Lung Cancer Risk Estimates Research Articles

Cancer mortality risk in the Urals Cohort of Exposed Population Offspring

The objective of the study is to analyze solid cancer mortality and estimate the risk value of solid cancer mortality in the offspring of parents irradiated in the Southern Urals, depending on the dose to the parents' gonads as well as to conduct a preliminary assessment of the mortality risk from cancer of individual locations depending on the gonadal dose. The issue of the transgenerational effects of the human gonad exposure is still very important. There exists conclusive evidence of the presence of such effects in experimental animals. However, there is no proof of the existence of these effects in humans despite a great number of research on this subject. International scientific community and international organizations, UNSCEAR and ICRP being among them, regard this issue as the one that has not been solved yet and requires further studies. Urals Cohort of offspring of the population exposed on the Techa River and on the territory of the East Ural radioactive trace was established in the Urals research Center for Radiation medicine in 2022. The key feature of the cohort is the exclusion of the offspring with postnatal exposure. The size of the cohort as of September 2023 is 31,154 persons. The number of person-years over the whole follow-up period from 1950 through 2020 is 1 226 380. Mean dose to the gonads of mothers of all the cohort members is 41 mGy, to those of the fathers' — 35 mGy, mean combined gonad dose is 76 mGy. Over the whole follow-up period 3,774 deaths from all causes including 284 deaths from solid cancers were registered in the cohort. The mean age of the cohort members at the end of the follow-up period was 42 years. The risk of death was analyzed using Poisson regression by the programs of the EPICURE statistical software package. Three models of dose dependence were tested: linear, quadratic, and linear-quadratic models of paternal gonadal dose, maternal gonadal dose, and total gonadal dose. Mortality risk analysis of all solid cancers in the offspring cohort showed no statistically significant effect with parental gonadal dose (we have obtained positive although statistically insignificant values of solid cancers mortality risk) which is consistent with the results of other studies in human populations. At the same time, the analysis for the first time obtained a statistically significant linear dependence of the solid cancer mortality risk in offspring with father's age over 45 years depending on the dose to the father's gonads. The excess relative risk of death was 8.09/Gy, (0.51-22.93), p < 0.05. Also, for the first time, evidence of dose dependence of the mortality risk of lung cancer in male offspring on maternal gonadal dose, paternal gonadal dose, and combined gonadal dose was obtained. The values of excess relative risk of lung cancer and 95% confidence intervals according to the linear model were 5.39/Gy (0.46; 15.56) from paternal gonad dose, 4.36/Gy (0.15; 13.48) from maternal gonad dose, and - 3.95/Gy (0.55; 12.14) from combined gonad dose. Point risk estimates of lung cancer at this stage are characterized by wide confidence intervals and require additional studies to assess the influence of possible effect modifiers, but with a high degree of probability indicate the presence of dose dependence of this effect. Increasing the follow-up period and attained age, will increase the number of cancers in the future and will reduce dose response uncertainties and provide more accurate estimates of the risk of death in the offspring cohort.

Estimation of radon annual effective dose and excess lung cancer risk for the residents of KufrKhal, Jordan

This study aims to measure radon gas concentration, calculate the annual effective dose, and calculate excess lung cancer risk in KufrKhal-Jerash north of Jordan. Radon is a radioactive gas located everywhere and contributes more than 40% of people’s total dose from natural radiation. The Risk concerns have resulted from the increase in mortality due to lung cancer in KufrKhal. About 117 well-calibrated dosimeters were among the study area’s districts (Hill 1, Hill 2, Hill 3, and village center). Each dosimeter consists of a plastic cup with known dimensions and a piece of solid state nuclear track detector (SSNTD) type CR-39 fixed in the inner bottom of the cup. After 90 days, the retrieved detectors were chemically etched, and the track density (tracks.cm−2) was determined. The results showed that the average radon concentrations drastically varied between the districts of KufrKhal (17.1–128.8 Bqm−3). However, the mean radon values in different districts are closely related (64.4–75.5 Bq.m−3). The lowest concentration (17.1 Bqm−3) was found in the Hill 1 district, and the highest value (128.8 Bqm−3) was found in the village center. However, the overall radon concentration in KufrKhal was approximately 69.2 Bqm−3. This value is within the range of the national average level (43.2 – 77.4 Bq.m−3) and way below the national action level (200 Bq.m−3). Furthermore, the corresponding values of the annual effective dose (AED) and the excess lung cancer risk (ELCR) for dwellers in this village were calculated to be 1.8 mSv.y−1 and 0.2%, respectively. These values, according to Jordan’s national regulations are acceptable.

Association between Serum 6:2 Chlorinated Polyfluorinated Ether Sulfonate Concentrations and Lung Cancer.

6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibits pronounced estrogenic effects, potentially influencing the etiology of lung cancer. This study assessed the potential associations between serum concentrations of 6:2 Cl-PFESA and lung cancer risk at the population level. Odds ratios (ORs) for lung cancer across serum 6:2 Cl-PFESA quartiles were assessed using conditional logistic regression. Additionally, we investigated potential effect modification by various confounding factors. Elevated serum levels of 6:2 Cl-PFESA were consistently associated with an increased risk of lung cancer in both the crude model (OR = 1.62, 95% CI: 1.08-2.42, p = 0.018) and the adjusted model (OR = 1.59, 95% CI: 1.06-2.39, p = 0.026). Stratified analyses revealed that elevated serum levels of 6:2 Cl-PFESA were associated with increased risk estimates of lung cancer among males (adjusted OR = 2.04, 95% CI: 1.19-3.51, p = 0.006), smokers (adjusted OR = 2.48, 95% CI: 1.25-4.89, p = 0.003), and drinkers (adjusted OR = 2.20, 95% CI: 0.94-5.16, p = 0.049). The results of this study imply that exposure to 6:2 Cl-PFESA at levels considered environmentally relevant may be linked to an elevated risk of developing lung cancer.

The Use of a Tailored Decision Aid to Improve Understanding of Lung Cancer Screening in People With HIV

People with HIV are at increased risk for lung cancer and multimorbidity, complicating the balance of risks and benefits of lung cancer screening. We previously adapted Decision Precision (screenlc.com) to guide shared decision-making for lung cancer screening in people with HIV. Does an HIV-adapted and personally tailored decision aid improve shared decision-making regarding lung cancer screening in people with HIV as measured by knowledge, decisional conflict, and acceptability? This was a single-arm pilot trial of the decision aid in 40 participants with HIV eligible for lung cancer screening. The decision aid included personalized screening recommendations and HIV-specific, five-year risk estimates of lung cancer and all-cause mortality. Participants reviewed the decision aid at shared decision-making visits and completed pre- and post-visit surveys with measures of knowledge about lung cancer screening, acceptability, and decisional conflict. The 40 enrolled participants were a median 62 years old and 60% were currently smoking with median five-year risks of lung cancer and all-cause mortality of 2.0% (IQR 1.4-3.3%) and 4.1% (IQR 3.3-7.9%). Personalized recommendations included "Encourage Screening" for 53% of participants and "Preference Sensitive" recommendations for the remainder. Participants showed improvement in two validated knowledge measures with relative improvement of 60% (p<0.001) on the LCS-12 and 27% (p<0.001) on the LKS-7, with significant improvement on questions regarding false-positive and false-negative findings, incidental findings, lung cancer-specific mortality benefit, and the possible harms of screening. Participants reported low scores on the decisional conflict scale (median score 0, IQR 0-5) and high acceptability. Ninety percent ultimately underwent screening within one month of the visit. This HIV-adapted and personally tailored decision aid improved participants' knowledge of risks, benefits, and characteristics of screening with low decisional conflict and high acceptability. This decision aid can enable high-quality shared decision-making in this high-risk population.

Histology-specific standardized incidence ratio improves the estimation of second primary lung cancer risk

BackgroundLung cancer (LC) survivors are at increased risk for developing a second primary cancer (SPC) compared to the general population. While this risk is particularly high for smoking-related SPCs, the published standardized incidence ratio (SIR) for lung cancer after lung cancer is unexpectedly low in countries that follow international multiple primary (IARC/IACR MP) rules when compared to the USA, where distinct rules are employed. IARC/IACR rules rely on histology-dependent documentation of SPC with the same location as the first cancer and only classify an SPC when tumors present different histology. Thus, SIR might be underestimated in cancer registries using these rules. This study aims to assess whether using histology-specific reference rates for calculating SIR improves risk estimates for second primary lung cancer (SPLC) in LC survivors.MethodsWe (i) use the distribution of histologic subtypes of LC in population-based cancer registry data of 11 regional cancer registries from Germany to present evidence that the conventional SIR metric underestimates the actual risk for SPLC in LC survivors in registries that use IARC/IACR MP rules, (ii) present updated risk estimates for SPLC in Germany using a novel method to calculate histological subtype-specific SIRs, and (iii) validate this new method using US SEER (Surveillance, Epidemiology, and End Results Program) data, where different MP rules are applied.ResultsThe adjusted relative risk for lung cancer survivors in Germany to develop an SPLC was 2.98 (95% CI 2.53–3.49) for females and 1.15 (95% CI 1.03–1.27) for males using the novel histology-specific SIR. When using IARC/IACR MP rules, the conventional SIR underestimates the actual risk for SPLC in LC survivors by approximately 30% for both sexes.ConclusionsOur proposed histology-specific method makes the SIR metric more robust against MP rules and, thus, more suitable for cross-country comparisons.

Prevalent occupational exposures and risk of lung cancer among women: Results from the application of the Canadian Job-Exposure Matrix (CANJEM) to a combined set of ten case-control studies.

Worldwide, lung cancer is the second leading cause of cancer death in women. The present study explored associations between occupational exposures that are prevalent among women, and lung cancer. Data from 10 case-control studies of lung cancer from Europe, Canada, and New Zealand conducted between 1988 and 2008 were combined. Lifetime occupational history and information on nonoccupational factors including smoking were available for 3040 incident lung cancer cases and 4187 controls. We linked each reported job to the Canadian Job-Exposure Matrix (CANJEM), which provided estimates of probability, intensity, and frequency of exposure to each selected agent in each job. For this analysis, we selected 15 agents (cleaning agents, biocides, cotton dust, synthetic fibers, formaldehyde, cooking fumes, organic solvents, cellulose, polycyclic aromatic hydrocarbons from petroleum, ammonia, metallic dust, alkanes C18+, iron compounds, isopropanol, and calcium carbonate) that had lifetime exposure prevalence of at least 5% in the combined study population. For each agent, we estimated lung cancer risk in each study center for ever-exposure, by duration of exposure, and by cumulative exposure, using separate logistic regression models adjusted for smoking and other covariates. We then estimated the meta-odds ratios using random-effects meta-analysis. None of the agents assessed showed consistent and compelling associations with lung cancer among women. The following agents showed elevated odds ratio in some analyses: metallic dust, iron compounds, isopropanol, and organic solvents. Future research into occupational lung cancer risk factors among women should prioritize these agents.

Using particle dimensionality-based modeling to estimate lung carcinogenicity of 3D printer emissions.

The use of 3D printing technologies by industry and consumers is expanding. However, the approaches to assess the risk of lung carcinogenesis from the emissions of 3D printers have not yet been developed. The objective of the study was to demonstrate a methodology for modeling lung cancer risk related to specific exposure levels as derived from an experimental study of 3D printer emissions for various types of filaments (ABS, PLA, and PETG). The emissions of 15 filaments were assessed at varying extrusion temperatures for a total of 23 conditions in a Class 1,000 cleanroom following procedures described by ANSI/CAN/UL 2904. Three approaches were utilized for cancer risk estimation: (a) calculation based on PM2.5 and PM10 concentrations, (b) a proximity assessment based on the pulmonary deposition fraction, and (c) modeling based on the mass-weighted aerodynamic diameter of particles. The combined distribution of emitted particles had the mass median aerodynamic diameter (MMAD) of 0.35 μm, GSD 2.25. The average concentration of PM2.5 was 25.21 μg/m3 . The spline-based function of aerodynamic diameter allowed us to reconstruct the carcinogenic potential of seven types of fine and ultrafine particles (crystalline silica, fine TiO2 , ultrafine TiO2 , ambient PM2.5 and PM10, diesel particulates, and carbon nanotubes) with a correlation of 0.999, P < 0.00001. The central tendency estimation of lung cancer risk for 3D printer emissions was found at the level of 14.74 cases per 10,000 workers in a typical exposure scenario (average cumulative exposure of 0.3 mg/m3 - years), with the lowest risks for PLA filaments, and the highest for PETG type.

Mortality benefit of a blood-based biomarker panel for lung cancer and the PLCO cohort.

8560 Background: A 4-protein biomarker panel (4MP) combined with the validated PLCOm2012 clinical risk model has been shown to improve lung cancer risk estimation over either metric alone. We investigated whether these panels in combination could also identify individuals at high risk of harboring a lethal lung cancer. Methods: We used data from an established logistic regression combining the 4MP and the PLCOm2012 risk model, which were assessed in pre-diagnostic sera from 552 lung cancer cases and 2,193 non-cases from the Prostate Lung Colorectal and Ovarian (PLCO) cohort. Of the 552 lung cancer cases, 387 (70%) died from lung cancer. Cumulative incidence of lung cancer death as well as sub-distributional and cause-specific hazard ratios were calculated based on 4MP+PLCOm2012 risk scores at a pre-defined 1.0% and 1.7% 6-year risk thresholds, which correspond to the 2013 and 2021 US Preventive Services Task Force lung cancer screening criteria, respectively. Results: When considering cases diagnosed within 1 year of blood draw and all non-cases, the AUC estimate of the 4MP+PLCOm2012 model for risk prediction of lung cancer death was 0.88 (95% CI: 0.86-0.90). Among cases, the cumulative incidence of lung cancer death was statistically significantly higher in individuals with 4MP+PLCOm2012 scores above the 1.0% 6-year risk threshold (modified χ2: 5.42, P: 0.02). Corresponding sub-distributional and lung cancer death-specific hazard ratios for test-positive cases were 1.69 (95% CI: 1.07-2.66) and 1.80 (95% CI: 1.15-2.82), respectively. Conclusions: The blood-based biomarker panel in combination with PLCOm2012 identifies individuals at high risk of a lethal lung cancer.

What Can Current Biomarker Data Tell Us About the Risks of Lung Cancer Posed by Heated Tobacco Products?

Heated tobacco products (HTPs) are marketed as less harmful alternatives to cigarettes, but the lung cancer risk of HTPs is unknown. In the absence of epidemiological data, assessing the risks of HTPs relies on biomarker data from clinical trials. This study examined existing biomarker data to determine what it tells us about the lung cancer risk posed by HTPs. We identified all biomarkers of exposure and potential harm measured in HTP trials and evaluated their appropriateness based on ideal characteristics for measuring lung cancer risk and tobacco use. The effects of HTPs on the most appropriate biomarkers within cigarette smokers switched to HTPs and compared to continued cigarette smoking or cessation were synthesized. Sixteen out of eighty-two biomarkers (7 exposure and 9 potential harm) measured in HTP trials have been associated with tobacco use and lung cancer, dose-dependently correlated with smoking, modifiable upon cessation, measured within an appropriate timeframe, and had results published. Three of the exposure biomarkers significantly improved in smokers who switched to HTPs and were not significantly different from cessation. The remaining 13 biomarkers did not improve-in some instances worsening upon switching to HTPs-or were inconsistently affected across studies. There were no appropriate data to estimate the lung cancer risk of HTPs in non-smokers. The appropriateness of existing biomarker data in assessing lung cancer risk of HTPs, both relative to cigarettes and their absolute risk, is limited. Furthermore, findings on the most appropriate biomarkers were conflicting across studies and largely showed no improvement following a switch to HTPs. Biomarker data are fundamental to assessing the reduced risk potential of HTPs. Our evaluation suggests much of the existing biomarker data on HTPs is inappropriate for determining the risk of lung cancer posed by HTPs. In particular, there is a paucity of data on the absolute lung cancer risk of HTPs, which could be obtained from comparisons to smokers who quit and never smokers exposed to or using HTPs. There is an urgent need for further exploration of the lung cancer risks posed by HTPs, via clinical trials and, in the long-term, confirmation of these risks via epidemiological studies. However, careful consideration should be given to biomarker selection and study design to ensure both are appropriate and will provide valuable data.

Stratification of Lung Cancer Risk with Thoracic Imaging Phenotypes.

In lung cancer screening, estimation of future lung cancer risk is usually guided by demographics and smoking status. The role of constitutional profiles of human body, a.k.a. body habitus, is increasingly understood to be important, but has not been integrated into risk models. Chest low dose computed tomography (LDCT) is the standard imaging study in lung cancer screening, with the capability to discriminate differences in body composition and organ arrangement in the thorax. We hypothesize that the primary phenotypes identified using lung screening chest LDCT can form a representation of body habitus and add predictive power for lung cancer risk stratification. In this pilot study, we evaluated the feasibility of body habitus image-based phenotyping on a large lung screening LDCT dataset. A thoracic imaging manifold was estimated based on an intensity-based pairwise (dis)similarity metric for pairs of spatial normalized chest LDCT images. We applied the hierarchical clustering method on this manifold to identify the primary phenotypes. Body habitus features of each identified phenotype were evaluated and associated with future lung cancer risk using time-to-event analysis. We evaluated the method on the baseline LDCT scans of 1,200 male subjects sampled from National Lung Screening Trial. Five primary phenotypes were identified, which were associated with highly distinguishable clinical and body habitus features. Time-to-event analysis against future lung cancer incidences showed two of the five identified phenotypes were associated with elevated future lung cancer risks (HR=1.61, 95% CI = [1.08, 2.38], p=0.019; HR=1.67, 95% CI = [0.98, 2.86], p=0.057). These results indicated that it is feasible to capture the body habitus by image-base phenotyping using lung screening LDCT and the learned body habitus representation can potentially add value for future lung cancer risk stratification.

Lung cancer incidence attributable to residential radon exposure in Finland

This study aimed to estimate (1) the number of avoidable lung cancer cases attributable to residential radon in Finland in 2017, separately by age, sex, dwelling type and smoking status, (2) the impact of residential radon alone and the joint effect of residential radon and smoking on the number of lung cancers and (3) the potential decrease in the number of radon-attributable lung cancers if radon concentrations exceeding specified action levels (100, 200 and 300 Bq m−3) would have been mitigated to those levels. Population-based surveys of radon concentrations and smoking patterns were used. Observed radon levels were contrasted with 25 Bq m−3 representing a realistic minimum level of exposure. Lung cancer risk estimates for radon and smoking were derived from literature. Lastly, the uncertainty due to the estimation of exposure and risk was quantified using a computationally derived uncertainty interval. At least 3% and at most 8% of all lung cancers were estimated as being attributable to residential radon. For small cell carcinoma, the proportion of cases attributable to radon was 8–13%. Among smokers, the majority of the radon-related cases were attributable to the joint effect of radon and smoking. Reduction of radon exposure to 100 Bq m−3 action level would eliminate approximately 30% of radon-attributable cases. Estimates were low compared with the literature, given the (relatively high) radon levels in Finland. This was mainly due to the lower radon levels and higher smoking prevalence in flats than in houses and a more realistic point of comparison, factors which have been ignored in previous studies. The results can guide actions in radon protection and in prevention of lung cancers.

A preliminary study on real-time Rn/Tn discriminative detection using air-flow delay in two ion chambers in series

Due to its short half-life, thoron gas has been assumed to have negligible health hazards on humans compared to radon. But, one of the decay products with a long half-life can make it to be transported to a long distance and to cause a severe internal dose through respiration. Since most commercial radon detectors can not discriminate thoron signals from radon signals, it is very common to overestimate radon doses which in turn result in biased estimation of lung cancer risk in epidemiological studies. Though some methods had been suggested to measure thoron and radon separately, they could not be used for real-time measurement because of CR-39 or LR-115. In this study, an effective method was suggested to measure radon and thoron separately from the free air. It was observed that the activity of thoron decreases exponentially due to delay time caused by a long pipe between two chambers. Therefore from two ion chambers apart in time, it was demonstrated that thoron and radon could be measured separately and simultaneously. We also developed a collimated alpha source and with this source and an SBD, we could convert the ion chamber reading to count rate in cps.

Mortality among Tennessee Eastman Corporation (TEC) uranium processing workers, 1943–2019

Background There are few occupational studies of women exposed to ionizing radiation. During World War II, the Tennessee Eastman Corporation (TEC) operated an electromagnetic field separation facility of 1152 calutrons to obtain enriched uranium (235U) used for the Hiroshima atomic bomb. Thousands of women were involved in these operations. Materials and methods A new study was conducted of 13,951 women and 12,699 men employed at TEC between 1943 and 1947 for at least 90 days. Comprehensive dose reconstruction techniques were used to estimate lung doses from the inhalation of uranium dust based on airborne measurements. Vital status through 2018/2019 was obtained from the National Death Index, Social Security Death Index, Tennessee death records and online public record databases. Analyses included standardized mortality ratios (SMRs) and Cox proportional hazards models. Results Most workers were hourly (77.7%), white (95.6%), born before 1920 (58.3%), worked in dusty environments (57.0%), and had died (94.9%). Vital status was confirmed for 97.4% of the workers. Women were younger than men when first employed: mean ages 25.0 years and 33.0 years, respectively. The estimated mean absorbed dose to the lung was 32.7 mGy (max 1048 mGy) for women and 18.9 mGy (max 501 mGy) for men. The mean dose to thoracic lymph nodes (TLNs) was 127 mGy. Statistically significant SMRs were observed for lung cancer (SMR 1.25; 95% CI 1.19, 1.31; n = 1654), nonmalignant respiratory diseases (NMRDs) (1.23; 95% CI 1.19, 1.28; n = 2585), and cerebrovascular disease (CeVD) (1.13; 95% CI 1.08, 1.18; n = 1945). For lung cancer, the excess relative rate (ERR) at 100 mGy (95% CI) was 0.01 (–0.10, 0.12; n = 652) among women, and −0.15 (–0.38, 0.07; n = 1002) among men based on a preferred model for men with lung doses <300 mGy. NMRD and non-Hodgkin lymphoma were not associated with estimated absorbed dose to the lung or TLN. Conclusions There was little evidence that radiation increased the risk of lung cancer, suggesting that inhalation of uranium dust and the associated high-LET alpha particle exposure to lung tissue experienced over a few years is less effective in causing lung cancer than other types of exposures. There was no statistically significant difference in the lung cancer risk estimates between men and women. The elevation of certain causes of death such as CeVD is unexplained and will require additional scrutiny of workplace or lifestyle factors given that radiation is an unlikely contributor since only the lung and lymph nodes received appreciable dose.

Swiss pilot low-dose computed tomography lung cancer screening study

Abstract Objective Low-dose computed tomography (LDCT) lung cancer screening is endorsed by US guidelines and has recently been shown effective in a large European randomized controlled trial. Nevertheless, actual realization of a lung cancer screening program is challenging and depends on country-specific factors. This pilot study aimed to evaluate implementation, execution, and performance of LDCT lung cancer screening in Switzerland. Methods Since October 2018, asymptomatic participants aged 55–74 years with more than 30 pack-years smoking history were enrolled at a tertiary hospital in Switzerland. Participants with history of lung cancer, major (palliative) health problems or those that had a thorax CT scan 18 months prior to enrollment were excluded. First, we evaluated lung cancer risk according to NLST guidelines. Second, we estimated lung cancer risk using the PLCOm2012 model risk calculator with threshold of 5%. Lung nodules were assessed according to Lung-RADS (Version 1.1. 2019). Participants were recruited through flyers, a newspaper article and pulmonary specialists. Screening consisted of one LDCT-scan, follow-up was recommended for suspicious nodules only. LDCT assessment was performed by two radiologists, one of them a board certified chest radiologist. Enrollment and follow-up are currently ongoing. Results To date, 75 participants (25 (33%) females) with a median age of 62 years (interquartile range [IQR] 56–67 years) were included. Median number of pack years smoked was 49 (IQR 41–58 pack years). Median PLCOm2012 6-year lung cancer probability was 2.7% (IQR 2.6–2.9%), 19 (26%) participants had stopped smoking before enrollment. 6 participants required follow up imaging of suspect nodules, resulting in a recall rate of 8%. At baseline, lung cancer was found in 2 (2.7%, one squamous cell (stage IIIA) and one adenocarcinoma (stage IV)) participants. Conclusion In this Swiss LDCT lung cancer screening pilot study using modified inclusion criteria, 2.7% were diagnosed with lung cancer to date.

Метод оценки радиационных рисков заболеваемости солидными злокачественными новообразованиями, учитывающий возможные ошибки в постановке и регистрации диагнозов

A bias in radiation risk estimates may be caused by diagnostic errors. In this paper radiation risk estimates are examined with the use of the contingency table 2х2 of irradiated cancer cases with account of sensitivity and specificity indicators of diagnostic methods accuracy were examined. Radiation risk is estimated by metrics of the odds ratio (OR) and relative risk ratio (RR). It is shown that the estimation of radiation risk in the RR metric did not depend on the diagnostic sensitivity indicator, and therefore is preferable, compared to the OR metric. When the specificity of the diagno-sis is reduced, the RR value increases, compared to the risk estimated with the use of observed number of cancer cases regardless of the specificity. As a numerical example, data on trachea, bronchus and lung cancers in a cohort of the Chernobyl cleanup workers of Russia formed by using data monitored within frames of the National Radiation Epidemiological Register (NRER) from 1992 to 2020. During this period, 2,222 cancer cases were reported in the cohort of 67,587 people. The cohort members were divided into two groups, those who were unexposed to radiation (radia-tion doses less than 0.1 Gy) and other, exposed to radiation. If the specificity indicator is taken to be 100%, then the RR=1.07 at 95% CI (1.02; 1.13). The estimates of radiation risks of malignant neoplasms obtained directly from the observed number of cancer cases in exposed and unexposed groups of people, excluding the specificity and sensitivity indicators of diagnosis accuracy, are the lower estimates of radiation risk. As the probability of diagnostic errors increases (as the specificity and sensitivity of diagnostic tests decrease), and when these errors are taken into account, the es-timates of radiation risks increase. If the specificity is reduced to 98.7% CI radiation risk estimates for trachea, bronchus and lung cancer among cleanup workers of the Chernobyl accident increase to RR=1.13, but it is within 95% CI of the RR estimate if specificity is 100%. The radiation risk as-sessment approach used in the study, based on the comparison of exposed and unexposed groups of cleanup workers in OR or RR metrics, imposes high requirements to the specificity indicator of the complex of diagnostic methods in trachea, bronchus and lung (Sp&gt;98.7%) in order to obtain unbiased estimates of radiation risks of cancer in the cleanup workers received dose below 1 Sv. These requirements are not supported by current screening methods, they can be fulfilled as a result of longterm medical monitoring within the system of the NRER.

Cancer Risk Estimation Combining Lung Screening CT with Clinical Data Elements.

To develop a model to estimate lung cancer risk using lung cancer screening CT and clinical data elements (CDEs) without manual reading efforts. Two screening cohorts were retrospectively studied: the National Lung Screening Trial (NLST; participants enrolled between August 2002 and April 2004) and the Vanderbilt Lung Screening Program (VLSP; participants enrolled between 2015 and 2018). Fivefold cross-validation using the NLST dataset was used for initial development and assessment of the co-learning model using whole CT scans and CDEs. The VLSP dataset was used for external testing of the developed model. Area under the receiver operating characteristic curve (AUC) and area under the precision-recall curve were used to measure the performance of the model. The developed model was compared with published risk-prediction models that used only CDEs or imaging data alone. The Brock model was also included for comparison by imputing missing values for patients without a dominant pulmonary nodule. A total of 23 505 patients from the NLST (mean age, 62 years ± 5 [standard deviation]; 13 838 men, 9667 women) and 147 patients from the VLSP (mean age, 65 years ± 5; 82 men, 65 women) were included. Using cross-validation on the NLST dataset, the AUC of the proposed co-learning model (AUC, 0.88) was higher than the published models predicted with CDEs only (AUC, 0.69; P < .05) and with images only (AUC, 0.86; P < .05). Additionally, using the external VLSP test dataset, the co-learning model had a higher performance than each of the published individual models (AUC, 0.91 [co-learning] vs 0.59 [CDE-only] and 0.88 [image-only]; P < .05 for both comparisons). The proposed co-learning predictive model combining chest CT images and CDEs had a higher performance for lung cancer risk prediction than models that contained only CDE or only image data; the proposed model also had a higher performance than the Brock model.Keywords: Computer-aided Diagnosis (CAD), CT, Lung, Thorax Supplemental material is available for this article. © RSNA, 2021.

P61.10 Swiss Pilot Low-Dose Computed Tomography Lung Cancer Screening Study

Low-dose computed tomography (LDCT) lung cancer screening is endorsed by United States guidelines and has recently been shown effective in a large European randomized controlled trial. Nevertheless, the actual realization of a lung cancer screening program is challenging and depends on country-specific factors. This pilot study aimed to evaluate implementation, execution and performance of LDCT lung cancer screening in Switzerland. Starting from October 2018, asymptomatic participants aged 55-74 years with more than 30 pack-years smoking history were enrolled at a tertiary hospital in Switzerland. Participants with history of lung cancer, major (palliative) health problems or those that had a thorax CT scan 18 months prior to enrollment were excluded. First line we evaluated lung cancer risk according NLST guidelines. Secondly, we estimated lung cancer risk using the PLCOm2012 model risk calculater with a threshold of 5%. Lung nodules were assessed according Lung-RADS 1.1 {ACoR. Lung-Screening Reporting and Data System (LungRADS) Version 1.1. 2019}. Participants were predominantly recruited through flyers, a newspaper article and pulmonary specialists. Screening consisted of one LDCT-scan and follow-up was recommended for suspicious nodules only. LDCT assessment was performed by two radiologists, one of them a board certified chest radiologist. Enrollment and follow-up are currently ongoing. To date, 75 participants with a median age of 62 years (interquartile range [IQR] 56-67 years) were included. The median number of pack years smoked was 49 (IQR 41-58 pack years) and 25 (33%) were female. The median PLCOm2012 6-year lung cancer probability was 2.7% (IQR 2.6-2.9%) and 19 (26%) participants had stopped smoking before enrollment. Of the 75 participants, 61 (81%) were found to have calcified or non-calcified lung nodules. 6 participants required follow up imaging of suspect nodules which resulted in a recall rate of 8%. At baseline, lung cancer was found in 2 (2.7%) participants. The lung cancers were one squamous cell carcinoma (stage IIIA) and one adenocarcinoma (stage IV). In this Swiss LDCT lung cancer screening pilot study using modified inclusion criteria, lung nodules were found in a significant number of participants of whom 2.7 % were diagnosed with lung cancer to date. To date, the recall rate for follow-up imaging is 8%.

The possible impact of passive smoke exposure on radiation-related risk estimates for lung cancer among women: the life span study of atomic bomb survivors

Purpose Analyses of the Life Span Study cohort of atomic bomb survivors have shown a statistically significant sex difference in the excess risk of incident lung cancer due to radiation exposure, with the radiation-related excess relative risk per gray (ERR/Gy) for women approximately 4 times that for men, after accounting for active smoking. We sought to determine the extent to which this risk difference could be explained by adjustment for passive smoke exposure, which is a known risk factor for lung cancer that was not measured among Life Span Study participants, and which could be particularly influential among female never-smokers. Materials and methods The Life Span Study includes survivors of the atomic bombings of Hiroshima and Nagasaki and city residents who were not in either city at the time of the bombings, matched to survivors on city, sex, and age. First primary lung cancers were identified from population-based cancer registries between 1958 and 2009. Data on active smoking were obtained from mailed surveys and in-person questionnaires (1965–1991). We calculated passive smoke exposure for female never-smokers by attributing smoking pack-years at various intensities (5–50%) based on smoking patterns among men, stratified by city, birth year, radiation dose, and lung cancer status. Poisson regression models with additive and multiplicative interactions between radiation dose and smoking were used to estimate sex-specific radiation-related excess relative risks for lung cancer. Results During the study period, 2,446 first primary lung cancers were identified among 105,444 study participants. On average, male smokers started smoking 19.5 cigarettes per day at 21.5 years old. Partially attributing male smoking patterns to female never-smokers—to approximate passive smoke exposure—yielded lower radiation-related ERR/Gy estimates for women under a multiplicative radiation-smoking interaction model, leading to a lower female-to-male ratio of ERR/Gy estimates; however, this difference was evident only at very high passive smoke intensities. Under an additive radiation-smoking interaction model, the results were unchanged. Conclusions Our results are consistent with the possibility that failure to account for passive smoke might contribute, in small part, to the higher radiation risk estimates for lung cancer among women compared to men in the Life Span Study.

Joint Spatio-Temporal Modeling of Low Incidence Cancers Sharing Common Risk Factors

In this article, we present a joint modeling approach that com bines information from multiple diseases. Our model can be used to obtain more reliable estimates in rare diseases by incorporating information from more common diseases for which there exists a shared set of important risk factors. Information is shared through both a latent spatial process and a latent temporal process. We develop a fully Bayesian hierarchical imple mentation of our spatio-temporal model in order to estimate relative risk, adjusted for age and gender, at the county level in Iowa in five-year intervals for the period 1973–2002. Our analysis includes lung, oral, and esophageal cancers which are related to excessive tobacco and alcohol use risk factors. Lung cancer risk estimates tend to be stable due to the large number of occurrences in small regions, i.e. counties. The lower risk cancers (oral and esophageal) have fewer occurrences in small regions and thus have estimates that are highly variable and unreliable. Estimates from individual and joint modeling of these diseases are examined and compared. The joint modeling approach has a profound impact on estimates regarding the low risk oral and esophageal cancers while the higher risk lung cancer is minutely impacted. Clearer spatial and temporal patterns are obtained and the standard errors of the estimates are reduced leading to more reliable estimates.

Cave radon exposure, dose, dynamics and mitigation

Many caves around the world have very high concentrations of naturally occurring 222Rn that may vary dramatically with seasonal and diurnal patterns. For most caves with a variable seasonal or diurnal pattern, 222Rn concentration is driven by bi-directional convective ventilation, which responds to external temperature contrast with cave temperature. Cavers and cave workers exposed to high 222Rn have an increased risk of contracting lung cancer. The International Commission on Radiological Protection (ICRP) has re-evaluated its estimates of lung cancer risk from inhalation of radon progeny (ICRP 115) and for cave workers the risk may now (ICRP 137) be 4–6 times higher than previously recognized. Cave Guides working underground in caves with annual average 222Rn activity &gt; 1,000 Bq/m3 and default ICRP assumptions (2,000 workplace hours per year, equilibrium factor F = 0.4, dose conversion factor DCF = 14 µSv/(kBq h m-3) could now receive a dose of &gt; 20 mSv/y. Using multiple gas tracers (d13 C--CO2, Rn and N2O), linked weather, source gas flux chambers, and convective air flow measurements a previous study unequivocally identified the external soil above Chifley Cave as the source of cave 222Rn. If the source of 222Rn is external to the cave, a strategy to lower cave 222Rn by passively decreasing summer pattern convective ventilation, which draws 222Rn into caves, is possible without harming the cave environment. A small net annual average temperature difference (warmer cave air) due to geothermal heat flux produces a large net annual volumetric air flow bias (2–5:1) favoring a winter ventilation pattern that flushes Rn from caves with ambient air. Rapid anthropogenic climate change over decades may heat the average annual external temperature relative to the cave temperature that is stabilized by the thermal inertia of the large rock mass. Relative external temperature increases due to climate change (Jenolan Caves, 2008–2018, 0.17°C) reduces the winter pattern air flow bias and increases Rn concentration in caves.