The preventative effects of statin on lung cancer development in patients with idiopathic pulmonary fibrosis using the National Health Insurance Service Database in Korea.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA.

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10-4 or 5.57 × 10-4 in the full PUMA cohort and 7.50 × 10-4 or 7.66 × 10-4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10-4 to 9.2 × 10-4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

Association of area-level mortgage denial and guideline-concordant non-small-cell lung cancer care and outcomes in the United States.

BACKGROUND: Racial and socioeconomic disparities in receipt of care for non-small-cell lung cancer (NSCLC) are well described. However, no previous studies have evaluated the association between mortgage denial rates and receipt of timely and guideline-concordant care for NSCLC and patient outcomes. METHODS: We identified individuals ≥18 years diagnosed with NSCLC between 2014 and 2019 from the National Cancer Database. Using the Home Mortgage Disclosure Act database, we calculated the proportion of denied home loans to total loans at the zip-code level and categorized them into quintiles. Our outcomes included receipt of guideline-concordant care based on clinical and pathologic stage at diagnosis and the National Comprehensive Cancer Network guidelines, time from surgery to chemotherapy initiation, and overall survival. RESULTS: Of the 629,288 individuals diagnosed with NSCLC (median age 69; IQR 61-76 years, 49.1% female), 47.8% did not receive guideline-concordant care. Residing in areas with higher mortgage denial rates and lower income was associated with worse guideline-concordant care overall (aRR = 1.28; 95% CI = 1.25-1.32) and for each cancer treatment modality, worse receipt of timely chemotherapy (aHR = 1.14; 95% CI = 1.11-1.17) and worse overall survival (aHR = 1.21; 95% CI = 1.19-1.22), compared with residing in areas with the lowest mortgage denial rate and highest income. CONCLUSIONS: Area-level mortgage denial rate was associated with worse receipt of timely and guideline-concordant NSCLC care and survival. This highlights the critical need to understand and address systemic practices, such as mortgage denial, that limit access to resources and are associated with worse access to quality cancer care and outcomes.

Lung Cancer in Women: The Past, Present, and Future.

Lung cancer is the leading cause of cancer death for women in multiple countries including the United States. Women are exposed to unique risk factors that remain largely understudied such as indoor pollution, second-hand tobacco exposure, biological differences, gender differences in tolerability and response to therapy in lung cancer, and societal gender roles, that create distinct survivorship needs. Women continue to lack representation in lung cancer clinical trials and are typically treated with data generated from majority male patient study populations, which may be inappropriate to extrapolate and generalize to females. Current lung cancer treatment and screening guidelines do not incorporate sex-specific differences and physicians also often do not account for gender differences when choosing treatments or discussing survivorship needs. To best provide targeted treatment approaches, greater representation of women in lung cancer clinical trials and further research is necessary. Clinicians should understand the unique factors and consequences associated with lung cancer in women; thus, a holistic approach that acknowledges environmental and societal factors is necessary.

Cancer in Victorian prisoners: a description of cancer diagnoses, demographics, risk factors and barriers to optimal care.

BACKGROUND: The Victorian prison population is growing and ageing. Little has been documented about this group's cancer incidence, presentation or treatment. AIMS: To conduct a retrospective review of Victorian prisoners with cancer, including assessment of change over 15 years and adequacy of treatment delivery. METHODS: Detailed demographic, cancer and treatment data were collected for all prisoners with malignancy treated at St Vincent's Hospital Melbourne from 2002 to 2017. Detailed analysis of adherence to Optimal Care Guidelines was undertaken for a subset. Descriptive statistics were used. RESULTS: We identified 200 cancers in 191 prisoners. The population was predominantly male (185 of 191, 93%), with a median age of 54 years. Rates of cigarette smoking (118 of 191, 59%), mental illness (92 of 191, 46%) and intravenous drug use (59 of 191, 29.5%) were high. Exposure-related cancers predominated (nonmelanoma skin cancer, lung cancer and hepatoma). Most were symptomatic (154 of 191, 77%) and almost one-third had incurable disease at diagnosis (64 of 191, 32%). The number of prisoners with cancer increased over time (2002-2006 [T1], n = 31 vs 2012-2016 [T3], n = 101), as did the median age (45 years in T1 vs 55 years in T3) and rates of mental illness (10 of 31 [32%] in T1 vs 55 of 101 [54%] in T3). Delayed treatment initiation occurred in eight of 12 (66%) assessable patients, largely because of nonattendance. CONCLUSIONS: Victorian prisoners with cancer are at risk of poor outcomes because of late presentation, delayed treatment initiation and medical comorbidities. Tailored interventions are urgently required to improve the provision of timely, comprehensive cancer care to this vulnerable and growing population.

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.

Risk model-based management for second primary lung cancer among lung cancer survivors through a validated risk prediction model.

BACKGROUND: Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk-prediction model (called SPLC-RAT) was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. The predictive performance of SPLC-RAT was evaluated in a hospital-based cohort of lung cancer survivors. METHODS: The authors analyzed data from 8448 ever-smoking patients diagnosed with initial primary lung cancer (IPLC) in 1997-2006 at Mayo Clinic, with each patient followed for SPLC through 2018. The predictive performance of SPLC-RAT and further explored the potential of improving SPLC detection through risk model-based surveillance using SPLC-RAT versus existing clinical surveillance guidelines. RESULTS: Of 8448 IPLC patients, 483 (5.7%) developed SPLC over 26,470 person-years. The application of SPLC-RAT showed high discrimination area under the receiver operating characteristics curve: 0.81). When the cohort was stratified by a 10-year risk threshold of ≥5.6% (i.e., 80th percentile from the SPLC-RAT development cohort), the observed SPLC incidence was significantly elevated in the high-risk versus low-risk subgroup (13.1% vs. 1.1%, p < 1 × 10-6 ). The risk-based surveillance through SPLC-RAT (≥5.6% threshold) outperformed the National Comprehensive Cancer Network guidelines with higher sensitivity (86.4% vs. 79.4%) and specificity (38.9% vs. 30.4%) and required 20% fewer computed tomography follow-ups needed to detect one SPLC (162 vs. 202). CONCLUSION: In a large, hospital-based cohort, the authors validated the predictive performance of SPLC-RAT in identifying high-risk survivors of SPLC and showed its potential to improve SPLC detection through risk-based surveillance. PLAIN LANGUAGE SUMMARY: Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC). However, no evidence-based guidelines for SPLC surveillance are available for lung cancer survivors. Recently, an SPLC risk-prediction model was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. Using a large, real-world cohort of lung cancer survivors, we showed the high predictive accuracy and risk-stratification ability of the SPLC risk-prediction model. Furthermore, we demonstrated the potential to enhance efficiency in detecting SPLC using risk model-based surveillance strategies compared to the existing consensus-based clinical guidelines, including the National Comprehensive Cancer Network.

Paracelsian 'Bergsucht' - lung cancer or radiation-induced fibrosis?

PURPOSE: Assessment of absorbed doses on organs and tissues of miners during radon exposure in the Schneeberg mines in the sixteenth century and calculation of the probability of occurrence of radiation-induced lung cancer and lung fibrosis, considering the life expectancy characteristic and the absence of smoking. MATERIALS AND METHODS: The expected radon concentration at the Schneeberg mines has been estimated using published data. Modeling of the accumulation of radon in the working tunnels of mine workings was carried out using the RESRAD-Build 4.0, based on the radium concentration in soil and geometric parameters of the mining tunnel from the engravings in Agricola's book. The dynamics of radionuclides in the human body were performed using the WinAct software in accordance with data from ICRP Publications 130 and 137. The values of absorbed doses on the tissues of the respiratory tract were obtained using the IDAC 2.1 program. Several models based on the epidemiology of uranium miners have been used to calculate radiation risks from radon exposure. The probability of male survival at birth and the age-specific frequency of spontaneous lung cancer not associated with radiation for miners of the sixteenth century (nonsmoking men aged 20-40 years) were estimated to properly calculate the radiation risks. RESULTS: The expected radon concentration in the Schneeberg mines was assessed in the range of 75-100 kBq m-3. The average value of the equilibrium factor was estimated as 0.49 ± 0.03. The annual exposure of miners to radon decay products was assessed as 125-165 WLM year-1. The annual values of absorbed doses to different sections of the respiratory tract were calculated, the maximum absorbed doses of α-radiation are formed on the bronchial and bronchiolar regions of the lungs (2.23 Gy year-1). The deterministic effects as radiation fibrosis of the lungs with 10 years of experience in the mines of Schneeberg have a probability of occurrence from 60 to 100%. All the models used for radiation risk assessments showed that the lifetime risk of developing lung cancer for nonsmoking Schneeberg miners is many times lower than the risk of developing deterministic radiation effects. In contrast, for the smoking cohort of miners in the nineteenth century lung cancer become the dominant cause of death. CONCLUSIONS: The deterministic radiation effects of Schneeberg miners in sixteenth century, exposed to extremely high levels of radon, such as radiation pneumosclerosis or pulmonary fibrosis, are more likely than the development of radiation-induced lung cancer.

[Tobacco - from medical panacea to deadly drug]. / Tabak ­ vom medizinischen Allheilmittel zur tödlichen Droge.

Medical views on the value and risks of tobacco use have changed radically over the centuries. In the 16th century, tobacco was introduced to continental Europe as a medicinal plant and quickly rose to become a "cure-all." When hedonistic pipe smoking became widespread in continental Europe during the Thirty Years' War, physicians warned of the consequences of tobacco abuse. For centuries, tobacco herb was now considered both harmful and curative.The sharp increase in tobacco consumption in the first decades of the twentieth century correlated with an increase in lung cancer, which until then had been little observed. Statistical proof of the direct correlation was provided in the twenties and thirties by Fritz Lickint, among others. In 1939, the Cologne physician Franz Hermann Müller presented the first case-control study on the relationship between smoking and lung carcinoma, which received little international attention. The epidemiological studies published in the 1950s by English and American scientists were based on the same scientific approach as Müller's work but were now considered groundbreaking.

Indoor radon exposure and living conditions in patients with advanced lung cancer in Lublin region, Poland.

OBJECTIVE: Radon (Rn-222) is a noble gas formed in the uranium path (U-238) as a decay product of radium (Ra-226). It is estimated to cause between 3% to 14% of all lung cancers, depending on the national average radon level and smoking prevalence. Radon molecules emit alpha radiation, which is characterized by low permeability through tissues, but due to its remarkably high energy, it has a high potential for DNA damage. The aim of our research was to assess the radon concentration inside the houses of patients with advanced lung cancer and to analyze their socio-economics status. PATIENTS AND METHODS: The measurements of radon concentration were performed in 102 patients with stage 3B or higher lung cancer in the region of Lublin, Poland. One month of radon exposure measurement was performed with alpha-track detectors. In addition, patients filled in a detailed survey about factors that might influence the concentration of radon inside their houses. RESULTS: The average concentration of radon during the exposure of the detector in the residential premises of the respondents was at the level of 69.0 Bq/m3 [37.0-117.0]. A few significant correlations were discovered, e.g., higher levels of radon in countryside houses or in houses equipped with air conditioning. CONCLUSIONS: As radon exposure is a modifiable risk factor for lung cancer, it is extremely important to find factors that may reduce its concentration in dwelling places. Since our research was performed in houses of people with lung cancer, taking corrective actions based on our findings could prevent new lung cancer incidence in patients' flatmates.

Opium, phencyclidine, and crack cocaine smoking associations with lung and upper aerodigestive tract cancers: exploratory findings from a case-control study in Los Angeles County.

Background: Illicit drug use has become a global epidemic, yet it is unclear if drug smoking increases the risk of tobacco-related cancers.Objectives: We aimed to evaluate hypothesized associations between smoking three drugs - opium, phencyclidine (PCP) and crack cocaine and lung and upper aerodigestive tract (UADT) cancers.Methods: A population-based case-control study with 611 lung cancer cases (50% male), 601 UADT cancers cases (76% male), and 1,040 controls (60% male) was conducted in Los Angeles County (1999-2004). Epidemiologic data including drug smoking histories were collected in face-to-face interviews. Associations were estimated with logistic regressions.Results: Adjusting for potential confounders, ever vs. never crack smoking was positively associated with UADT cancers (aOR = 1.56, 95% CI: 1.05, 2.33), and a dose-response relationship was observed for lifetime smoking frequency (p for trend = .024). Heavy (> median) vs. never crack smoking was associated with UADT cancers (aOR = 1.81, 95% CI: 1.07, 3.08) and lung cancer (aOR = 1.58, 95% CI: 0.88, 2.83). A positive association was also observed between heavy PCP smoking and UADT cancers (aOR = 2.29, 95% CI: 0.91, 5.79). Little or no associations were found between opium smoking and lung cancer or UADT cancers.Conclusion: The positive associations between illicit drug use and lung and/or UADT cancers suggest that smoking these drugs may increase the risk of tobacco-related cancers. Despite the low frequency of drug smoking and possible residual confounding, our findings may provide additional insights on the development of lung and UADT cancers.

Opportunities and Challenges of Kava in Lung Cancer Prevention.

Lung cancer is the leading cause of cancer-related deaths due to its high incidence, late diagnosis, and limited success in clinical treatment. Prevention therefore is critical to help improve lung cancer management. Although tobacco control and tobacco cessation are effective strategies for lung cancer prevention, the numbers of current and former smokers in the USA and globally are not expected to decrease significantly in the near future. Chemoprevention and interception are needed to help high-risk individuals reduce their lung cancer risk or delay lung cancer development. This article will review the epidemiological data, pre-clinical animal data, and limited clinical data that support the potential of kava in reducing human lung cancer risk via its holistic polypharmacological effects. To facilitate its future clinical translation, advanced knowledge is needed with respect to its mechanisms of action and the development of mechanism-based non-invasive biomarkers in addition to safety and efficacy in more clinically relevant animal models.

Dietary polyunsaturated fatty acids intake, air pollution, and the risk of lung cancer: A prospective study in UK biobank.

BACKGROUND: Epidemiological evidence on the association between specific types of polyunsaturated fatty acids (PUFAs) intake and lung cancer risk is limited. However, whether dietary-specific PUFAs intake can modify the association between air pollutants and incident lung cancer remains unknown. METHODS: Cox proportional hazard models and restricted cubic spline regression were used to evaluate the associations of omega-3 PUFAs, omega-6 PUFAs and the ratio of omega-6 PUFAs to omega-3 PUFAs intake with lung cancer risk. Furthermore, we evaluated the associations between air pollutants and incident lung cancer, and whether dietary-specific PUFAs intake would modify the relationship using stratification analyses. RESULTS: This study found significant associations between the risk of lung cancer and omega-3 PUFAs intake (hazard ratio [HR], 0.82; 95 % confidence interval [CI], 0.73-0.93; per 1 g/d), and omega-6 PUFAs intake (HR, 0.98; 95 % CI, 0.96-0.99; per 1 g/d). We did not observe an association between the omega-6 to omega-3 PUFAs intake ratio and incident lung cancer. With regard to air pollution, omega-3 PUFAs intake attenuated the positive relationship between nitrogen oxides (NOx) pollution and lung cancer risk, and an increased incidence of lung cancer was found only in the low omega-3 PUFAs intake group (p < 0.05). Surprisingly, PUFAs intake (regardless of omega-3 PUFAs, omega-6 PUFAs, or in total) reinforced the pro-carcinogenic effects of PM2.5 on lung cancer, and a positive association between PM2.5 pollutants and incident lung cancer was observed only in the high PUFAs groups (p < 0.05). CONCLUSIONS: Higher dietary omega-3 and omega-6 PUFAs intake was associated with a decreased risk of lung cancer in the study population. As omega-3 PUFAs have different modification effects on NOX and PM2.5 air pollution related lung cancer incidence, precautions should be taken when using omega-3 PUFAs as health-promoting dietary supplements, especially in high PM2.5 burden regions.

Calcium Intake and Lung Cancer Risk: A Pooled Analysis of 12 Prospective Cohort Studies.

BACKGROUND: Previous studies on calcium intake and lung cancer risk reported inconsistent associations, possibly due to the differences in intake amounts and contributing sources of calcium and smoking prevalence. OBJECTIVES: We investigated the associations of lung cancer risk with intake of calcium from foods and/or supplements and major calcium-rich foods in 12 studies. METHODS: Data from 12 prospective cohort studies conducted in the United States, Europe, and Asia were pooled and harmonized. We applied the DRI to categorize calcium intake based on the recommendations and quintile distribution to categorize calcium-rich food intake. We ran multivariable Cox regression by each cohort and pooled risk estimates to compute overall HR (95% CI). RESULTS: Among 1,624,244 adult men and women, 21,513 incident lung cancer cases were ascertained during a mean follow-up of 9.9 y. Overall, the dietary calcium intake was not significantly associated with lung cancer risk; the HRs (95% CI) were 1.08 (0.98-1.18) for higher (>1.5 RDA) and 1.01 (0.95-1.07) for lower intake (<0.5 RDA) comparing with recommended intake (EAR to RDA). Milk and soy food intake were positively or inversely associated with lung cancer risk [HR (95% CI) = 1.07 (1.02-1.12) and 0.92 (0.84-1.00)], respectively. The positive association with milk intake was significant only in European and North American studies (P-interaction for region = 0.04). No significant association was observed for calcium supplements. CONCLUSIONS: In this largest prospective investigation, overall, calcium intake was not associated with risk of lung cancer, but milk intake was associated with a higher risk. Our findings underscore the importance of considering food sources of calcium in studies of calcium intake.

Trends in Smoking-Specific Lung Cancer Incidence Rates Within a US Integrated Health System, 2007-2018.

BACKGROUND: At least 10% of lung cancers arise in adults who have never used tobacco. Data remain inconclusive on whether lung cancer incidence has been increasing among adults who have never used tobacco. RESEARCH QUESTION: How have age-adjusted incidence rates of lung cancer changed temporally, especially among adults who have never used tobacco? STUDY DESIGN AND METHODS: Trends in lung cancer incidence were examined using linked electronic health record and cancer registry data on a dynamic cohort of adults ≥ 30 years of age at risk of incident lung cancer between January 1, 2007, and December 31, 2018, from an integrated health-care system in northern California. Truncated age-adjusted lung cancer incidence rates and average annual percentage change (AAPC) in rates were estimated, overall and separately for adults who have ever and never used tobacco by age, sex, and race or ethnicity. RESULTS: The cohort included 3,751,348 adults (52.5% female, 48.0% non-Hispanic White, 63.1% have never used tobacco), among whom 18,627 (52.7% female, 68.6% non-Hispanic White, 15.4% have never used tobacco) received a diagnosis of lung cancer. The overall lung cancer incidence rate declined from 91.1 to 63.7 per 100,000 person-years between 2007 and 2009 and between 2016 and 2018 (AAPC, -3.9%; 95% CI, -4.2% to -3.6%). Among adults who have ever used tobacco, incidence rates declined overall from 167.0 to 113.4 per 100,000 person-years (AAPC, -4.2%; 95% CI, -4.4% to -3.9%) and, to varying degrees, within all age, sex, and racial or ethnic groups. Among adults who have never used tobacco, incidence rates were relatively constant, with 3-year-period estimates ranging from 19.9 to 22.6 per 100,000 person-years (AAPC, 0.9%; 95% CI, -0.3% to 2.1%). Incidence rates for adults who have never used tobacco seemed stable over time, within age, sex, and racial or ethnic groups, except for those of Asian and Pacific Islander (API) origin (AAPC, 2.0%; 95% CI, 0.1%-3.9%), whose rates were about twice as high compared with their counterparts. INTERPRETATION: These observed trends underscore the need to elucidate further the cause of lung cancer in adults who have never used tobacco, including why incidence is higher and rising in API adults who have never used tobacco.

Mechanisms and shapes of causal exposure-response functions for asbestos in mesotheliomas and lung cancers.

This paper summarizes recent insights into causal biological mechanisms underlying the carcinogenicity of asbestos. It addresses their implications for the shapes of exposure-response curves and considers recent epidemiologic trends in malignant mesotheliomas (MMs) and lung fiber burden studies. Since the commercial amphiboles crocidolite and amosite pose the highest risk of MMs and contain high levels of iron, endogenous and exogenous pathways of iron injury and repair are discussed. Some practical implications of recent developments are that: (1) Asbestos-cancer exposure-response relationships should be expected to have non-zero background rates; (2) Evidence from inflammation biology and other sources suggests that there are exposure concentration thresholds below which exposures do not increase inflammasome-mediated inflammation or resulting inflammation-mediated cancer risks above background risk rates; and (3) The size of the suggested exposure concentration threshold depends on both the detailed time patterns of exposure on a time scale of hours to days and also on the composition of asbestos fibers in terms of their physiochemical properties. These conclusions are supported by complementary strands of evidence including biomathematical modeling, cell biology and biochemistry of asbestos-cell interactions in vitro and in vivo, lung fiber burden analyses and epidemiology showing trends in human exposures and MM rates.

Assessing the Contribution of Scanned Outside Documents to the Completeness of Real-World Data Abstraction.

PURPOSE: Electronic health record (EHR) data are widely used in precision medicine, quality improvement, disease surveillance, and population health management. However, a significant amount of EHR data are stored in unstructured formats including scanned documents external to the treatment facility presenting an informatics challenge for secondary use. Studies are needed to characterize the clinical information uniquely available in scanned outside documents (SODs) to understand to what extent the availability of such information affects the use of these real-world data for cancer research. MATERIALS AND METHODS: Two independent EHR data abstractions capturing 30 variables commonly used in oncology research were conducted for 125 patients treated for advanced non-small-cell lung cancer at a comprehensive cancer center, with and without consideration of SODs. Completeness and concordance were compared between the two abstractions, overall, and by patient groups and variable types. RESULTS: The overall completeness of the data with SODs was 77.6% as compared with 54.3% for the abstraction without SODs. The differences in completeness were driven by data related to biomarker tests, which were more likely to be uniquely available in SODs. Such data were prone to missingness among patients who were diagnosed externally. CONCLUSION: There were no major differences in completeness between the two abstractions by demographics, diagnosis, disease progression, performance status, or oral therapy use. However, biomarker data were more likely to be uniquely contained in the SODs. Our findings may help cancer centers prioritize the types of SOD data being abstracted for research or other secondary purposes.

Neighborhood disadvantage is associated with KRAS-mutated non-small cell lung cancer risk.

PURPOSE: It remains unclear why individuals living in disadvantaged neighborhoods have shorter non-small cell lung cancer (NSCLC) survival. It is possible that living in these deprived areas is linked with increased risk of developing aggressive NSCLC biology. Here, we explored the association of somatic KRAS mutations, which are associated with shorter survival in NSCLC patients, and 11 definitions of neighborhood disadvantage spanning socioeconomic and structural environmental elements. METHODS: We analyzed data from 429 NSCLC patients treated at a Comprehensive Cancer Center from 2015 to 2018. Data were abstracted from medical records and each patient's home address was used to assign publicly available indices of neighborhood disadvantage. Prevalence Ratios (PRs) for the presence of somatic KRAS mutations were estimated using modified Poisson regression models adjusted for age, sex, smoking status, race/ethnicity, educational attainment, cancer stage, and histology. RESULTS: In the NSCLC cohort, 29% had KRAS mutation-positive tumors. We found that five deprivation indices of socioeconomic disadvantage were associated with KRAS mutation. A one decile increase in several of these socioeconomic disadvantage indices was associated with a 1.06 to 1.14 increased risk of KRAS mutation. Measures of built structural environment were not associated with KRAS mutation status. CONCLUSION: Socioeconomic disadvantage at the neighborhood level is associated with higher risk of KRAS mutation while disadvantage related to built environmental structural measures was inversely associated. Our results indicate not only that neighborhood disadvantage may contribute to aggressive NSCLC biology, but the pathways linking biology to disadvantage are likely operating through socioeconomic-related stress.

Clinical Multiteam System Composition and Complexity Among Newly Diagnosed Early-Stage Breast, Colorectal, and Lung Cancer Patients With Multiple Chronic Conditions: A SEER-Medicare Analysis.

PURPOSE: Sixty percent of adults have multiple chronic conditions at cancer diagnosis. These patients may require a multidisciplinary clinical team-of-teams, or a multiteam system (MTS), of high-complexity involving multiple specialists and primary care, who, ideally, coordinate clinical responsibilities, share information, and align clinical decisions to ensure comprehensive care needs are managed. However, insights examining MTS composition and complexity among individuals with cancer and comorbidities at diagnosis using US population-level data are limited. METHODS: Using SEER-Medicare data (2006-2016), we identified newly diagnosed patients with breast, colorectal, or lung cancer who had a codiagnosis of cardiopulmonary disease and/or diabetes (n = 75,201). Zaccaro's theory-based classification of MTSs was used to categorize clinical MTS complexity in the 4 months following cancer diagnosis: high-complexity (≥ 4 clinicians from ≥ 2 specialties) and low-complexity (1-3 clinicians from 1-2 specialties). We describe the proportions of patients with different MTS compositions and quantify the incidence of high-complexity MTS care by patient groups. RESULTS: The most common MTS composition was oncology with primary care (37%). Half (50.3%) received high-complexity MTS care. The incidence of high-complexity MTS care for non-Hispanic Black and Hispanic patients with cancer was 6.7% (95% CI, -8.0 to -5.3) and 4.7% (95% CI, -6.3 to -3.0) lower than non-Hispanic White patients with cancer; 13.1% (95% CI, -14.1 to -12.2) lower for rural residents compared with urban; 10.4% (95% CI, -11.2 to -9.5) lower for dual Medicaid-Medicare beneficiaries compared with Medicare-only; and 16.6% (95% CI, -17.5 to -15.8) lower for colorectal compared with breast cancer. CONCLUSION: Incidence differences of high-complexity MTS care were observed among cancer patients with multiple chronic conditions from underserved populations. The results highlight the need to further understand the effects of and mechanisms through which care team composition, complexity, and functioning affect care quality and outcomes.

Opium use and risk of lung cancer: A multicenter case-control study in Iran.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.