Secondary cancer risk assessment in healthy organs following craniospinal irradiation.

INTRODUCTION: Medulloblastoma is a central nerves tumor that often occurs in pediatrics. The main radiotherapy technique for this tumor type is craniospinal irradiation (CSI), through which the whole brain and spinal cord are exposed to radiation. Due to the immaturity of healthy organs in pediatrics, radiogenic side effects such as second cancer are more severe. Accordingly, the current study aimed to evaluate the risk of secondary cancer development in healthy organs following CSI. MATERIALS AND METHODS: Seven organs at risk (OARs) including skin, eye lens, thyroid, lung, liver, stomach, bladder, colon, and gonads were considered and the dose received by each OAR during CSI was measured inside an anthropomorphic RANDO phantom by TLDs. Then, the mean obtained dose for each organ was used to estimate the probability of secondary malignancy development according to the recommended cancer risk coefficients for specific organs. RESULTS: The results demonstrated that the stomach and colon are at high risk of secondary malignancy occurrence, while the skin has the lowest probability of secondary cancer development. The total received dose after the treatment course by all considered organs was lower than the corresponding tolerable dose levels. CONCLUSIONS: From the results, it can be concluded that some OARs during CSI are highly at risk of secondary cancer development. This issue may be of concern due to organ immaturity in pediatrics which can intensify the radiogenic effects of radiation exposure. Accordingly, strict shielding the OARs during craniospinal radiotherapy and/or sparing them from the radiation field through modern techniques such as hadron therapy is highly recommended.

Assessment of radiation exposure risks in patients undergoing elastic stable intramedullary nailing: Insights from intraoperative fluoroscopy.

INTRODUCTION: Elastic stable intramedullary nailing (ESIN) is a well-defined and appropriate treatment of choice for long bone fractures. Despite its benefits, the risk of cancer from imaging devices is of particular concern for younger adults. So, this survey was conducted to estimate the doses administered to patients undergoing ESIN of long bone fractures utilizing a 2-dimensional (2D) C-arm fluoroscopy machine during surgery, as well as the carcinogenic risk associated with the use of the machine. METHODS: This study was conducted on 147 patients who required ESIN for long-bone fractures. Patients' demographic data, surgical data and imaging information were collected. For each patient, the organ doses and the effective doses were computed with the Monte Carlo PCXMC 2.0 simulation software. The cancer risk models proposed in the Biological Effects of Ionizing Radiation VII (BEIR VII) Phase 2 report were used to evaluate the risk of exposure-induced cancer death (REID) values. RESULTS: For all patients, the highest organ dose was delivered to the gonads. The mean effective dose was 0.026 ± 0.015 mSv and 1.3E-04 ± 1E-04 mSv for ESIN of femur and tibia fractures, respectively. Males had a mean REID of 1 per million, while females had a mean REID of 0.19 per million. The younger males had considerably higher REID values. The effective dose was significantly correlated with age, gender, and irradiation time. CONCLUSION: Low levels of effective doses and cancer risks associated with the utilization of the fluoroscopy machine in current practice were found in ESIN treatment of long-bone fractures. IMPLICATIONS FOR PRACTICE: This outcome will help to raise surgeons' awareness of radiation risks and encourage them to initiate measures to keep radiation dose and exposure time as low as reasonably achievable.

Secondary cancer risk assessments following the proton therapy of lung cancer as the functions of field characteristics and patient age.

INTRODUCTION: Radiation-induced secondary cancers relevant to proton therapy are still a main concern among cancer survivors. This study aims to determine the effects of age at exposure and treatment field size on radiation-induced secondary tumors following the proton therapy of lung cancer within out of field organs through the Monte Carlo (MC) simulation approach. MATERIAL AND METHODS: A full MC model of ICRP-110 male phantom was simulated to calculate the absorbed dose corresponding to secondary radiations within distant organs from the tumor volume. Then, the risks of secondary malignancies were estimated by employing the recommended risk model by the Committee of Biological Effects of Ionizing Radiation (BEIR) for different treatment field sizes and various patient ages at exposure. RESULTS: The results revealed that by increasing the patient age from 25 to 45 years, lifetime attributable risk (LAR) values were decreased. Maximum and minimum mortality rates were obtained for the liver and thyroid at the fixed age of 25 years, respectively. Calculated risk values for most near organs to the tumor were higher than those for distant organs. Changing the aperture size from 5 × 5 cm2 to 8 × 10 cm2 resulted in LAR increments with maximum variations of 12.5% for the stomach and a rough variation of 1.12 times in LAR for all exposure ages. CONCLUSION: Our work on whole-body phantom addresses the impact of age at exposure and aperture size on LAR during the proton therapy of lung cancer. To minimize secondary cancer risks relevant to proton therapy of lung cancer, extra attention should be considered.

Third mortality follow-up of the Mallinckrodt uranium processing workers, 1942-2019.

INTRODUCTION: Mallinckrodt Chemical Works was a uranium processing facility during the Manhattan Project from 1942 to 1966. Thousands of workers were exposed to low-dose-rates of ionizing radiation from external and internal sources. This third follow-up of 2514 White male employees updates cancer and noncancer mortality potentially associated with radiation and silica dust. MATERIALS AND METHODS: Individual, annualized organ doses were estimated from film badge records (n monitored = 2514), occupational chest x-rays (n = 2514), uranium urinalysis (n = 1868), radium intake through radon breath measurements (n = 487), and radon ambient measurements (n = 1356). Silica dust exposure from pitchblende processing was estimated (n = 1317). Vital status and cause of death determination through 2019 relied upon the National Death Index and Social Security Administration Epidemiological Vital Status Service. The analysis included standardized mortality ratios (SMRs), Cox proportional hazards, and Poisson regression models. RESULTS: Vital status was confirmed for 99.4% of workers (84.0% deceased). For a dose weighting factor of 1 for intakes of uranium, radium, and radon decay products, the mean and median lung doses were 65.6 and 29.9 mGy, respectively. SMRs indicated a difference in health outcomes between salaried and hourly workers, and more brain cancer deaths than expected [SMR: 1.79; 95% confidence interval (CI): 1.14, 2.70]. No association was seen between radiation and lung cancer [hazard ratio (HR) at 100 mGy: 0.93; 95%CI: 0.78, 1.11]. The relationship between radiation and kidney cancer observed in the previous follow-up was maintained (HR at 100 mGy: 2.07; 95%CI: 1.12, 3.79). Cardiovascular disease (CVD) also increased significantly with heart dose (HR at 100 mGy: 1.11; 95%CI: 1.02, 1.21). Exposures to dust ≥23.6 mg/m3-year were associated with nonmalignant kidney disease (NMKD) (HR: 3.02; 95%CI: 1.12, 8.16) and kidney cancer combined with NMKD (HR: 2.46; 95%CI: 1.04, 5.81), though without evidence of a dose-response per 100 mg/m3-year. CONCLUSIONS: This third follow-up of Mallinckrodt uranium processors reinforced the results of the previous studies. There was an excess of brain cancers compared with the US population, although no radiation dose-response was detected. The association between radiation and kidney cancer remained, though potentially due to few cases at higher doses. The association between levels of silica dust ≥23.6 mg/m3-year and NMKD also remained. No association was observed between radiation and lung cancer. A positive dose-response was observed between radiation and CVD; however, this association may be confounded by smoking, which was unmeasured. Future work will pool these data with other uranium processing worker cohorts within the Million Person Study.

Application of multi-method-multi-model inference to radiation related solid cancer excess risks models for astronaut risk assessment.

The impact of including model-averaged excess radiation risks (ER) into a measure of radiation attributed decrease of survival (RADS) for the outcome all solid cancer incidence and the impact on the uncertainties is demonstrated. It is shown that RADS applying weighted model averaged ER based on AIC weights result in smaller risk estimates with narrower 95% CI than RADS using ER based on BIC weights. Further a multi-method-multi-model inference approach is introduced that allows calculating one general RADS estimate providing a weighted average risk estimate for a lunar and a Mars mission. For males the general RADS estimate is found to be 0.42% (95% CI: 0.38%; 0.45%) and for females 0.67% (95% CI: 0.59%; 0.75%) for a lunar mission and 2.45% (95% CI: 2.23%; 2.67%) for males and 3.91% (95% CI: 3.44%; 4.39%) for females for a Mars mission considering an age at exposure of 40 years and an attained age of 65 years. It is recommended to include these types of uncertainties and to include model-averaged excess risks in astronaut risk assessment.

Of Men and Mice: Using Terrestrial Radiation Epidemiology Methods to Inform Analysis of Animal Models for Space Radiation Risk Assessment.

Prediction of cancer risk from space radiation exposure is critical to ensure spaceflight crewmembers are adequately informed of the risks they face when accepting assignments to ambitious long-duration exploratory missions. Although epidemiological studies have assessed the effects of exposure to terrestrial radiation, no robust epidemiological studies of humans exposed to space radiation exist to support estimates of the risk from space radiation exposure. Mouse data derived from recent irradiation experiments provides valuable information to successfully develop mouse-based excess risks models for assessing relative biological effectiveness for heavy ions that can provide information to scale unique space radiation exposures so that excess risks estimated for terrestrial radiation can be adjusted for space radiation risk assessment. Bayesian analyses were used to simulate linear slopes for excess risk models with several different effect modifiers for attained age and sex. Relative biological effectiveness values for all-solid cancer mortality were calculated from the ratio of the heavy-ion linear slope to the gamma linear slope using the full posterior distribution and resulted in values that were substantially lower than what is currently applied in risk assessment. These analyses provide an opportunity to improve characterization of parameters used in the current NASA Space Cancer Risk (NSCR) model and generate new hypotheses for future animal experiments using out-bred mouse populations.

Assessment of cumulative cancer risk attributable to diagnostic X-ray radiation: a large cohort study.

OBJECTIVE: To assess the risk of cancer induced by diagnostic X-ray exposure in multiple radiological examinations and to explore the relevant influences to provide a reference for rational usage of X-ray examinations. METHODS: Data for all adult patients who underwent X-ray examinations from August 2004 to April 2020 in a general hospital was collected, including sex, age, primary diagnosis, and X-ray examination. Based on the Biological Effects of Ionizing Radiations report, age and sex and effective dose for a single X-ray examination were used to calculate the lifetime attributable risk (LAR). Patients whose cancer LAR values were in the top 5% were considered to have a high cancer risk; the factors influencing this status were explored by using multivariate logistic regression analyses. RESULTS: In total, 1,143,413 patients with 3,301,286 X-ray examinations were included. LARs of cancer incidence and death were < 0.2% and < 0.13% among 95% of patients and they were > 1% among 0.21% and 0.07% of patients. High risks of incidence and death were significantly associated with corrected exposure frequency (odds ratio [OR], 1.080 and 1.080), sex (OR, male vs. female, 0.421 and 0.372), and year of birth (OR, 1.088 and 1.054), with all p values < 0.001. Among 20 disease categories, congenital disease (OR, 3.792 and 4.024), genitourinary disease (OR, 3.608 and 3.202), digestive disease (OR, 3.247 and 3.272), and tumor disease (OR, 2.706 and 2.767) had the strongest associations with high risks of incidence and death (all p values < 0.001). CONCLUSIONS: Cancer risk induced by diagnostic X-ray examinations can be considered acceptable clinically. Patients having certain diseases are potentially at a relative higher risk due to recurrent examinations. KEY POINTS: • It was the first large-scale investigation of cumulative X-ray exposure in China, involving more than 3.3 million X-ray scans of all types of diagnostic X-ray examinations for about 1.1 million patients during the past 16 years. • The study revealed that the incidence risk of cancer induced by X-ray-related examinations was 0.01% on average, which was substantially lower than that of cancer induced by non-X-ray radiation. The risk could be considered acceptable clinically. • Patients having certain diseases were potentially at a relatively higher cancer risk due to recurrent X-ray examinations. The cumulative effect of X-ray exposure could not be ignored and was worthy of attention.

Demonstrating the undermining of science and health policy after the Fukushima nuclear accident by applying the Toolkit for detecting misused epidemiological methods.

It is well known that science can be misused to hinder the resolution (i.e., the elimination and/or control) of a health problem. To recognize distorted and misapplied epidemiological science, a 33-item "Toolkit for detecting misused epidemiological methods" (hereinafter, the Toolkit) was published in 2021. Applying the Toolkit, we critically evaluated a review paper entitled, "Lessons learned from Chernobyl and Fukushima on thyroid cancer screening and recommendations in the case of a future nuclear accident" in Environment International in 2021, published by the SHAMISEN (Nuclear Emergency Situations - Improvement of Medical and Health Surveillance) international expert consortium. The article highlighted the claim that overdiagnosis of childhood thyroid cancers greatly increased the number of cases detected in ultrasound thyroid screening following the 2011 Fukushima nuclear accident. However, the reasons cited in the SHAMISEN review paper for overdiagnosis in mass screening lacked important information about the high incidence of thyroid cancers after the accident. The SHAMISEN review paper ignored published studies of screening results in unexposed areas, and included an invalid comparison of screenings among children with screenings among adults. The review omitted the actual state of screening in Fukushima after the nuclear accident, in which only nodules > 5 mm in diameter were examined. The growth rate of thyroid cancers was not slow, as emphasized in the SHAMISEN review paper; evidence shows that cancers detected in second-round screening grew to more than 5 mm in diameter over a 2-year period. The SHAMISEN consortium used an unfounded overdiagnosis hypothesis and misguided evidence to refute that the excess incidence of thyroid cancer was attributable to the nuclear accident, despite the findings of ongoing ultrasound screening for thyroid cancer in Fukushima and around Chernobyl. By our evaluation, the SHAMISEN review paper includes 20 of the 33 items in the Toolkit that demonstrate the misuse of epidemiology. The International Agency for Research on Cancer meeting in 2017 and its publication cited in the SHAMISEN review paper includes 12 of the 33 items in the Toolkit. Finally, we recommend a few enhancements to the Toolkit to increase its utility.

Ethical challenges of the linear non-threshold (LNT) cancer risk assessment revolution: History, insights, and lessons to be learned.

This paper provides historical review and evaluation of the development, adoption, and advocacy of the linear non-threshold (LNT) dose response model for cancer risk assessment as applied in practices and policies worldwide. It extends previous historical assessments and provides novel insights regarding: 1) how LNT bias became institutionalized in US governmental agencies, 2) how improper editorial practices at the journal Science promoted the adoption of LNT, 3) how a Nobel Prize winning scientist unjustifiably espoused and influenced support for replacing the threshold dose response model with the LNT model, 4) how the cover-up of striking and substantial experimental cancer data by US government scientists reduced support for the threshold dose response model at a critical period of cancer risk assessment policy adoption, and 5) how these events have negatively influenced cancer risk assessment practices and environmental and public health decisions for decades. These findings are presented to illustrate how profound and recognized mistakes, biases and unethical activities, inclusive of frank scientific misconduct, converged, and should motivate regulatory agencies worldwide to critically evaluate any existing policies that apply the LNT model as well as to serve as object lessons for current and future ethical conduct of research, and the provision of ethico-legal education in and across scientific curricula and institutions.

Cover up and cancer risk assessment: Prominent US scientists suppressed evidence to promote adoption of LNT.

This paper reports that William Russell, Oak Ridge National Laboratory (ORNL), conducted a large-scale lifetime study from 1956 to 1959 showing that exposure of young adult male mice to a large dose of acute X-rays had no treatment effects on male and female offspring concerning longevity or the frequency, severity, or age distribution of neoplasms and other diseases. Despite the scientific, societal and crucial timing significance of the study, Russell did not publish the findings for almost 35 years, nor did he inform governmental advisory committees, thereby significantly biasing decisions made during this period which supported the adoption of LNT for risk assessment. Of further significance, Arthur Upton, an ORNL colleague of Russell during this study and later Director of the US National Cancer Institute (NCI), was also fully knowledgeable of this study, its findings and its negative impact on the acceptance of LNT. Upton later worked along with Russell to publish these data (i.e., Cosgrove et al., 1993) to dispute the case-specific claim that children developed cancer because of the radiation exposure of their fathers as workers at the Sellafield nuclear plant. Thus, while Russell's data were available, but were not used to challenge the key radiation and leukemia paper of Edward B. Lewis, (1957) when LNT was being adopted by regulatory agencies, they were used in a major trial in the United Kingdom (UK) for the client (i.e., British Nuclear Fuels Plc) that hired Upton. While the duplicity of Russell's and Upton's actions is striking, the key finding of the present paper is that Russell and Upton intentionally orchestrated and sustained an LNT cover up during the key period of LNT adoption by regulatory agencies, thereby showing an overwhelming bias to enhance the adoption of LNT.

Impact of uncertainties in exposure assessment on thyroid cancer risk among cleanup workers in Ukraine exposed due to the Chornobyl accident.

A large excess risk of thyroid cancer was observed among Belarusian/Russian/Baltic Chornobyl cleanup workers. A more recent study of Ukraine cleanup workers found more modest excess risks of thyroid cancer. Dose errors in this data are substantial, associated with model uncertainties and questionnaire response. Regression calibration is often used for dose-error adjustment, but may not adequately account for the full error distribution. We aimed to examine the impact of exposure-assessment uncertainties on thyroid cancer among Ukrainian cleanup workers using Monte Carlo maximum likelihood, and compare with results derived using regression calibration. Analyses assessed the sensitivity of results to various components of internal and external dose. Regression calibration yielded an excess odds ratio per Gy (EOR/Gy) of 0.437 (95% CI - 0.042, 1.577, p = 0.100), compared with the EOR/Gy using Monte Carlo maximum likelihood of 0.517 (95% CI - 0.039, 2.035, p = 0.093). Trend risk estimates for follicular morphology tumors exhibited much more extreme effects of full-likelihood adjustment, the EOR/Gy using regression calibration of 3.224 (95% CI - 0.082, 30.615, p = 0.068) becoming ~ 50% larger, 4.708 (95% CI - 0.075, 85.143, p = 0.066) when using Monte Carlo maximum likelihood. Results were sensitive to omission of external components of dose. In summary, use of Monte Carlo maximum likelihood adjustment for dose error led to increases in trend risks, particularly for follicular morphology thyroid cancers, where risks increased by ~ 50%, and were borderline significant. The unexpected finding for follicular tumors needs to be replicated in other exposed groups.

Monte Carlo study of organ doses and related risk for cancer in Algeria from scattered neutrons in prostate treatment involving 3D-CRT.

The present study aimed to evaluate organ doses and related risk for cancer from scattered neutrons involving 3D Conformational Radiotherapy (3D-CRT) for patients with prostate cancer in Algeria based on Monte Carlo technique and to estimate the secondary cancer risks. To this purpose, a detailed geometric Monte Carlo (MC) modeling of the LINAC Varian 2100C combined with a computational whole-body phantom was carried out. The neutron equivalent doses were calculated in-field and out-of field of patient's organs using the phase-space method. The obtained neutron equivalent doses were used to estimate the Lifetime Attributable Risks (LARs) for cancer incidence in out of field organs. LARs was evaluated assuming Biological Effects of Ionizing Radiation VII (BEIR VII) risk model for exposure age in the range 35-70 years, according to the interval's age of treated patients in Algeria. The baselines cancer risks and survival data were associated with the statistical data for the Algerian population. The results showed that the neutrons equivalent doses per prescribed dose (Photon Dose) mostly depend on the distance of organs from the treated volume. The highest and lowest equivalent doses of 1.18 mSv/Gy and 0.25 mSv/Gy were recorded in the bladder and heart, respectively. The highest estimated lifetime attributable risk per 100,000 population was found for 35 yrs' exposure age in colon 49.94, lung 16.63 and stomach 11.17. The lowest risks were found for 70 yrs' age, in spine 0.06 and thyroid 0.14. The results showed that LARs values decrease with the increase of the exposure age and cancer incidence risk is lower than the baseline cancer risk incidence for all organs. The present study may help in providing a database on the impact of radiotherapy-induced secondary cancer incidence during 3D-CRT for prostate cancer in Algeria.

Mortality among workers at the Los Alamos National Laboratory, 1943-2017.

BACKGROUND: During World War II (WWII), the Manhattan Engineering District established a secret laboratory in the mountains of northern New Mexico. The mission was to design, construct and test the first atomic weapon, nicknamed 'The Gadget' that was detonated at the TRINITY site in Alamogordo, NM. After WWII, nuclear weapons research continued, and the laboratory became the Los Alamos National Laboratory (LANL). MATERIALS AND METHODS: The mortality experience of 26,328 workers first employed between 1943 and 1980 at LANL was determined through 2017. Included were 6157 contract workers employed by the ZIA Company. Organ dose estimates for each worker considered all sources of exposure, notably photons, neutrons, tritium, 238Pu and 239Pu. Vital status determination included searches within the National Death Index, Social Security Administration and New Mexico State Mortality Files. Standardized Mortality Ratios (SMR) and Cox regression models were used in the analyses. RESULTS: Most workers (55%) were hired before 1960, 38% had a college degree, 25% were female, 81% white, 13% Hispanic and 60% had died. Vital status was complete, with only 0.1% lost to follow-up. The mean dose to the lung for the 17,053 workers monitored for radiation was 28.6 weighted-mGy (maximum 16.8 weighted-Gy) assuming a Dose Weighting Factor of 20 for alpha particle dose to lung. The Excess Relative Risk (ERR) at 100 weighted-mGy was 0.01 (95%CI -0.02, 0.03; n = 839) for lung cancer. The ERR at 100 mGy was -0.43 (95%CI -1.11, 0.24; n = 160) for leukemia other than chronic lymphocytic leukemia (CLL), -0.06 (95%CI -0.16, 0.04; n = 3043) for ischemic heart disease (IHD), and 0.29 (95%CI 0.02, 0.55; n = 106) for esophageal cancer. Among the 6499 workers with measurable intakes of plutonium, an increase in bone cancer (SMR 2.44; 95%CI 0.98, 5.03; n = 7) was related to dose. The SMR for berylliosis was significantly high, based on 4 deaths. SMRs for Hispanic workers were significantly high for cancers of the stomach and liver, cirrhosis of the liver, nonmalignant kidney disease and diabetes, but the excesses were not related to radiation dose. CONCLUSIONS: There was little evidence that radiation increased the risk of lung cancer or leukemia. Esophageal cancer was associated with radiation, and plutonium intakes were linked to an increase of bone cancer. IHD was not associated with radiation dose. More precise evaluations will await the pooled analysis of workers with similar exposures such as at Rocky Flats, Savannah River and Hanford.

Secondary neutron dose contribution from pencil beam scanning, scattered and spatially fractionated proton therapy.

The Orsay Proton therapy Center (ICPO) has a long history of intracranial radiotherapy using both double scattering (DS) and pencil beam scanning (PBS) techniques, and is actively investigating a promising modality of spatially fractionated radiotherapy using proton minibeams (pMBRT). This work provides a comprehensive comparison of the organ-specific secondary neutron dose due to each of these treatment modalities, assessed using Monte Carlo (MC) algorithms and measurements. A MC model of a universal nozzle was benchmarked by comparing the neutron ambient dose equivalent,H*(10), in the gantry room with measurements obtained using a WENDI-II counter. The secondary neutron dose was evaluated for clinically relevant intracranial treatments of patients of different ages, in which secondary neutron doses were scored in anthropomorphic phantoms merged with the patients' images. The MC calculatedH*(10) values showed a reasonable agreement with the measurements and followed the expected tendency, in which PBS yields the lowest dose, followed by pMBRT and DS. Our results for intracranial treatments show that pMBRT yielded a higher secondary neutron dose for organs closer to the target volume, while organs situated furthest from the target volume received a greater quantity of neutrons from the passive scattering beam line. To the best of our knowledge, this is the first study to compare MC secondary neutron dose estimates in clinical treatments between these various proton therapy modalities and to realistically quantify the secondary neutron dose contribution of clinical pMBRT treatments. The method established in this study will enable epidemiological studies of the long-term effects of intracranial treatments at ICPO, notably radiation-induced second malignancies.

Racial differences in the risk of second primary bladder cancer following radiation therapy among localized prostate cancer patients.

OBJECTIVES: To investigate the race-specific second primary bladder cancer (SPBC) risk following prostatic irradiation. METHODS: Louisiana residents who were diagnosed with localized prostate cancer (PCa) in 1996-2013 and received surgery or radiation were included. Patients were followed until SPBC diagnosis, death, or Dec. 2018. The exposure variable was type of treatment (radiation only vs. surgery only). The outcome was time from PCa diagnosis to SPBC diagnosis, stratified by race. Fine and Gray's competing risk model was applied with death as a competing event and adjustment of sociodemographic and tumor characteristics. We used 5 years and 10 years as lag time in the analyses. RESULTS: A total of 26,277 PCa patients with a median follow-up of 10.7 years were analyzed, including 18,598 white and 7679 black patients. About 42.9 % of whites and 45.7 % of blacks received radiation. SPBC counted for 1.84 % in the radiation group and 0.90 % in the surgery group among white patients and for 0.91 % and 0.58 %, respectively, among black patients. The adjusted subdistribution hazard ratio of SPBC was 1.80 (95 % CI: 1.30-2.48) for radiation recipients compared to surgery recipients among white patients; 1.93 (95 % CI: 1.36-2.74) if restricted to external beam radiation therapy (EBRT). The SPBC risk was not significantly different between irradiated and surgically treated among blacks. CONCLUSIONS: The SPBC risk is almost two-fold among white irradiated PCa patients compared to their counterparts treated surgically. Our findings highlight the need for enhanced surveillance for white PCa survivors receiving radiotherapy, especially those received EBRT.

Development of clinical application program for radiotherapy induced cancer risk calculation using Monte Carlo engine in volumetric-modulated arc therapy.

BACKGROUND: The purpose of this study is to develop a clinical application program that automatically calculates the effect for secondary cancer risk (SCR) of individual patient. The program was designed based on accurate dose calculations using patient computed tomography (CT) data and Monte Carlo engine. Automated patient-specific evaluation program was configured to calculate SCR. METHODS: The application program is designed to re-calculate the beam sequence of treatment plan using the Monte Carlo engine and patient CT data, so it is possible to accurately calculate and evaluate scatter and leakage radiation, difficult to calculate in TPS. The Monte Carlo dose calculation system was performed through stoichiometric calibration using patient CT data. The automatic SCR evaluation program in application program created with a MATLAB was set to analyze the results to calculate SCR. The SCR for organ of patient was calculated based on Biological Effects of Ionizing Radiation (BEIR) VII models. The program is designed to sequentially calculate organ equivalent dose (OED), excess absolute risk (EAR), excess relative risk (ERR), and the lifetime attributable risk (LAR) in consideration of 3D dose distribution analysis. In order to confirm the usefulness of the developed clinical application program, the result values from clinical application program were compared with the manual calculation method used in the previous study. RESULTS: The OED values calculated in program were calculated to be at most approximately 13.3% higher than results in TPS. The SCR result calculated by the developed clinical application program showed a maximum difference of 1.24% compared to the result of the conventional manual calculation method. And it was confirmed that EAR, ERR and LAR values can be easily calculated by changing the biological parameters. CONCLUSIONS: We have developed a patient-specific SCR evaluation program that can be used conveniently in the clinic. The program consists of a Monte Carlo dose calculation system for accurate calculation of scatter and leakage radiation and a patient-specific automatic SCR evaluation program using 3D dose distribution. The clinical application program that improved the disadvantages of the existing process can be used as an index for evaluating a patient treatment plan.

A bespoke health risk assessment methodology for the radiation protection of astronauts.

An alternative approach that is particularly suitable for the radiation health risk assessment (HRA) of astronauts is presented. The quantity, Radiation Attributed Decrease of Survival (RADS), representing the cumulative decrease in the unknown survival curve at a certain attained age, due to the radiation exposure at an earlier age, forms the basis for this alternative approach. Results are provided for all solid cancer plus leukemia incidence RADS from estimated doses from theoretical radiation exposures accumulated during long-term missions to the Moon or Mars. For example, it is shown that a 1000-day Mars exploration mission with a hypothetical mission effective dose of 1.07 Sv at typical astronaut ages around 40 years old, will result in the probability of surviving free of all types of solid cancer and leukemia until retirement age (65 years) being reduced by 4.2% (95% CI 3.2; 5.3) for males and 5.8% (95% CI 4.8; 7.0) for females. RADS dose-responses are given, for the outcomes for incidence of all solid cancer, leukemia, lung and female breast cancer. Results showing how RADS varies with age at exposure, attained age and other factors are also presented. The advantages of this alternative approach, over currently applied methodologies for the long-term radiation protection of astronauts after mission exposures, are presented with example calculations applicable to European astronaut occupational HRA. Some tentative suggestions for new types of occupational risk limits for space missions are given while acknowledging that the setting of astronaut radiation-related risk limits will ultimately be decided by the Space Agencies. Suggestions are provided for further work which builds on and extends this new HRA approach, e.g., by eventually including non-cancer effects and detailed space dosimetry.

LNT and cancer risk assessment: Its flawed foundations part 2: How unsound LNT science became accepted.

This paper argues that Edward B. Lewis served as a type of independent academic radiation LNT-cancer risk assessment-stalking horse for the BEAR Genetics Panel, a task for which he had no expertise or experience (e.g. radiation, leukemia, epidemiology and statistical modelling). His efforts produced an insufficiently documented, strongly biased, and high-profile paper in Science (May 17, 1957), whose principal conclusions had not been proven, he asserted privately, in writing. This inconclusive perspective was well camouflaged in the published paper by means of sophisticated wordsmithing. At the time his academic department head George Beadle came to chair the BEAR Genetics Panel in the summer of 1956, the Beadle-inspired-Lewis LNT activity acquired an urgency when a study of 70,000 offspring from survivors of the A-bombs failed to show genetic damage after a decade of careful study, undercutting Panel recommendations. With Beadle's guidance, the Lewis effort redirected the Panel's focus from the atomic bomb genetic damage study, which had acrimoniously disrupted Panel relationships and priorities, to more immediate disciplinary/professional opportunities with concerns about fallout, leukemia risks and a new cancer causation role for mutation. The serious limitations of the Lewis paper affected neither its publication in Science nor its receiving an editorial endorsement, possibly due to influence by powerful Panel members, such as Bentley Glass, one of only six senior editors for Science. The Science publication restored, even though improperly, the scientific and moral initiatives of the Panel and led directly to multiple high level LNT recommendations for cancer risk assessment based on the Precautionary Principle, which Lewis asserted, and which remains in place today in essentially all countries. The present paper explores how such a scientific long-shot and quasi-stalking horse, who was unsupported by BEAR Panel members during the withering criticism prompted by his Science article, nevertheless endured in the pursuit of his LNT goal, becoming strikingly successful in achieving a global cancer risk assessment revolution which remains in place.

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.

Young Adult Populations Face Yet Another Barrier to Care With Insurers: Limited Access to Proton Therapy.

PURPOSE: Young patients, including pediatric, adolescent, and young adult (YA) patients, are most likely to benefit from the reduced integral dose of proton beam radiation therapy (PBT) resulting in fewer late toxicities and secondary malignancies. This study sought to examine insurance approval and appeal outcomes for PBT among YA patients compared with pediatric patients at a large-volume proton therapy center. METHODS AND MATERIALS: We performed a cross-sectional cohort study of 284 consecutive patients aged 0 to 39 years for whom PBT was recommended in 2018 through 2019. Pediatric patients were defined as aged 0 to 18 years and YA patients 19 to 39 years. Rates of approval, denials, and decision timelines were calculated. Tumor type and location were also evaluated as factors that may influence insurance decisions. RESULTS: A total of 207 patients (73%) were approved for PBT at initial request. YA patients (n = 68/143, 48%) were significantly less likely to receive initial approval compared with pediatric patients (n = 139/141; 99%) (P < .001). Even after 47% (n = 35 of 75) of the PBT denials for YA patients were overturned, YAs had a significantly lower final PBT approval (72% vs pediatric 99%; P < .001). The median wait time was also significantly longer for YA patients (median, 8 days; interquartile range [IQR] 3-17 vs median, 2 days; IQR, 0-6; P < .001). In those patients requiring an appeal, the median wait time was 16 days (IQR, 9-25). CONCLUSION: Given the decades of survivorship of YA patients, PBT is an important tool to reduce late toxicities and secondary malignancies. Compared with pediatric patients, YA patients are significantly less likely to receive insurance approval for PBT. Insurance denials and subsequent appeal requests result in significant delays for YA patients. Insurers need to re-examine their policies to include expedited decisions and appeals and removal of arbitrary age cutoffs so that YA patients can gain easier access to PBT. Furthermore, consensus guidelines encouraging greater PBT access for YA may be warranted from both medical societies and/or AYA experts.