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CPRIT/Johnson Space Center, September, 2011 (Cancer Prevention and Research Institute of Texas)

JSC researchers study carcinogenesis, cancer prevention and treatment along with epidemiological (primarily retrospective and longitudinal) studies, modeling, and interactions with the environment such as radiation, nutritional, and endocrine changes related to space flight along with behaviors such as smoking. Cancer research is a major focus for human space flight due to the exposure to space radiation which consists of particles of varying charges and energies, and secondary neutrons. The JSC laboratories collaborate with investigators from the U.S. as well as our European and Japanese partners. We use accelerator facilities at the Brookhaven National Laboratory, Loma Linda University and Los Alamos National Laboratory that generate high energy charged particles and neutrons to simulate cosmic radiation and solar particle events. The research using cultured cells and animals concentrates on damage and repair from the level of DNA to organ tissues, due to exposure to simulated space radiation exposure, that contribute to the induction of leukemia and solid tumors in most major tissues such as lung, colon, liver and breast. The goal of the research is to develop a mathematical model that can predict cancer morbidity and mortality risks with sufficient accuracy for a given space mission.

Davis, Jeffrey↗

Immune Function and Reactivation of Latent Viruses

A major concern associated with long-duration space flight is the possibility of infectious diseases posing an unacceptable medical risk to crew members. One major hypothesis addressed in this project is that space flight will cause alterations in the immune system that will allow latent viruses that are endogenous in the human population to reactivate and shed to higher levels than normal, which may affect the health of crew members. The second major hypothesis being examined is that the effects of space flight will alter the mucosal immune system, the first line of defense against many microbial infections, including herpesviruses, polyomaviruses, and gastroenteritis viruses, rendering crew members more susceptible to virus infections across the mucosa. We are focusing the virus studies on the human herpesviruses and polyomaviruses, important pathogens known to establish latent infections in most of the human population. Both primary infection and reactivation from latent infection with these groups of viruses (especially certain herpesviruses) can cause a variety of illnesses that result in morbidity and, occasionally, mortality. Both herpesviruses and polyomaviruses have been associated with human cancer, as well. Effective vaccines exist for only one of the eight known human herpesviruses and available antivirals are of limited use. Whereas normal individuals display minimal consequences from latent viral infections, events which alter immune function (such as immunosuppressive therapy following solid organ transplantation) are known to increase the risk of complications as a result of viral reactivations.

Butel, Janet S.↗

Technical Evaluation of the NASA Model for Cancer Risk to Astronauts Due to Space Radiation

At the request of NASA, the National Research Council's (NRC's) Committee for Evaluation of Space Radiation Cancer Risk Model1 reviewed a number of changes that NASA proposes to make to its model for estimating the risk of radiation-induced cancer in astronauts. The NASA model in current use was last updated in 2005, and the proposed model would incorporate recent research directed at improving the quantification and understanding of the health risks posed by the space radiation environment. NASA's proposed model is defined by the 2011 NASA report Space Radiation Cancer Risk Projections and Uncertainties--2010 . The committee's evaluation is based primarily on this source, which is referred to hereafter as the 2011 NASA report, with mention of specific sections or tables. The overall process for estimating cancer risks due to low linear energy transfer (LET) radiation exposure has been fully described in reports by a number of organizations. The approaches described in the reports from all of these expert groups are quite similar. NASA's proposed space radiation cancer risk assessment model calculates, as its main output, age- and gender-specific risk of exposure-induced death (REID) for use in the estimation of mission and astronaut-specific cancer risk. The model also calculates the associated uncertainties in REID. The general approach for estimating risk and uncertainty in the proposed model is broadly similar to that used for the current (2005) NASA model and is based on recommendations by the National Council on Radiation Protection and Measurements. However, NASA's proposed model has significant changes with respect to the following: the integration of new findings and methods into its components by taking into account newer epidemiological data and analyses, new radiobiological data indicating that quality factors differ for leukemia and solid cancers, an improved method for specifying quality factors in terms of radiation track structure concepts as opposed to the previous approach based on linear energy transfer, the development of a new solar particle event (SPE) model, and the updates to galactic cosmic ray (GCR) and shielding transport models. The newer epidemiological information includes updates to the cancer incidence rates from the life span study (LSS) of the Japanese atomic bomb survivors, transferred to the U.S. population and converted to cancer mortality rates from U.S. population statistics. In addition, the proposed model provides an alternative analysis applicable to lifetime never-smokers (NSs). Details of the uncertainty analysis in the model have also been updated and revised. NASA's proposed model and associated uncertainties are complex in their formulation and as such require a very clear and precise set of descriptions. The committee found the 2011 NASA report challenging to review largely because of the lack of clarity in the model descriptions and derivation of the various parameters used. The committee requested some clarifications from NASA throughout its review and was able to resolve many, but not all, of the ambiguities in the written description.

Source record↗

Technical Evaluation of the NASA Model for Cancer Risk to Astronauts Due to Space Radiation

At the request of NASA, the National Research Council's (NRC's) Committee for Evaluation of Space Radiation Cancer Risk Model reviewed a number of changes that NASA proposes to make to its model for estimating the risk of radiation-induced cancer in astronauts. The NASA model in current use was last updated in 2005, and the proposed model would incorporate recent research directed at improving the quantification and understanding of the health risks posed by the space radiation environment. NASA's proposed model is defined by the 2011 NASA report Space Radiation Cancer Risk Projections and Uncertainties 2010 (Cucinotta et al., 2011). The committee's evaluation is based primarily on this source, which is referred to hereafter as the 2011 NASA report, with mention of specific sections or tables cited more formally as Cucinotta et al. (2011). The overall process for estimating cancer risks due to low linear energy transfer (LET) radiation exposure has been fully described in reports by a number of organizations. They include, more recently: (1) The "BEIR VII Phase 2" report from the NRC's Committee on Biological Effects of Ionizing Radiation (BEIR) (NRC, 2006); (2) Studies of Radiation and Cancer from the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR, 2006), (3) The 2007 Recommendations of the International Commission on Radiological Protection (ICRP), ICRP Publication 103 (ICRP, 2007); and (4) The Environmental Protection Agency s (EPA s) report EPA Radiogenic Cancer Risk Models and Projections for the U.S. Population (EPA, 2011). The approaches described in the reports from all of these expert groups are quite similar. NASA's proposed space radiation cancer risk assessment model calculates, as its main output, age- and gender-specific risk of exposure-induced death (REID) for use in the estimation of mission and astronaut-specific cancer risk. The model also calculates the associated uncertainties in REID. The general approach for estimating risk and uncertainty in the proposed model is broadly similar to that used for the current (2005) NASA model and is based on recommendations by the National Council on Radiation Protection and Measurements (NCRP, 2000, 2006). However, NASA's proposed model has significant changes with respect to the following: the integration of new findings and methods into its components by taking into account newer epidemiological data and analyses, new radiobiological data indicating that quality factors differ for leukemia and solid cancers, an improved method for specifying quality factors in terms of radiation track structure concepts as opposed to the previous approach based on linear energy transfer, the development of a new solar particle event (SPE) model, and the updates to galactic cosmic ray (GCR) and shielding transport models. The newer epidemiological information includes updates to the cancer incidence rates from the life span study (LSS) of the Japanese atomic bomb survivors (Preston et al., 2007), transferred to the U.S. population and converted to cancer mortality rates from U.S. population statistics. In addition, the proposed model provides an alternative analysis applicable to lifetime never-smokers (NSs). Details of the uncertainty analysis in the model have also been updated and revised. NASA's proposed model and associated uncertainties are complex in their formulation and as such require a very clear and precise set of descriptions. The committee found the 2011 NASA report challenging to review largely because of the lack of clarity in the model descriptions and derivation of the various parameters used. The committee requested some clarifications from NASA throughout its review and was able to resolve many, but not all, of the ambiguities in the written description.

Source record↗

Use of Longitudinal Serum Analysis and Machine Learning to Develop a Classifier for Cancer Early Detection

Early detection of solid tumors through a simple screening process, such as the proteomic analysis of biofluids, has the potential to significantly alter the management and outcomes of cancers. The application of advanced targeted proteomics measurements and data analysis strategies to uniformly collected serum or plasma samples would enable longitudinal studies of cancer risk, progression, and response to therapy that have the potential to significantly reduce cancer burden in general. In this article, we describe a generalizable workflow combining robust, multiplexed targeted proteomics measurements applied to longitudinal samples from the Department of Defense Serum Repository with a Random Forest machine learning method for developing and initially evaluating the performance of candidate biomarker panels for early detection of cancers. The effectiveness of this approach was demonstrated in a cohort of 175 head and neck squamous cell carcinoma patients. The outlined protocols include methods for sample preparation, instrument analysis, and data analysis and interpretation using this workflow.

Longitudinal analysis, machine learning, cancer, e↗

In-Situ Spectrometry of Neutrons

High energy charged particles of extra-galactic, galactic and solar origin collide with spacecraft structures in Earth orbit outside the atmosphere and in interplanetary travel beyond the Earth's magnetosphere. These primaries create a number of secondary particles inside the structures that can produce a significant ionizing radiation environment. This radiation is a threat to long term inhabitants or travelers for space missions and produces an increased risk of cancer and DNA damage. The primary high energy cosmic rays and trapped protons collide with common spacecraft materials such as aluminum and silicon and create secondary particles inside structures that are mostly protons and neutrons. Charged protons are readily detected and instruments are already in existence for this task. Neutrons are electrically neutral and therefore much more difficult to measure and detect. These neutrons are reported to contribute 30-60% of the dose inside space structures and cannot be ignored. Currently there is no compact, portable and real time neutron detector instrumentation available for use inside spacecraft or on planetary surfaces where astronauts will live and work. We propose to design and build a portable, low power and robust neutron spectrometer that will measure the neutron spectrum from 10 KeV to 500 MeV with at least 10% energy resolution in the various energy intervals. This instrument will monitor the existing neutron environment both inside spacecraft structures and on planetary surfaces to determine the safest living areas, warn of high fluxes associated with solar storms and assist the NSBRI Radiation Effects Team in making an accurate assessment of increased cancer risk and DNA damage to astronauts. The instrument uses a highly efficient proportional counter Helium 3 tube at the lowest energy intervals where .equivalent damage factors for tissue are the highest (10 KeV-2 MeV). The Helium 3 tube may be shielded with a cadmium absorber to eliminate the much less damaging, but more prevalent, thermal and epithermal neutrons and to make the structure of the spectrum more accurate in the 20 KeV-2 MeV range; or a pair of tubes, one shielded and one unshielded, can be combined so that the difference in their counts yields the thermal neutron contribution. The spectrometer also uses a 5mm lithium drifted bulk silicon solid state detector in the medium energy range of 2-20 Mev and two standard silicon surface barrier detectors separated by tens of millimeters behind a I cm thick polyethylene moderator in a stack or telescope arrangement for the high energy neutrons (>20 MeV). In the medium and high energy regions equivalent damage factors are lower but hits from one or a small number of neutrons may prove to be important. The silicon detector systems for medium and high energy neutrons will discriminate against charged particles by using a plastic cesium iodide scintillator of an appropriate geometry monitored by a silicon PIN photodiode.

Maurer, Richard H.↗

Health Hazards of Exposures to Radioiodine

Iodine is a chemical element with atomic number 53. Iodine-127 is stable (non-radioactive) and commonly found in nature. Elemental iodine is a purple-colored solid at room temperature and pressure, but spontaneously sublimates (turns into vapor). Iodine is an essential element for life, and is required for proper functioning of the thyroid. Iodine is present in many foods, and is readily absorbed by the body and concentrated in the thyroid gland. A fraction of iodine ingested or inhaled is rapidly removed by the kidneys. The rest of the inhaled or ingested iodine is absorbed the by thyroid and retained for many months. Iodine has a biological half-life of approximately 120 days in health individuals. The biological half-life can be shorter in individuals with hyperthyroidism, and longer in individuals with hypothyroidism. Iodine has a number of radioactive isotopes, most of which have relatively short half-lives (days or weeks). Short half-life iodine isotopes are useful for a variety of medical applications, including imaging and cancer therapy. For example, Iodine-123 (half-life 13 hours) is commonly used for medical imaging of the thyroid, while iodine-131 (half-life 8 days) is used for suppressing thyroid function in individuals with hyperthyroidism or ablating (killing) thyroid cells to treat thyroid cancer. Iodine-125 (half-life 59 days) is produced in nuclear reactors, and has medical uses. Although iodine-125 can be used for thyroid imaging, Iodine-123 is more commonly used for that purpose because of its shorter half-life and higher-energy emissions. Iodine-125 is more commonly used for cancer treatment, and can be processed into small metal pellets (seeds) inserted directly into a tumor. Iodine-125 emits low-energy x-rays which can kill tumor cells and generally cannot escape the tumor, sparing other tissues. Medical iodine for imaging or treatment is typically administered orally in the form a pill or liquid solution. A typical adult thyroid scan using iodine-123 involves having the patient swallow between one and four 0.1 millicuries pills, with the exact dose dependent on the patient’s weight. This results in a whole-body committed effective dose of 80 – 320 mrem, and a thyroid equivalent dose of 1443 – 5772 mrem. Note that the whole-body effective dose relates to the overall cancer risk, while the larger equivalent dose to the thyroid only indicates that most of this risk is the result of exposure to the thyroid. These doses are considered safe, although the procedure is not recommended for pregnant or breastfeeding women. In contrast, the quantities of iodine-131 used for treatment of hyperthyroidism and thyroid cancers are much higher. For treatment of hyperthyroidism, 4 – 10 millicuries are administered, while for thyroid cancer the administration can range from 50 – 150 millicuries of I-131. In addition to medical exposures, large populations were exposed to radioiodine as result of the atomic bombings of Hiroshima and Nagasaki in Japan, and the Chernobyl nuclear accident. These populations have been carefully followed for many years to assess the effect of their radiation exposures on cancer risk. As a result, a great deal is known about the cancer risks associated with radioiodine exposure. Because iodine is concentrated in the thyroid, the principal risk of exposure to radioiodine is thyroid cancer. Children have the highest risk of thyroid cancer after exposure to radioactive iodine. According to a large study of Japanese atomic bomb survivors, an effective dose of one Sievert (100,000 mrem) has been observed to increase the risk of thyroid cancer by a factor of 9.5 in children aged zero to nine years old, by a factor of 3 in children aged 10 to 19 years old, and by barely detectable amounts in adults. Another way of quantifying the risk from radioiodine exposure is from risk coefficients, which provide the risk per unit intake of radionuclides in terms of both morbidity (any cancer) and mortality (death). Both morbidity (risk of cancer) and mortality (death) risks are shown in the table below. Note that because thyroid cancer is almost never fatal, the morbidity coefficients are much larger than the mortality coefficients.

61 RADIATION PROTECTION AND DOSIMETRY↗