to placebo at 4 months. Secondary outcomes are comparison of the microbial proteome in the group receiving ASCs compared to placebo at 4 months; changes in the salivary proteome and microbial proteome in the group receiving ASCs from baseline to 4 months and evaluation of the salivary proteome and microbial proteome following radiation therapy at baseline in both groups. Discussion This study will gain insights into the potential mode of action of intraglandular ASC therapy for radiation-induced hyposalivation. The results may open avenues for a clinically applicable and disease-modifying treatment to ameliorate hyposalivation and restore salivary gland function following radiation therapy in previous head and neck cancer patients. Moreover, it will constitute the most extensive collection of data characterising the salivary proteome post-radiation therapy in the head and neck region. Trial registration The MESRIX-III study is approved by the Danish Data Protection Agency (protocol number P-2020–1164), the National Ethics Committee (protocol number: 1802872) and the Danish Medical Agency (2018–000348-24) and is registered at the ClinicalTrials.gov database (NCT04776538). First posted on clinicaltrials.gov 03-JAN-2021.

Background Whole brain radiation therapy (WBRT) is the standard therapy for multiple brain metastases. However, WBRT has a poor local tumor control and is associated with a decline in neurocognitive function (NCF). Aim of this trial is to assess the efficacy and safety of a new treatment method, the WBRT with hippocampus avoidance (HA) combined with the simultaneous integrated boost (SIB) on metastases/resection cavities (HA-WBRT+SIB). Methods This is a prospective, randomized, two-arm phase II multicenter trial comparing the impact of HA on NCF after HA-WBRT+SIB versus WBRT+SIB in patients with multiple brain metastases. The study design is double-blinded. One hundred thirty two patients are to be randomized with a 1:1 allocation ratio. Patients between 18 and 80 years old are recruited, with at least 4 brain metastases of solid tumors and at least one, but not exceeding 10 metastases ≥5 mm. Patients must be in good physical condition and have no metastases/resection cavities in or within 7 mm of the hippocampus. Patients with dementia, meningeal disease, cerebral lymphomas, germ cell tumors, or small cell carcinomas are excluded. Previous irradiation and resection of metastases, as well as the number and size of metastases to be boosted have to comply with certain restrictions. Patients are randomized between the two treatment arms: HA-WBRT+SIB and WBRT+SIB. WBRT is to be performed with 30 Gy in 12 daily fractions and the SIB with 51 Gy/42 Gy in 12 daily fractions on 95% of volume for metastases/resection cavities. In the experimental arm, the dose to the hippocampi is restricted to 9 Gy in 98% of the volume and 17Gy in 2% of the volume. NCF testing is scheduled before WBRT, after 3 (primary endpoint), 9, 18 months and yearly thereafter. Clinical and imaging follow-ups are performed 6 and 12 weeks after WBRT, after 3, 9, 18 months and yearly thereafter. Discussion This is a protocol of a randomized phase II trial designed to test a new strategy of WBRT for preventing cognitive decline and increasing tumor control in patients with multiple brain metastases. Trial registration The HIPPORAD trial is registered with the German Clinical Trials Registry ( DRKS00004598 , registered 2 June 2016).

Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients’ quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage.

In 2007, we began the randomised phase 3 multicentre HYPRO trial to investigate the effect of hypofractionated radiotherapy compared with conventionally fractionated radiotherapy on relapse-free survival in patients with prostate cancer. Here, we examine whether patients experience differences in acute gastrointestinal and genitourinary adverse effects. In this randomised non-inferiority phase 3 trial, done in seven radiotherapy centres in the Netherlands, we enrolled intermediate-risk or high-risk patients aged between 44 and 85 years with histologically confirmed stage T1b–T4 NX-0MX-0 prostate cancer, a PSA concentration of 60 ng/mL or lower, and WHO performance status of 0–2. A web-based application was used to randomly assign (1:1) patients to receive either standard fractionation with 39 fractions of 2 Gy in 8 weeks (five fractions per week) or hypofractionation with 19 fractions of 3·4 Gy in 6·5 weeks (three fractions per week). Randomisation was done with minimisation procedure, stratified by treatment centre and risk group. The primary endpoint is 5-year relapse-free survival. Here we report data for the acute toxicity outcomes: the cumulative incidence of grade 2 or worse acute and late genitourinary and gastrointestinal toxicity. Non-inferiority of hypofractionation was tested separately for genitourinary and gastrointestinal acute toxic effects, with a null hypothesis that cumulative incidences of each type of adverse event were not more than 8% higher in the hypofractionation group than in the standard fractionation group. We scored acute genitourinary and gastrointestinal toxic effects according to RTOG-EORTC criteria from both case report forms and patients' self-assessment questionnaires, at baseline, twice during radiotherapy, and 3 months after completion of radiotherapy. Analyses were done in the intention-to-treat population. Patient recruitment has been completed. This study is registered with www.controlled-trials.com, number ISRCTN85138529. Between March 19, 2007, and Dec 3, 2010, 820 patients were randomly assigned to treatment with standard fractionation (n=410) or hypofractionation (n=410). 3 months after radiotherapy, 73 (22%) patients in the standard fractionation group and 75 (23%) patients in the hypofractionation group reported grade 2 or worse genitourinary toxicity; grade 2 or worse gastrointestinal toxicity was noted in 43 (13%) patients in the standard fractionation group and in 42 (13%) in the hypofractionation group. Grade 4 acute genitourinary toxicity was reported for two patients, one (<1%) in each group. No grade 4 acute gastrointestinal toxicities were observed. We noted no significant difference in cumulative incidence by 120 days after radiotherapy of grade 2 or worse acute genitourinary toxicity (57·8% [95% CI 52·9–62·7] in the standard fractionation group vs 60·5% (55·8–65·3) in the hypofractionation group; difference 2·7%, 90% CI −2·99 to 8·48; odds ratio [OR] 1·12, 95% CI 0·84–1·49; p=0·43). The cumulative incidence of grade 2 or worse acute gastrointestinal toxicity by 120 days after radiotherapy was higher in patients given hypofractionation (31·2% [95% CI 26·6–35·8] in the standard fractionation group vs 42·0% [37·2–46·9] in the hypofractionation group; difference 10·8%, 90% CI 5·25–16·43; OR 1·6; p=0·0015; non-inferiority not confirmed). Hypofractionated radiotherapy was not non-inferior to standard fractionated radiotherapy in terms of acute genitourinary and gastrointestinal toxicity for men with intermediate-risk and high-risk prostate cancer. In fact, the cumulative incidence of grade 2 or worse acute gastrointestinal toxicity was significantly higher in patients given hypofractionation than in those given standard fractionated radiotherapy. Patients remain in follow-up for efficacy endpoints. The Dutch Cancer Society.

Radiotherapy is a key foundation of oncologic treatment that is used across the spectrum of cancer indications. Advances in imaging, treatment planning, and dose delivery have led to increasingly conformal and even ablative treatments, which have resulted in improved tumor control with no increase in the risk of side effects (or with a decrease in risk) as compared with previous treatments. These advances have facilitated the combined use of radiotherapy with efficacious systemic therapies, including targeted treatments and immunotherapies. Radiation-induced changes in normal tissue occur as a result of stem-cell senescence, inflammation, vascular changes, fibroblast activation, and loss of parenchymal cells. Research into the biologic underpinnings of radiation-induced changes in normal tissue, biomarkers of side effects of various irradiation regimens, and new treatment methods offers great promise for further increasing the efficacy of radiotherapy and improving the side-effect profile through personalized approaches. This review summarizes advances in radiotherapy that reduce injury to normal tissue, including improvements in the precision of imaging and delivery, and outlines strategies to prevent and manage treatment-related side effects.

The threat of nuclear or radiological events requires early diagnostic tools for radiation induced health effects. Localized radiation injuries (LRI) are severe outcomes of such events, characterized by a latent presymptomatic phase followed by symptom onset ranging from erythema and edema to ulceration and tissue necrosis. Early diagnosis is crucial for effective triage and adapted treatment, potentially through minimally invasive biomarkers including circulating microRNAs (miRNAs), which have been correlated with tissue injuries and radiation exposure, suggesting their potential in diagnosing LRI. In this study, we sought to identify early miRNA signatures for LRI severity prognosis before clinical symptoms appear. Using a mouse model of hindlimb irradiation at 0, 20, 40, or 80 Gy previously shown to lead to localized injuries of different severities, we performed broad-spectrum plasma miRNA profiling at two latency stages (day 1 and 7 post-irradiation). The identified candidate miRNAs were then challenged using two independent mouse cohorts to refine miRNA signatures. Through sparse partial least square discriminant analysis (sPLS-DA), signatures of 14 and 16 plasma miRNAs segregated animals according to dose groups at day 1 and day 7, respectively. Interestingly, these signatures shared 9 miRNAs, including miR-19a-3p, miR-93-5p, miR-140-3p, previously associated with inflammation, radiation response and tissue damage. In addition, the Bayesian latent variable modeling confirmed significant correlations between these prognostic miRNA signatures and day 14 clinical and functional outcomes from unrelated mice. This study identified plasma miRNA signatures that might be used throughout the latency phase for the prognosis of LRI severity. These results suggest miRNA profiling could be a powerful tool for early LRI diagnosis, thereby improving patient management and treatment outcomes in radiological emergency situations.

Purpose Although vaginal dilator use after combined pelvic radiation therapy and brachytherapy (RT/BT) is recommended to prevent vaginal shortening and stenosis, women fail to use them and experience sexual problems. A nurse-led sexual rehabilitation intervention targeting sexual recovery and vaginal dilatation was developed. Its feasibility was investigated during a prospective, longitudinal, observational pilot study. Methods Four oncology nurses were specifically trained to conduct the intervention. Gynecologic cancer patients treated with RT/BT were assessed using (i) questionnaires on frequency of dilator use (monthly), sexual functioning, and sexual distress (at baseline and 1, 6, and 12 months) and psychological and relational distress (at 1, 6, and 12 months); (ii) semi-structured interviews (between 6 and 12 months); and (iii) consultation recordings (a random selection of 21 % of all consults). Results Twenty participants were 26–71 years old (mean = 40). Eight participants discontinued participation after 3 to 9 months. At 6 months after RT, 14 out of 16 (88 %), and at 12 months 9 out of 12 (75 %), participants dilated regularly, either by having sexual intercourse or by using dilators. Sexual functioning improved between 1 and 6 months after RT, with further improvement at 12 months. Most participants reported that the intervention was helpful and the nurses reported having sufficient expertise and counseling skills. Conclusions According to the pilot results, the intervention was feasible and promising for sexual rehabilitation and regular dilator use after RT. Its (cost-)effectiveness will be investigated in a randomized controlled trial.