A Breakthrough on Modeling Cancer Prevention and Elimination by Low Radiation Doses.

Background: We are exposed to natural ionizing radiation and other genomic stressors throughout life and radiophobia has caused much harm to society. The main basis for radiophobia is the invalid linear no-threshold (LNT) hypothesis for cancer induction, which the System of Radiological Protection (SRP) is linked to. Largely unknown to the public, evolution-associated genomic stress adaptation (gensadaptation) over many previous generations now provides protection to all lifeforms from low radiation doses. Objective: To help bring about an improved SRP not linked to the invalid LNT hypothesis for radiation-caused health detriment and to promote low-dose radiation therapy for different diseases. Methods: All-solid-cancer mortality risk dose-response relationships for A-bomb survivors were generated based on published LNT-modeling-related results. Dose-response relationships for lung cancer prevention by low-dose radiation were generated by linear interpolation based on published data from a study using > 15,000 mice. Uncertainty characterization was based on Monte Carlo calculations for binomial and Poisson distributions. New dose characterization tools were used for threshold dose-response relationships for radiation-caused cancer mortality. Results: The all-solid-cancer mortality risk for A-bomb survivors transitioned from LNT to threshold-linear when adjusted for key missing uncertainty at low doses. The prevention of lung cancer in mice by low radiation doses depends on the radiation absorbed dose and type. Conclusions: The SRP should be linked to population dose thresholds rather than the invalid LNT hypothesis and small likely harmless radiation doses could possibly be used in treating different diseases.

102 Background: In treating esophageal cancer chemo-radiation is used in the definitive as well as neo-adjuvant setting. Optimal dosage of radiation for best outcome has been debated. The aim of this study is to evaluate clinical outcomes of lower radiation dosage compared to higher. Methods: Online search for studies comparing radiation dose from 1990 to present was performed. Primary outcome was overall-survival rates for up to 5 years. Secondary outcomes included post-treatment complications and treatment response. A cut point of 51 Gy and less was considered as lower dose and greater than 51 Gy was considered higher dose. Quality of included studies was evaluated by STROBE criteria. Relative Risk (RR) and 95% Confidence Intervals (CI) were calculated from pooled data. Results: The search strategy yielded 142 studies, 12 met our selection criteria and included 1876 patients receiving radiation for resectable esophageal carcinoma. Of these patients, 1057 received lower and 819 were treated with greater than 51 Gy. Median age was 63 and 64 years for lower and higher radiation dose respectively. Meta-analysis showed no statistically significant difference in survival and toxicities between the two groups. 1 year overall survival (RR = 0.97, 95% CI 0.84-1.13, p = 0.69), 2 year overall survival (RR = 1.29, 95% CI 0.76-2.19, p = 0.34), 3 year overall survival (RR = 1.18, 95% CI 0.83-1.68, p = 0.37), 4 year overall survival (RR = 1.37, 95% CI 0.64-2.94, p = 0.41), 5 year overall survival (RR = 1.11, 95% CI 0.72-1.69, p = 0.64), Esophagitis (RR = 0.76, 95% CI 0.39-1.50, p = 0.43), Dermatitis (RR = 0.98, 95% CI 0.12-7.94, p = 0.99), Fistula formation (RR = 0.72, 95% CI 0.32-1.60, p = 0.42), Hematologic complications (RR = 1.10, 95% CI 0.20-6.02, p = 0.91), Stricture formation (RR = 1.39, 95% CI 0.54-3.58, p = 0.5). Conclusions: Lower radiation dose appears to be as effective as higher dose in esophageal carcinoma with similar toxicity profile and survival rates. Larger prospective randomized trials, focusing on patient-reported quality-of-life are required to consolidate these results.

A conference on Bridging Radiation Policy and Science took place at Warrenton, VA, USA on 1-5 December 1999. Some 70 invited delegates met in the plantation-style manorial surroundings of Airlie House to continue the discussion of how to set policy for radiation protection against a background of scientific discussion on the effects of low radiation doses. The meeting was a follow-up to the `Wingspread Conference' in Racine, Washington in 1977. The sponsors of the conference were the International Nuclear Energy Academy, International Nuclear law Association, International Nuclear Societies Council, International Radiation Protection Association and the World Federation of Nuclear Medicine and Biology. The conference was chaired by Gail de Planque and the programme committee by Sigurdur Magnusson from Iceland. The meeting was organised by Burk & Associates on behalf of the US Health Physics Society. Although there was a strong US presence, the organisers and, in particular, the programme committee had gone to great lengths to ensure participation from the international community and a broad range of interests. The participants came from organisations as diverse in their views as (in no particular order) USNRC, USEPA, Greenpeace, ICRP, The House of Commons, JAERE, ANSTO, Friends of the Earth, BNFL, IAEA, IPSN, The French Academy of Sciences and the World Council of Nuclear Workers.

Practical Strategies to Reduce Pediatric CT Radiation Dose

Radioactive response in primary mouse spermatocytes revealed by analysis of synaptonemal complexes

The radioprotective agent amifostine is a free radical scavenger that can protect cells from the damaging effects of ionising radiation when administered prior to radiation exposure. However, amifostine has also been shown to protect cells from chromosomal mutations when administered after radiation exposure. As apoptosis is a common mechanism by which cells with mutations are removed from the cell population, we investigated whether amifostine stimulates apoptosis when administered after radiation exposure. We chose to study a relatively low dose which is the maximum radiation dose for radiation emergency workers (0.25 Gy) and a high dose relevant to radiotherapy exposures (6 Gy). Mice were administered 400 mg/kg amifostine 30 min before, or 3 h after, whole-body irradiation with 0.25 or 6 Gy X-rays and apoptosis was analysed 3 or 7 h later in spleen and bone marrow. We observed a significant increase in radiation-induced apoptosis in the spleen of mice when amifostine was administered before or after 0.25 Gy X-rays. In contrast, when a high dose of radiation was used (6 Gy), amifostine caused a reduction in radiation-induced apoptosis 3 h post-irradiation in spleen and bone marrow similar to previously published studies. This is the first study to investigate the effect of amifostine on radiation-induced apoptosis at a relatively low radiation dose and the first to demonstrate that while amifostine can reduce apoptosis from high doses of radiation, it does not mediate the same effect in response to low-dose exposures. These results suggest that there may be a dose threshold at which amifostine protects from radiation-induced apoptosis and highlight the importance of examining a range of radiation doses and timepoints.

Non-cancer diseases and non-targeted effects

Purpose: Radiation dose used in the neoadjuvant chemoradiotherapy (NCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) varies in different trials and clinical practice.Methods and Materials: Data from patients diagnosed with ESCC receiving NCRT followed by esophagectomy were retrospectively collected from February 2013 to December 2017. Lower dose (LD) radiotherapy was defined as ≤45 Gy, and >45 Gy was considered as higher dose (HD). Survival rates were calculated by the Kaplan–Meier method and compared with long-rank test. Multivariate Cox regression analyses were performed to identify variables associated with survival.Results: A total of 118 patients treated with NCRT were included in our analysis: 62 patients received LD radiotherapy, and 56 patients received HD radiotherapy. The median follow-up time was 24.3 months (0.67–65.3 m). Two-years overall survival (OS) rates were 75.0 and 79.0% in HD and LD group, respectively (P = 0.360), and complete pathological remission (pCR) rates in two groups were 42.9 and 30.6%, respectively (P = 0.17). The incidences of toxic effects including post-operative complications were not significantly different between two groups. Multivariate analysis showed that tumor T stage, M1a disease, smoking history, and pCR rate were significantly associated with OS.Conclusions: In ESCC patients treated with NCRT followed by surgery, higher radiation dose was not significantly associated with a higher pCR rate and longer survival. Lower radiation dose might be a preferable time-dose fraction scheme. Our finding needs to be further validated by randomized trials.

IAEA/WHO International Conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, Seville, Spain, 17-21 November 1997 (IAEA-CN-67)

Historically, biology has not been subjected to any epistemological analysis as has been the case with mathematics and physics. Our knowledge of the effects in biological systems of various stimuli proves to be dualistic in a complementary (although not mutually exclusive) way, which bears resemblance to the knowledge of phenomena in quantum physics. The dualistic "limbs" of biological knowledge are the action of stimuli and the response of the exposed, biological system. With regard to radiogenic cancer, this corresponds to the action of the ionizations and the response of the exposed mammal to that action, respectively. The following conclusions can be drawn from the present analysis: Predictions as to radiogenic cancer seem often if not always to have neglected the response variability (variations in radiosensitivity) in individuals or among individuals in populations, i.e. the predictions have been based exclusively on radiation doses and exposure conditions. The exposed individual or population, however, must be considered an "open statistical system", i.e. a system in which predictions as to the effect of an agent are only conditionally possible. The knowledge is inverse to the size of the dose or concentration of the active agent. On epistemological grounds, we can not gain knowledge about the carcinogenic capacity of very low (non-dominant) radiation doses. Based on the same principle, we can not predict cancer risks at very low (non-dominant) radiation doses merely on the basis of models, or otherwise interpolated or extrapolated high-dose effects, observed under special exposure conditions.

BackgroundDynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is a functional imaging modality that can quantify tissue permeability and blood flow. Due to vasculature changes resulting from radiation therapy (RT), DCE-MRI quantitative parameters should be significantly different in regions receiving a high radiation dose compared to regions receiving a low radiation dose. This work sought to determine if a significant difference exists in post head and neck cancer (HNC)-RT DCE-MRI quantitative parameters Ktransand vebetween regions of the mandible receiving a high radiation dose and regions of the mandible receiving a low radiation dose.MethodsDCE-MRI was acquired from HNC subjects post-RT. The DCE-MRI quantitative parameters Ktransand vewere obtained through Tofts model fitting. Four mandible sections (left ramus, left body, right ramus, and right body) were delineated on subject mandible contours. Two Kruskal-Wallis tests comparing the mean Ktransand vein low dose (≤ 60 Gy) areas of the four mandible regions were computed. Next, two Wilcoxon signed-rank tests were used to determine if the means of Ktransand vebetween high dose (> 60 Gy) and low dose (≤ 60 Gy) mandible regions were significantly different. To account for multiple statistical tests, a Bonferroni corrected significance level for all statistical tests was used.Results48 HNC subjects were included in the analysis. The Kruskal-Wallis tests showed no inherent significant difference in Ktransmeans between mandible regionsand no inherent significant difference in vemeans between mandible regions. No significant difference was found between high and low dose Ktransmandible means (W=392,p=0.044). A significant difference was found between high and low dose vemandible means (W=214,p=0.00013).ConclusionsNo inherent difference in DCE-MRI quantitative parameters was observed within subject mandibles, but a significant difference was observed between vemeans of high and low radiation dose mandible regions. These results provide evidence of the utility of DCE-MRI to monitor mandible vasculature changes resulting from head and neck cancer radiation therapy. Monitoring post HNC-RT mandible vasculature changes is important to initiate earlier toxicity management and ultimately improve HNC survivor quality of life.Simple SummaryDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can detect relative differences in anatomical blood perfusion and vessel permeability. Differences in vascularity should occur between mandible regions receiving a large radiation dose and regions receiving a low radiation dose during head and neck cancer radiation therapy. In this study, we determined if DCE-MRI can be used to detect vasculature differences between mandible regions irradiated with high and low amounts of radiation. The results indicate that one of the DCE-MRI parameters was significantly different between irradiated mandible regions receiving high and low radiation dose. This parameter may be used as an early marker for mandible radiation damage from head and neck radiation therapy.

The system of radiological protection has been based on linear no-threshold theory and related dose-response models for health detriment (in part related to cancer induction) by ionizing radiation exposure for almost 70 y. The indicated system unintentionally promotes radiation phobia, which has harmed many in relationship to the Fukushima nuclear accident evacuations and led to some abortions following the Chernobyl nuclear accident. Linear no-threshold model users (mainly epidemiologists) imply that they can reliably assess the cancer excess relative risk (likely none) associated with tens or hundreds of nanogray (nGy) radiation doses to an organ (e.g., bone marrow); for 1,000 nGy, the excess relative risk is 1,000 times larger than that for 1 nGy. They are currently permitted this unscientific view (ignoring evolution-related natural defenses) because of the misinforming procedures used in data analyses of which many radiation experts are not aware. One such procedure is the intentional and unscientific vanishing of the excess relative risk uncertainty as radiation dose decreases toward assigned dose zero (for natural background radiation exposure). The main focus of this forum article is on correcting the serious error of discarding risk uncertainty and the impact of the correction. The result is that the last defense of the current system of radiological protection relying on linear no-threshold theory (i.e., epidemiologic studies implied findings of harm from very low doses) goes away. A revised system is therefore needed.

Prodiginines are bacterial red polypyrrole pigments and multifaceted secondary metabolites. These agents have anti-proliferative, immunosuppressive, antimicrobial, and anticancer effects. Recent analysis revealed that prodigiosin hypersensitizes Serratia marcescens to gamma radiation. In the present study, we report the cytotoxicity and genotoxicity properties of undecylprodigiosin and butylcycloheptylprodigiosin in the presence and absence of radiation through the MTT and alkaline comet experiments. Findings demonstrated that undecylprodigiosin was at least a fivefold more cytotoxic at low radiation doses (1 and 3Gy) on both MCF7 and HDF lines rather than in the absence or high radiation doses (5Gy) (P value < 0.05). Although butylcycloheptylprodigiosin toxicity on MCF7 and HDF was dose-dependent, it was not influenced by any radiation doses (P value > 0.05). Comet findings confirmed that these compounds' genotoxicity is only dose-dependent. Radiation had no significant effects on DNA damage on any of the cells (P value > 0.05). In general, it can be concluded that the prodiginines are cytotoxic agents that act as a double-edged sword, radiosensitizers and radio-protective, respectively at low and high radiation doses in cancer treatment process. As the results they could be used in antitumor therapies very soon.

Radiation Management for Interventions Using Fluoroscopic or Computed Tomographic Guidance during Pregnancy: A Joint Guideline of the Society of Interventional Radiology and the Cardiovascular and Interventional Radiological Society of Europe with Endorsement by the Canadian Interventional Radiology Association

In current computed tomography (CT) architecture, both X-ray tubes and X-ray detectors are rotated mechanically around an object to collect a sufficient number of projections. This architecture has been shown to not be fast enough for patients with high or irregular heart rates. Furthermore, both X-ray beams and detectors of the current architecture are made wide enough, so that the entire object is covered in the lateral direction without data truncation. Although novel acquisition protocols have recently been developed to reduce a radiation exposure, the high radiation dose from CT imaging remains a heightened public concern (especially for cardiac CT). The current CT architecture is a major bottleneck to further increase the temporal resolution and reduce the radiation dose. To overcome these problems, we present an innovative stationary-sources rotating-detectors CT (SSRD-CT) architecture based on the three stationary distributed X-ray sources and three smaller rotating X-ray detectors. Each distributed X-ray source has ~ 100 distinctive X-ray focal spots, and each detector has a narrower width compared with the conventional CT detectors. The SSRD-CT will have a field-of-view of 200 mm in diameter at isocenter, which is large enough to image many internal organs, including hearts. X-rays from the distributed sources are activated electronically to simulate the mechanical spinning of conventional single-beam X-ray sources with a high speed. The activation of individual X-ray beam will be synchronized to the corresponding rotating detector at the opposite end. Three source-detector chains can work in parallel to acquire three projections simultaneously and improve temporal resolution. Lower full-body radiation dose is expected for the proposed SSRD-CT because X-rays are restricted to irradiate a local smaller region. Taken together, the proposed SSRD-CT architecture will enable ≤50-ms temporal resolution and reduce radiation dose significantly.