ALBERT

Description: The REID quantifies the lifetime risk of death from radiation-induced cancer in an exposed astronaut. The NASA Space Cancer Risk (NSCR) 2012 mode incorporates elements from physics, biology, epidemiology, and statistics to generate the REID distribution. The current model quantifies the space radiation environment, radiation quality, and dose-rate effects to estimate a NASA-weighted dose. This weighted dose is mapped to the excess risk of radiation-induced cancer mortality from acute exposures to gamma rays and then transferred to an astronaut population. Finally, the REID is determined by integrating this risk over the individual's lifetime. The calculated upper 95% confidence limit of the REID is used to restrict an astronaut's permissible mission duration (PMD) for a proposed mission. As a statistical quantity characterized by broad, subjective uncertainties, REID estimates for space missions result in wide distributions. Currently, the upper 95% confidence level is over 350% larger than the mean REID value, which can severely limit an astronaut's PMD. The model incorporates inputs from multiple scientific disciplines in the risk estimation process. Physics and particle transport models calculate how radiation moves through space, penetrates spacecraft, and makes its way to the human beings onboard. Epidemiological studies of exposures from atomic bombings, medical treatments, and power plants are used to quantify health risks from acute and chronic low linear energy transfer (LET) ionizing radiation. Biological studies in cellular and animal models using radiation at various LETs and energies inform quality metrics for ions present in space radiation. Statistical methodologies unite these elements, controlling for mathematical and scientific uncertainty and variability. Despite current progress, these research platforms contain knowledge gaps contributing to the large uncertainties still present in the model. The NASA Space Radiation Program Element (SRPE) defines the knowledge gaps that impact our understanding of the cancer risks. These gaps are outlined in NASA's Human Research Roadmap [4], which identifies the research questions and actions recommended for reducing the uncertainty in the current NSCR model and for formulation of future models. The greatest contributors to uncertainty in the current model include radiation quality, dose rate effects, and the transfer of exposure-based risk from other populations to an astronaut population. Future formulations of the risk model may benefit from including other potential sources of uncertainty such as space dosimetry, errors in human epidemiology data, and the impact of microgravity and other spaceflight stressors. Here, we discuss the current capabilities of the NSCR-2012 model and several immediate research needs, highlighting areas expected to have an operational impact on the current model schema. The following subway-style route map outlines the NSCR-2012 model (Green Line), emphasizing the research gaps in the Human Research Roadmap for risk of radiation-induced carcinogenesis (Stops on Dashed Lines). The map diagrams how these research gaps feed specific portions of the model.

Description: Of the many possible health challenges posed during extended exploratory missions to space, the effects of space radiation on cardiovascular disease and cancer are of particular concern. There are unique challenges to estimating those radiation risks; care and appropriate and rigorous methodology should be applied when considering small cohorts such as the NASA astronaut population. The objective of this work was to establish whether there is evidence for excess cardiovascular disease or cancer mortality in an early NASA astronaut cohort and determine if a correlation exists between space radiation exposure and mortality.

Description: Since the beginning of manned spaceflight, NASA has recognized the potential risk of cardiovascular decrements due to stressors in the space environment. Of particular concern is the effect of space radiation on cardiovascular disease since astronauts will be exposed to higher levels of galactic cosmic rays outside the Earth's protective magnetosphere. To date, only a few studies have examined the effects of heavy ion radiation on cardiovascular disease, and at lower, space-relevant doses, the association between radiation exposure and cardiovascular pathology is more varied and unclear. Furthermore, other spaceflight conditions such as microgravity, circadian shifts, and confinement stress pose unique challenges in estimating the health risks that can be attributed to exposure to ionizing radiations. In this work, we review age, cause of mortality, and radiation exposure amongst early NASA astronauts in selection groups and discuss the limitations of assessing such a cohort when attempting to characterize the risk of space flight, including stressors such as space radiation and microgravity exposure, on cardiovascular health. METHODS: NASA astronauts in selection groups 1-7 were chosen and the comparison population was white men of the same birth cohort as drawn from data from the CDC Wonder Database and CDC National Center for Health Statistics Life Tables. Cause of death information was obtained from the Lifetime Surveillance of Astronaut Health program and deceased astronauts were classified based on ICD-10 codes: ischemic heart disease (IHD), stroke, cancer, acute occupational events, non-NASA accidents, and other/unknown. Expected years of life left and expected age at death were calculated for the cohort. RESULTS AND CONCLUSIONS: There were 32 deaths in this early astronaut population, 12 of which were due to accidents or acute occupational events that impacted lifespan considerably. The average age at death from these causes is 30 years lower than the average expected ~70 years of age in the general population. Remarkably, all 41 living early astronauts outlived our calculated expected age at death for members of their birth cohort; furthermore, 13 of the 20 deceased astronauts who did not die in NASA/non-NASA accidents exceeded this age. There was no difference in IHD between the astronaut cohort and the comparison population; therefore, it is not possible to associate IHD mortality with radiation in that astronaut cohort. As NASA looks toward future exploration-class missions, early astronaut cohorts provide a convenient option for assessing these risks and for developing mitigation strategies. However, many challenges still exist when assessing such limited evidence, including small cohort size, health and lifestyle confounders (such as smoking and drinking), the high accident mortality rate, and the fact that many of these astronauts are still alive, outliving many of their birth-cohort peers. Future analysis should include a longitudinal study, monitoring cases as they occur in the cohort. As this cohort is currently followed-up over time, and as more IHD cases are anticipated in a population of this age, this type of study is not as resource-intensive as would normally be the case.

Description: Of the many possible health challenges posed during extended exploratory missions to space, the effects of space radiation on cardiovascular disease and cancer are of particular concern. There are unique challenges to estimating those radiation risks; care and appropriate and rigorous methodology should be applied when considering small cohorts such as the NASA astronaut population. The objective of this work was to determine if there was sufficient evidence for excess risk of cardiovascular disease and cancer in early NASA astronaut cohorts. NASA astronauts in selection groups 1-7 were chosen; this relatively homogeneous cohort consists of 73 white males, who unlike today's astronauts, maintained similar smoking and drinking habits to the general US population, and have published radiation doses. The participants flew in space on missions Mercury through Shuttle and received space radiation doses between 0-74.1 milligrays. Cause of death information was obtained from the Lifetime Surveillance of Astronaut Health (LSAH) program at NASA Johnson Space Center. Mortality was compared with the US male population. Trends of mortality with dose were assessed using a logistic model, fitted by maximum likelihood. Only 32 (43.84 percent) of the 73 early astronauts have died. Standard mortality ratios (SMRs) for cancer (n=7, SMR=43.4, 95 percent CI 17.8, 84.9), all circulatory disease (n=7, SMR=33.2, 95 percent CI 13.7, 65.0), and ischemic heart disease (IHD) (n=5, SMR=40.1, 95 percent CI 13.2, 89.4) were significantly lower than for the US white male population. For cerebrovascular disease, the upper confidence interval for SMR included 100, indicating it was not significantly different from the US population (n=2, SMR = 77.0, 95 percent CI 9.4, 268.2). The power of the study is low and remains below 10 percent even when risks 10 times those reported in the literature are assumed. Due to small sample size, there is currently insufficient statistical power to evaluate space radiation exposure effects on mortality in NASA astronauts. In addition to a comprehensive longitudinal study of NASA astronauts, a research strategy of low dose epidemiology data integration with cell and animal studies should be utilized for space radiation risk assessment in the astronauts.

Description: NASA limits astronaut radiation exposures to a 3% risk of exposure-induced death from cancer (REID) at the upper 95% confidence level. Since astronauts approach this limit, it is important that the estimate of REID be as accurate as possible. The NASA Space Cancer Risk 2012 (NSCR-2012) model has been the standard for NASA's space radiation protection guidelines since its publication in 2013. The model incorporates elements from U.S. baseline statistics, Japanese atomic bomb survivor research, animal models, cellular studies, and radiation transport to calculate astronaut baseline risk of cancer and REID. The NSCR model is under constant revision to ensure emerging research is incorporated into radiation protection standards. It is important to develop guidelines, however, to determine what new research is appropriate for integration. Certain standards of transparency are necessary in order to assess data quality, statistical quality, and analytical quality. To this effect, all original source code and any raw data used to develop the code are required to confirm there are no errors which significantly change reported outcomes. It is possible to apply a clinical trials approach to select and assess the improvement concepts that will be incorporated into future iterations of NSCR. This poster describes the five phases of clinical trials research, pre-clinical research, and clinical research phases I-IV, explaining how each step can be translated into an appropriate NSCR model selection guideline.

Description: Historically, the relative biological effectiveness (RBE) has been calculated to quantify the difference between heavy ion and gamma ray radiation. The RBE is then applied to gamma ray data to predict the effects of heavy ions in humans. The RBE is an iso-effect dose-to-dose ratio which, due to its counterintuitive nature, has been commonly miscalculated as an iso-dose effect-to-effect ratio. A paper recently published by Shuryak et al described this second measure intentionally for the first time in 2017, referring to it as the radiation effects ratio (RER). In this study, we utilized simulations to test the ability of both the RBE and the RER to predict known heavy ion effects. RBEs and RERs were calculated using mouse data from Chang et al, and the ability of the RBE and RER to predict the heavy ion data from which they were calculated was verified. Statistical transformations often utilized during data analysis were applied to the gamma and heavy ion data to determine whether RBE and RER are each uniquely defined measures. Scale changes are expected when translating effects from mice to humans and between human populations; gamma and heavy ion data were transformed to represent potential scale changes. The ability of the RBE and RER to predict the transformed heavy ion data from the transformed gamma data was then tested. The RBE but not the RER was uniquely defined after all statistical transformations. The RBE correctly predicted the scale-transformed heavy ion data, while the RER did not. This presentation describes potential implications for both metrics in light of these findings.