Comparison of lifetime mortality risk, incidence risk, and DALYs of baseline cancer rates among countries as a benchmark for radiation-related cancer risk.

Statistical benchmark data are necessary when considering the basis for radiation protection criteria based on calculated risks. We herein focused on baseline mortality and incidence cancer rates as benchmark data collected from 33 countries. Furthermore, we calculated the lifetime mortality and incidence risks and disability-adjusted life years (DALYs) for all solid cancers, colon cancer, lung cancer, breast cancer, thyroid cancer, and leukemia using the baseline cancer rates and compared them among the countries. The results showed that the lifetime mortality and incidence risks and DALYs for all solid cancers differed among the countries by a factor of 2-4 for males and 2-3 for females; these were low in less-developed countries. Our study proposed that health risk based on baseline cancer rates should be the benchmark for comparing radiation cancer risks.

Low Dose Radiation and Solid Tumors Mortality Risk.

BACKGROUND: US nuclear capable shipyard workers have increased potential for occupational radiation exposure. OBJECTIVE: The aim of the study is to examine solid tumor mortality risks at low doses. METHOD: 437,937 workers working from 1957 to 2004 at eight US shipyards were studied. RESULTS: Radiation workers with a median life-time dose at 0.82 mSv had a significantly lower solid tumor mortality risk (relative risk [RR]: 0.96, 95% confidence interval [CI]: 0.94-0.98) than nonradiation workers. Among 153,930 radiation workers, the RRs of solid tumors increased with increasing dose categories without statistical significance. The dose category >0-<25 mSv had significantly lower RR (0.95, 95% CI: 0.91-0.99) versus 0 dose and the excess relative risk was 0.05/100 mSv (95% CI: 0.01-0.08). CONCLUSIONS: Solid tumor risk might increase with radiation dose, but not linearly at low doses. Actual mortality risk may be dependent on dose received.

The Hiroshima A-Bomb Black Rain and the Lifespan Study; A Resolution of the Enigma.

The Japanese Lifespan Study (LSS) of the A-Bomb survivors is the principal basis of the current legal radiological framework. Evidence provided for the first time here shows that internal exposure to radiologically significant quantities of Uranium-234 contained in sub-micron particle rainout from the un-fissioned weapon warhead, the Black Rain, is a missing exposure in the LSS analysis. It is argued that this is responsible for a background excess cancer risk in all the LSS dose groups. This, together with epidemiological evidence based on unexposed controls falsifies the LSS cancer vs. dose regression coefficients for internal exposure.

The Theoretical Value of Whole-Lung Irradiation for COVID-19 Pneumonia: A Reasonable and Safe Solution until Targeted Treatments are Developed.

In this work, we considered the theoretical role of low-dose radiation therapy (approximately 0.5-1.0 Gy) in the treatment of respiratory distress syndrome associated with COVID-19 infection. Monte Carlo calculations were performed to gauge the ability to deliver low-dose radiation to the thoracic mid-plane using an orthovoltage machine. In addition, the potential harm of a single dose of 0.75 Gy (whole-lung irradiation) was assessed based on the recommendations of the BEIR-VII committee of the U.S. National Research Council. Based on the results of this work, it was determined that an orthovoltage machine (minimum 300 kVp) can be used to deliver 0.75 Gy dose to the lungs while respecting cutaneous tolerance. Using data from the BEIR-VII Committee, it is evident that the apparent benefits of such radiation treatment for patients suffering from severe manifestations of the COVID-19 infectious syndrome outweigh the potential loss of life due to radiation-induced malignancy. Although the vaccination against COVID-19 has become a reality, the spread and mortality in severely ill patients remain unacceptably high. The risk of outbreaks in the future is unknown. We suggest herein that low-dose radiotherapy at the bedside should be rigorously considered as a therapeutic option since it appears to be feasible and safe in the short and long term.

Lung Cancer in the Mayak Workers Cohort: Risk Estimation and Uncertainty Analysis.

The workers at the Mayak nuclear facility near Ozyorsk, Russia are a primary source of information about exposure to radiation at low-dose rates, since they were subject to protracted exposures to external gamma rays and to internal exposures from plutonium inhalation. Here we re-examine lung cancer mortality rates and assess the effects of external gamma and internal plutonium exposures using recently developed Monte Carlo dosimetry systems. Using individual lagged mean annual lung doses computed from the dose realizations, we fit excess relative risk (ERR) models to the lung cancer mortality data for the Mayak Workers Cohort using risk-modeling software. We then used the corrected-information matrix (CIM) approach to widen the confidence intervals of ERR by taking into account the uncertainty in doses represented by multiple realizations from the Monte Carlo dosimetry systems. Findings of this work revealed that there were 930 lung cancer deaths during follow-up. Plutonium lung doses (but not gamma doses) were generally higher in the new dosimetry systems than those used in the previous analysis. This led to a reduction in the risk per unit dose compared to prior estimates. The estimated ERR/Gy for external gamma-ray exposure was 0.19 (95% CI: 0.07 to 0.31) for both sexes combined, while the ERR/Gy for internal exposures based on mean plutonium doses were 3.5 (95% CI: 2.3 to 4.6) and 8.9 (95% CI: 3.4 to 14) for males and females at attained age 60. Accounting for uncertainty in dose had little effect on the confidence intervals for the ERR associated with gamma-ray exposure, but had a marked impact on confidence intervals, particularly the upper bounds, for the effect of plutonium exposure [adjusted 95% CIs: 1.5 to 8.9 for males and 2.7 to 28 for females]. In conclusion, lung cancer rates increased significantly with both external gamma-ray and internal plutonium exposures. Accounting for the effects of dose uncertainty markedly increased the width of the confidence intervals for the plutonium dose response but had little impact on the external gamma dose effect estimate. Adjusting risk estimate confidence intervals using CIM provides a solution to the important problem of dose uncertainty. This work demonstrates, for the first time, that it is possible and practical to use our recently developed CIM method to make such adjustments in a large cohort study.

Angiosarcoma associated with radiation therapy after treatment of breast cancer. Retrospective study on ten years.

PURPOSE: The breast sarcoma induced by radiation therapy is rare but increasing, given the increased long-term survival of patients receiving radiation therapy. Fibrosarcoma, histiocytofibroma and angiosarcoma are the most common breast sarcoma. Angiosarcoma is the most common after breast cancer treated by radiation therapy, often diagnosed too late, with a severe prognosis and a high rate of recurrence. However, because of the low incidence of angiosarcoma associated with radiation therapy (AAR), the benefit of radiation therapy in breast cancer treatment outweighs the risk to develop angiosarcoma. The aim of this study is to evaluate these rare cases of AAR diagnosed in eastern Belgium in comparison to the data from the literature. PATIENTS AND METHODS: Nine cases of AAR after radiation for breast ductal carcinoma were included in this retrospective study. AAR was diagnosed according to Cahan criteria between January 2007 and December 2016. Latency, incidence, management and prognosis are comparable to the literature. RESULTS, CONCLUSION: The median latency was 10 (4-24) years, the incidence of AAR in the East Belgian area was 0.09% of the patients irradiated on the same period. Patients were treated by surgery with wide local excision with or without reconstructive surgery, without radiotherapy and chemotherapy treatment. Kaplan-Meier analysis showed median overall survival of 61.8 months, patient survival of 55.6% at one year and 29.6% at five years. With the constant progress of medicine and its technologies, it would be possible to limit the occurrence of AAR or to diagnose it at an earlier stage.

Mortality among individuals exposed to atomic bomb radiation in utero: 1950-2012.

We examined the mortality risks among 2463 individuals who were exposed in utero to atomic bomb radiation in Hiroshima or Nagasaki in August 1945 and were followed from October 1950 through 2012. Individual estimates of mother's weighted absorbed uterine dose (DS02R1) were used. Poisson regression method was used to estimate the radiation-associated excess relative risk per Gy (ERR/Gy) and 95% confidence intervals (CI) for cause-specific mortality. Head size, birth weight, and parents' survival status were evaluated as potential mediators of radiation effect. There were 339 deaths (216 males and 123 females) including deaths from solid cancer (n = 137), lymphohematopoietic cancer (n = 8), noncancer disease (n = 134), external cause (n = 56), and unknown cause (n = 4). Among males, the unadjusted ERR/Gy (95% CI) was increased for noncancer disease mortality (1.22, 0.10-3.14), but not for solid cancer mortality (- 0.18, < - 0.77-0.95); the unadjusted ERR/Gy for external cause mortality was not statistically significant (0.28, < - 0.60-2.36). Among females, the unadjusted ERRs/Gy were increased for solid cancer (2.24, 0.44-5.58), noncancer (2.86, 0.56-7.64), and external cause mortality (2.57, 0.20-9.19). The ERRs/Gy adjusted for potential mediators did not change appreciably for solid cancer mortality, but decreased notably for noncancer mortality (0.39, < - 0.43-1.91 for males; 1.48, - 0.046-4.55 for females) and external cause mortality (0.10, < - 0.57-1.96 for males; 1.38, < - 0.46-5.95 for females). In conclusion, antenatal radiation exposure is a consistent risk factor for increased solid cancer mortality among females, but not among males. The effect of exposure to atomic bomb radiation on noncancer disease and external cause mortality among individuals exposed in utero was mediated through small head size, low birth weight, and parental loss.

Gastrointestinal Cancer Survival and Radiation Exposure among Atomic Bomb Survivors: The Life Span Study.

BACKGROUND: Radiation exposure is an established risk factor for the development of several forms of cancer, including gastrointestinal cancers. However, few studies have investigated the relationship between prediagnostic radiation exposure and survival after cancer diagnosis. METHODS: Participants in the Life Span Study (LSS) of atomic bomb survivors who were diagnosed with a first primary invasive stomach, colon, or rectal cancer between 1958 and 2009 were followed for mortality during 1958-2014. Cox regression models were used to calculate HRs and 95% confidence intervals (CI) for associations of radiation dose from atomic bomb exposure with survival (cancer-specific and overall) after cancer diagnosis. Analyses were adjusted for city of primary exposure, sex, age at diagnosis, and year of diagnosis. RESULTS: We identified 7,728 eligible patients with cancer for analysis. We observed no statistically significant associations between radiation dose and cancer-specific survival among LSS participants with a gastrointestinal cancer. Higher radiation doses (≥1 Gy) were suggestively, but not significantly, associated with modestly poorer cancer-specific survival for colon cancer only (HR, 1.38; 95% CI, 0.90-2.12), and were associated with poorer overall survival regardless of cancer site. CONCLUSIONS: Although radiation exposure is associated with increased risk of gastrointestinal cancer incidence and mortality, study results are inconclusive about an association between prediagnostic radiation exposure and survival after gastrointestinal cancer diagnosis. IMPACT: Radiation exposure from the atomic bomb before gastrointestinal cancer diagnosis was not associated with cancer survival, but should be evaluated in relation to survival for other cancer types.

Solar ultraviolet A radiation and nonmelanoma skin cancer in Arica, Chile.

In this work, we present the maximum daily values of solar ultraviolet A radiation (UV-A) as a function of time. The results indicated that such values reached a maximum of 93.9 W/m2 in 2010 and a minimum of 16.5 W/m2 in 2012. The annual averages of both UV-A and solar ultraviolet B radiation (UV-B) from 2007 to 2013 were recorded. UV-A was always higher than UV-B. However, UV-B is more energetic due to its intrinsic wavelength. The nonmelanoma skin cancer mortality incidences per 100,000 inhabitants in Arica and in Chile as a function of time between 2007 and 2013 indicated that these mortality rates varied from 3.12 (Arica) to 0.88 (Chile) in 2007 and 2.71 (Arica) to 0.88 (Chile) in 2013. The nonmelanoma skin cancer prevalence rates per 100,000 inhabitants in Arica were 22.2 in 2007 and 19.5 in 2013. The relationship between NMSC and exposure to UV-A is given. In Arica, we report high levels of UV-A and the highest NMSC rates compared with other regions in our country.

Estimation of Dose-Rate Effectiveness Factor for Malignant Tumor Mortality: Joint Analysis of Mouse Data Exposed to Chronic and Acute Radiation.

Uncertainties due to confounding factors in epidemiological studies have limited our knowledge of the effects of low-dose-rate chronic exposure on human health. Animal experiments, wherein each subject is considered to be nearly identical, can complement the limitations of epidemiological studies. Therefore, we conducted a joint analysis of previously published cancer mortality data in B6C3F1 female mice chronically and acutely irradiated with 137Cs γ rays to estimate the dose-rate effectiveness factor. In the chronically irradiated animal experiment conducted by the Institute for Environmental Sciences, mice received irradiation at dose rates of 0.05, 1.1 or 21 mGy per day for 400 days from 8 weeks of age. For the acutely irradiated animal experiment conducted by the National Institute of Radiological Sciences, mice received irradiation at 35, 105, 240 or 365 days of age with 1.9, 3.8 or 5.9 Gy at a dose rate of 0.98 Gy per min. Because the preliminary analyses suggested that the risk was dependent on the age at exposure, a model was applied that considered risk differences depending on this factor. The model analysis revealed a three-fold, significantly decreased risk per Gy in mice exposed to 21 mGy per day compared to that in acutely irradiated mice. This resulted in a dose-rate effectiveness factor larger than that reported previously.

Occupational radiation and haematopoietic malignancy mortality in the retrospective cohort study of US radiologic technologists, 1983-2012.

OBJECTIVES: To evaluate cumulative occupational radiation dose response and haematopoietic malignancy mortality risks in the US radiologic technologist cohort. METHODS: Among 110 297 radiologic technologists (83 655 women, 26 642 men) who completed a baseline questionnaire sometime during 1983-1998, a retrospective cohort study was undertaken to assess cumulative, low-to-moderate occupational radiation dose and haematopoietic malignancy mortality risks during 1983-2012. Cumulative bone marrow dose (mean 8.5 mGy, range 0-430 mGy) was estimated based on 921 134 badge monitoring measurements during 1960-1997, work histories and historical data; 35.4% of estimated doses were based on badge measurements. Poisson regression was used to estimate excess relative risk of haematopoietic cancers per 100 milligray (ERR/100 mGy) bone-marrow absorbed dose, adjusting for attained age, sex and birth year. RESULTS: Deaths from baseline questionnaire completion through 2012 included 133 myeloid neoplasms, 381 lymphoid neoplasms and 155 leukaemias excluding chronic lymphocytic leukaemia (CLL). Based on a linear dose-response, no significant ERR/100 mGy occurred for acute myeloid leukaemia (ERR=0.0002, 95% CI <-0.02 to 0.24, p-trend>0.5, 85 cases) or leukaemia excluding CLL (ERR=0.05, 95% CI <-0.09 to 0.24, p-trend=0.21, 155 cases). No significant dose-response trends were observed overall for CLL (ERR<-0.023, 95% CI <-0.025 to 0.18, p-trend=0.45, 32 cases), non-Hodgkin lymphoma (ERR=0.03, 95% CI <-0.2 to 0.18, p-trend=0.4, 201 cases) or multiple myeloma (ERR=0.003, 95% CI -0.02 to 0.16, p-trend>0.5, 112 cases). Findings did not differ significantly by demographic factors, smoking or specific radiological procedures performed. CONCLUSION: After follow-up averaging 22 years, there was little evidence of a relationship between occupational radiation exposure and myeloid or lymphoid haematopoietic neoplasms.

Solar UV Exposure and Mortality from Skin Tumors: An Update.

Solar UV exposure is critical and complex in the etiology and prognosis of skin cancer, particularly cutaneous malignant melanoma. Sun exposure and one of its "derivatives," vitamin D, have been implicated in protection against mortality from melanoma. However, the relationships are inconsistent. At this time, it is not possible to make clear recommendations for or against sun exposure in relationship to melanoma prognosis. However, this relationship deserves continued exploration.

Lifetime Mortality Risk from Cancer and Circulatory Disease Predicted from the Japanese Atomic Bomb Survivor Life Span Study Data Taking Account of Dose Measurement Error.

Dosimetric measurement error is known to potentially bias the magnitude of the dose response, and can also affect the shape of dose response. In this report, generalized relative and absolute rate models are fitted to the latest Japanese atomic bomb survivor solid cancer, leukemia and circulatory disease mortality data (followed from 1950 through 2003), with the latest (DS02R1) dosimetry, using Bayesian techniques to adjust for errors in dose estimates and assessing other model uncertainties. Linear-quadratic models are fitted and used to assess lifetime mortality risks for contemporary UK, USA, French, Russian, Japanese and Chinese populations. For a test dose of 0.1 Gy absorbed dose weighted by neutron relative biological effectiveness, solid cancer, leukemia and circulatory disease mortality risks for a UK population using a generalized linear-quadratic relative rate model were estimated to be 3.88% Gy-1 [95% Bayesian credible interval (BCI): 1.17, 6.97], 0.35% Gy-1 (95% BCI: -0.03, 0.78) and 2.24% Gy-1 (95% BCI: -0.17, 13.76), respectively. Using a generalized absolute rate linear-quadratic model at 0.1 Gy, the lifetime risks for these three end points were estimated to be 3.56% Gy-1 (95% BCI: 0.54, 6.78), 0.41% Gy-1 (95% BCI: 0.01, 0.86) and 1.56% Gy-1 (95% BCI: -1.10, 7.21), respectively. There was substantial evidence of curvature for solid cancer (in particular, the group of solid cancers excluding lung, breast and stomach cancers) and leukemia, so that for solid cancer and leukemia, estimates of excess risk per unit dose were nearly doubled by increasing the dose from 0.01 to 1.0 Gy, with most of the increase occurring in the interval from 0.1 to 1.0 Gy. For circulatory disease, the dose-response curvature was inverse, so that risk per unit dose was nearly halved by going from 0.01 t o 1.0 Gy weighted absorbed dose, although there were substantial uncertainties. In general, there were higher radiation risks for females compared to males. This was true for solid cancer and circulatory disease overall, as well as for lung, breast, stomach and the group of other solid cancers, and was the case whether relative or absolute rate projection models were employed; however, for leukemia this pattern was reversed. Risk estimates varied somewhat between populations, with lower cancer risks in aggregate for China and Russia, but higher circulatory disease risks for Russia, particularly using the relative rate model. There was more pronounced variation for certain cancer sites and certain types of projection models, so that breast cancer risk was markedly lower in China and Japan using a relative rate model, but the opposite was the case for stomach cancer. There was less variation between countries using the absolute rate models for stomach cancer and breast cancer, but this was not the case for lung cancer and the group of other solid cancers, or for circulatory disease.

Cancer incidence and mortality following treatment of hyperthyroidism with radioactive iodine.

PURPOSE OF REVIEW: Hyperthyroidism is a commonly encountered clinical issue. Radioactive iodine is one of the treatment modalities employed over the last 80 years. Prior studies are conflicting as to whether radioactive iodine is associated with an increased risk of subsequent malignancy and associated mortality. The present article reviews recent publications on this subject. RECENT FINDINGS: Two recent studies make meaningful contributions to the existing literature; however, data remain inconsistent. The first, conducted using the Clalit Health Services database, evaluated solid tumor incidence after radioactive iodine and found no association with increased risk of solid tumor malignancy. The second, which is an updated analysis of the Cooperative Thyrotoxicosis Therapy Follow-up Study, concluded that there is a dose-dependent increased risk of solid tumor mortality using a novel method of estimating organ-specific radiation exposure. SUMMARY: In patients with hyperthyroidism, radioactive iodine is a popular and effective treatment option. Prior studies reach conflicting conclusions on the potential relationship between radioactive iodine and both subsequent cancer incidence and mortality. We review recent publications that add to our understanding of this important clinical question.

Lung cancer mortality associated with protracted low-dose occupational radiation exposures and smoking behaviors in U.S. radiologic technologists, 1983-2012.

In the Japanese atomic bomb survivors, risk of lung cancer has been shown to increase with greater acute exposure to ionizing radiation. Although similar findings have been observed in populations exposed to low-dose, protracted radiation, such studies lack information on cigarette smoking history, a potential confounder. In a cohort of 106 068 U.S. radiologic technologists, we examined the association between estimated cumulative lung absorbed dose from occupational radiation exposure and lung cancer mortality. Poisson regression models, adjusted for attained age, sex, birth cohort, pack-years smoked and years since quitting smoking, were used to calculate linear excess relative risks (ERR) per 100 mGy, using time-dependent cumulative lung absorbed dose, lagged 10 years. Mean cumulative absorbed dose to the lung was 25 mGy (range: 0-810 mGy). During the 1983 to 2012 follow-up, 1090 participants died from lung cancer. Greater occupational radiation lung dose was not associated with lung cancer mortality overall (ERR per 100 mGy: -0.02, 95% CI: <0-0.13). However, significant dose-response relationships were observed for some subgroups, which might be false-positive results given the number of statistical tests performed. As observed in other studies of radiation and smoking, the interaction between radiation and smoking appeared to be sub-multiplicative with an ERR per 100 mGy of 0.41 (95% CI: 0.01-1.15) for those who smoked <20 pack-years and -0.03 (95% CI: <0-0.15) for those who smoked ≥20 pack-years. Our study provides some evidence that greater protracted radiation exposure in the low-dose range is positively associated with lung cancer mortality.

Innovations in applied decision theory for health and safety.

OBJECTIVES: There are established methods for occupational epidemiological cohort analysis, such as proportional hazards regression, that are well suited to aetiological research and yield parameter estimates that allow for succinct communication among academics. However, these methods are not necessarily well suited for evaluation of health impacts of policy choices and communication to decision makers. An informed decision about a policy that impacts health and safety requires a valid estimate of the policy's potential impact. METHODS: We propose methods for data summarisation that may facilitate communication with managers, workers and their advocates. We calculate measures of effect in a framework for competing events, graphically display potential impacts on cause-specific mortality under policy alternatives and contrast these results to estimates obtained using standard Poisson regression methods. Methods are illustrated using a cohort mortality study of 28 546 Ontario uranium miners hired between 1950 and 1996 and followed through 2007. RESULTS: A standard regression analysis yields a positive association between cumulative radon progeny exposure and all-cause mortality (log(RR per 100 WLM)=0.09; SE=0.02). The proposed method yields an estimate of the expected gain in life expectancy (approximately 6 months per worker) and reduction of 261 lung cancer deaths under a policy that eliminated occupational radon progeny exposure. CONCLUSIONS: The proposed method shifts attention from covariate-adjusted risk ratios or rate ratios to estimates of deaths that are avoided or delayed under a potential policy. The approach may help inform decision-making and strengthen the connection of epidemiological approaches to data analysis with developments in decision theory and systems engineering to improve health and safety.

Administration of lower doses of radium-224 to ankylosing spondylitis patients results in no evidence of significant overall detriment.

The use of low doses of radium-224 (224Ra) chloride for the treatment of ankylosing spondylitis was stopped following the discovery that patients treated with it had a higher than control incidence of leukaemia and other cancers. This was so even though the treatment resulted in decreased pain and increased mobility-both of which are associated with decreased mortality. It was decided to re-analyze the epidemiological data looking at all causes of death. The risk of leukaemia, solid cancer, death from non-cancer causes and from all causes in a study populations of men that received either the typical dose of 5.6 to 11.1 MBq of 224Ra, any dose of 224Ra or no radium were compared using the Cox proportional hazard model. For patients that received the typical dose of 224Ra agreed with the excess cancer was similar to that reported in previous studies. In contrast, these patients were less likely to die from non-cancer diseases and from all causes of death than the control patients. No excess mortality was also found in the population of all males that received the radionuclide. It is concluded that 224Ra treatment administered at low doses to patients with ankylosing spondylitis did not impact mortality from all causes. The study demonstrates the need to consider all causes of death and longevity when assessing health impacts following irradiation.

Does muscle invasive bladder cancer following pelvic radiotherapy portend worse prognosis? A seer-based study.

BACKGROUND: Although emerging evidence demonstrates increased risk of secondary bladder cancer following pelvic radiotherapy, the aggressiveness of these tumors is not well-characterized. MATERIALS AND METHODS: A search of the Surveillance, Epidemiology, and End Results (SEER) 18 Database, identified 25,734 patients diagnosed with bladder cancer following definitive therapy for previous pelvic malignancy. Kaplan-Meier curve analyses were utilized to determine overall survival with significance set at p<0.05. RESULTS: Of the 25,734 patients, 11,376 (44.2%) received radiation treatment for their first cancer. Overall survival of bladder cancer was found to be 80%, 69.5%, and 49.2% at 1,2 and 5 years, respectively. There was no significant survival difference between groups whose first cancer was treated with or without radiation (p=0.8). A survival advantage was seen for the bladder cancer patients not treated with radiation for cervical (p=0.004), uterine (p=0.0006), and vaginal cancers (p<0.0001). Bladder cancer patients treated with radiation for prostate cancer showed a survival advantage (p=0.002). The average time to second cancer diagnosis was 6.5±6.1 years. Patients treated with radiation for first primary cancer showed a longer time to second cancer (7.2±6.0 years) compared to those treated without radiation (5.9±6.0 years) (p<0.01). CONCLUSION: Patients with prior history of female cancers treated without radiation demonstrated significant survival advantage in second primary bladder cancer. A small significant survival advantage was seen in bladder cancer patients previously treated for prostate cancer with radiation. This data suggests that second primary bladder cancer following pelvic radiotherapy has similar biologic aggressiveness to urothelial carcinoma developing without a history of radiotherapy. MICROABSTRACT: The overall survival of 25,734 patients diagnosed with bladder cancer following definitive therapy for a previous pelvic malignancy was 49.2% at 5 years. There was no significant survival difference between groups whose first cancer was treated with or without radiation. Second primary bladder cancer following pelvic radiotherapy has similar biologic aggressiveness to urothelial carcinoma developing without a history of radiotherapy.

A methodology for investigating the impact of medical countermeasures on the risk of exposure induced death.

The space radiation environment is composed of ionizing particles that may pose health risks to crew members during Low Earth Orbit (LEO) and deep space missions. NASA has established astronaut career radiation limits for cancer of 3% Risk of Exposure Induced Death (REID) at the 95% confidence level. The REID is the increased lifetime risk of death from cancer due to radiation exposure in comparison to an unexposed background population and has been traditionally mitigated by passive shielding design concepts and limiting safe days in space. Additional reduction in radiation exposure risk may be achieved with Medical Countermeasures (MCM). Recent meta-analyses have demonstrated the efficacy of aspirin in the reduction of the background colorectal cancer incidence and mortality rates for specific cohorts. Additional studies of warfarin in patients greater than 50 years of age have indicated statistically significant decreases in stomach, bladder, brain, prostate, and lung cancer incidence as compared to control groups. While ultimate selection of suitable countermeasures will be the responsibility of flight surgeons, this paper presents a general methodology for incorporating MCM into the NASA Space Radiation Cancer Risk model and includes modifications of the background mortality rates (hazard rates) and the radiation risk coefficients to numerically quantify the benefits of MCM. As examples of the method, aspirin and warfarin will be employed as MCM in a sensitivity analysis to compute the REID for astronauts embarking on a one-year deep space mission scenario.