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The presentations in this session of the Monticello II conference were aimed at summarizing what is known about asbestiform and non-asbestiform elongate mineral particles (EMPs) and mesothelioma risks based on evidence from experimental and epidemiology studies. Dr. Case discussed case reports of mesothelioma over the last several decades. Dr. Taioli indicated that the epidemiology evidence concerning non-asbestiform EMPs is weak or lacking, and that progress would be limited unless mesothelioma registries are established. One exception discussed is that of taconite miners, who are exposed to grunerite. Drs. Mandel and Odo noted that studies of taconite miners in Minnesota have revealed an excess rate of mesothelioma, but the role of non-asbestiform EMPs in this excess incidence of mesothelioma is unclear. Dr. Becich discussed the National Mesothelioma Virtual Bank (NMVB), a virtual mesothelioma patient registry that includes mesothelioma patients' lifetime work histories, exposure histories, biospecimens, proteogenomic information, and imaging data that can be used in epidemiology research on mesothelioma. Dr. Bernstein indicated that there is a strong consensus that long, highly durable respirable asbestiform EMPs have the potential to cause mesothelioma, but there is continued debate concerning the biodurability required, and the dimensions (both length and diameter), the shape, and the dose associated with mesothelioma risk. Finally, Dr. Nel discussed how experimental studies of High Aspect Ratio Engineered Nanomaterials have clarified dimensional and durability features that impact disease risk, the impact of inflammation and oxidative stress on the epigenetic regulation of tumor suppressor genes, and the generation of immune suppressive effects in the mesothelioma tumor microenvironment. The session ended with a discussion of future research needs.

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.

Open in new tab Download slide OBJECTIVES Non-small-cell lung cancer mortality has declined at a faster rate than incidence due to multiple factors, including changes in smoking behaviour, early detection which shifts diagnosis, and novel therapies. Limited resources require that we quantify the contribution of early detection versus novel therapies in improving lung cancer survival outcomes. METHODS Non-small-cell lung cancer patients from the Surveillance, Epidemiology, and End Results-Medicare data were queried and divided into: (i) stage IV diagnosed in 2015 (n  = 3774) and (ii) stage I–III diagnosed in 2010–2012 (n  = 15 817). Multivariable Cox-proportional hazards models were performed to assess the independent association of immunotherapy or diagnosis at stage I/II versus III with survival. RESULTS Patients treated with immunotherapy had significantly better survival than those who did not (HRadj: 0.49, 95% confidence interval: 0.43–0.56), as did those diagnosed at stage I/II versus stage III (HRadj: 0.36, 95% confidence interval: 0.35–0.37). Patients on immunotherapy had a 10.7-month longer survival than those who were not. Stage I/II patients had an average survival benefit of 34 months, compared to stage III. If 25%% of stage IV patients not on immunotherapy received it, there would be a gain of 22 292 person-years survival per 100 000 diagnoses. A switch of only 25% from stage III to stage I/II would correspond to 70 833 person-years survival per 100 000 diagnoses. CONCLUSIONS In this cohort study, earlier stage at diagnosis contributed to life expectancy by almost 3 years, while gains from immunotherapy would contribute ½ year of survival. Given the relative affordability of early detection, risk reduction through increased screening should be optimized. [ABSTRACT FROM AUTHOR]

Rationale: Lung cancer surgical morbidity has been decreasing, increasing attention to quality-of-life measures. A chronic sequela of lung cancer surgery is the use of postoperative oxygen at home after discharge. Prospective studies are needed to identify risk predictors for home oxygen (HO2) use after curative lung cancer surgery. Objectives: To prospectively assess risk factors for postoperative oxygen use and postsurgical morbidity in patients undergoing curative lung cancer surgery. We hypothesized that obesity, poor preoperative pulmonary function, and smoking status would contribute to the risk of postoperative oxygen use. Methods: This study included patients undergoing surgery for a first primary non-small cell lung cancer at Mount Sinai from 2016 to 2020. Univariate, multivariable logistic regression analyses and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were assessed. Results: Of the 433 patients with diagnosed pathologic stage I non-small cell lung cancer, 63 (14.5%) were discharged with HO2. By using multivariable analyses, we found that the body mass index (BMI) (OR for a BMI of 25-30 kg/m2, 4.0; 95% CI, 1.6-11.2; OR for a BMI ⩾30 kg/m2, 6.1; 95% CI, 2.4-17.5) and the preoperative diffusing capacity of the lung for carbon monoxide (DlCO) (OR for a DlCO of <40%, 24.9; 95% CI, 3.6-234.1; OR for a DlCO of 40-59%,  3.1; 95% CI, 1.3-7.2) were significant independent risk factors associated with the risk of HO2 use after adjusting for other covariates. Although current smoking significantly increased the risk in the univariate analysis, it was no longer significant in the multivariable model. Conclusions: Obesity and the DlCO were significant as risk factors for oxygen use at home after discharge. These findings allow for identification of patients at risk of being discharged with HO2 after lung resection surgery. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to identify the association between Thailand's insurance types and stage at presentation, surgical approach, tumor recurrence and cancer-specific survival in resectable non-small cell lung cancer (NSCLC) patients in northern Thailand. Patients and Methods: Medical records of patients with NSCLC who underwent pulmonary resection at Chiang Mai University Hospital from January 2007 through December 2015 were retrospectively reviewed. Patients were divided into two groups: patients with the Universal Coverage Scheme (UCS) or Social Security Scheme (SSS) and patients with the Civil Servant Medical Benefit Scheme (CSMBS) or private insurance (PI). Patient characteristics were assessed. The primary outcome was cancer-specific survival while the secondary outcome was tumor recurrence. Cox's regression and matching propensity score analysis was used to analyze data. Results: This study included 583 patients: 344 with UCS or SSS and 239 with CSMBS or PI. Patients with UCS or SSS were more likely to be active smokers, have a lower percent predicted FEV1, present with higher-stage tumors and worse differentiated tumors, present with tumor necrosis, and undergo an open surgical approach than those with CSMBS or PI. At multivariable analysis of all patients cohort, there were no significant differences in terms of early stage at presentation (adjusted odds ratio (ORadj) = 0.94, 95% confidence interval (CI) = 0.65– 1.37), undergoing lobectomy (ORadj = 0.59, 95% CI = 0.24– 1.46), and recurrent-free survival (adjusted hazard ratio (HRadj) =1.20, 95% CI = 0.88– 1.65) between groups (UCS/SSS versus CSMBS/PI). However, patients with UCS or SSS had shorter cancer-specific survival (HRadj = 1.61, 95% CI = 1.22– 2.15). The results from the propensity score matched patient cohort were not different from those analyses on the full patient cohort. Conclusion: Thai insurance types have an effect on cancer-specific survival. The Thai government should recognize the importance of these differences, and further multi-center studies with a larger sample size are warranted to confirm this result. [ABSTRACT FROM AUTHOR]

Background: Robotic-assisted surgery (RAS) is a novel surgical approach increasingly used for patients with non-small cell lung cancer (NSCLC). However, data comparing the effectiveness and costs of RAS vs open thoracotomy and video-assisted thoracoscopic surgery (VATS) for NSCLC are limited.Methods: Patients > 65 years old with stage I to IIIA NSCLC treated with RAS, VATS, or open thoracotomy were identified from the Surveillance, Epidemiology, and End Results-Medicare database and matched according to age, sex, stage, and extent of resection. Propensity score methods were used to compare adjusted rates of postoperative complications, adequate lymph node staging, survival, and treatment-related costs.Results: In this matched study cohort of 2,766 patients with resected NSCLC, RAS was associated with lower complication rates (OR, 0.57; 95% CI, 0.42-0.79) compared with open thoracotomy, and similar complication rates (OR, 1.02; 95% CI, 0.76-1.37) compared with VATS. Patients undergoing RAS were as likely to have adequate lymph node sampling as those undergoing open thoracotomy (OR, 1.28; 95% CI, 0.94-1.74) or VATS (OR, 0.88; 95% CI, 0.66-1.18). There was no significant difference in overall survival after RAS vs open thoracotomy (hazard ratio, 0.81; 95% CI, 0.63-1.04) or VATS (hazard ratio, 0.91; 95% CI, 0.70-1.18). Costs were similar for RAS ($54,702) vs open thoracotomy ($57,104; P = .08), and higher compared with VATS ($48,729; P = .02).Conclusions: RAS led to improved operative outcomes compared with open thoracotomy but may not offer an advantage over VATS. The comparative effectiveness of RAS should be further evaluated prior to widespread adoption. [ABSTRACT FROM AUTHOR]

Background: Demographic and contextual factors are associated with quality of life (QoL) in older adults and prediagnosis QoL among older adults has important implications for supportive care in older cancer patients. Objective: To examine whether lower educational attainment is associated with poorer QoL among community dwelling older adults just before their diagnosis of lung cancer in a nationally representative sample. Design: This study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) dataset, which provides cancer registry data linked with survey data for Medicare Advantage enrollees. Subjects: Adults 65 years and older at time of diagnosis with first or only primary lung cancer and with at least one survey before their cancer diagnosis. Measurements: Level of education attained was categorized as less than high school (

Background: Lung cancer screening (LCS) is an important secondary prevention measure to reduce lung cancer mortality. The goal of this study was to assess state-level variations in LCS among the US elderly during the first 3 years since Medicare began its LCS reimbursement policy in 2015.Methods: This ecological study examined the relations between LCS utilization density, defined as the number of low-dose CT (LDCT) or shared decision-making and counseling (SDMC) services per 1,000 Medicare fee-for-service (FFS) beneficiaries derived from the Medicare Provider Utilization and Payment Data: Physician and Other Supplier public use file, and state-level factors from several publicly available data sources. The study included Kruskal-Wallis tests and a cluster analysis.Results: In 2017, the median utilization density per 1,000 Medicare FFS beneficiaries was 3.32 for LDCT and 0.46 for SDMC, which was 24 and 13 times the 2015 level, respectively. From 2015 to 2017, the total number of unique providers billed for LCS increased from 222 to 3,444 for LDCT imaging and from 20 to 523 for SDMC. Higher utilizations for both LDCT and SDMC services tended to concentrate in the northeastern and upper Midwest states than in the southwest states. The cluster of states with high utilization density did not include those states with the most lung cancer mortality and/or smoking prevalence.Conclusions: A steady increase was noted in LCS utilization since Medicare began its reimbursement policy. The utilization and its growth varied across the United States and differed between LDCT imaging and SDMC, indicating large growth potentials for LCS and for states with high lung cancer mortality and smoking prevalence. [ABSTRACT FROM AUTHOR]

Background: Low adoption of lung cancer screening is potentially caused by inadequate access to a comprehensive lung cancer screening registry (LCSR), currently a requirement for reimbursement by the Centers for Medicare and Medicaid Services. However, variations in LCSR facilities have not been extensively studied.Methods: We applied a hierarchical clustering method to a comprehensive database integrating state-level LCSR facility density, defined as the number of facilities per 100,000 at-risk persons, lung cancer outcomes including mortality and stage-specific incidence, and socioeconomic and behavioral factors.Results: We found three distinct clusters of LCSR facilities roughly corresponding to the northern (cluster 1), southeastern (cluster 2), and southwestern (cluster 3) states. The southeastern states had the lowest total number of facilities (67 ± 44 in cluster 2, 74 ± 69 in cluster 1, 80 ± 100 in cluster 3), the slowest increase in facilities (23 ± 20 in cluster 2, 26 ± 28 in cluster 1, 27 ± 32 in cluster 3) between 2016 and 2018, and the highest lung cancer burden and current smokers. They ranked second in terms of facility density (2.9 ± 1.0 in cluster 3, 3.8 ± 1.3 in cluster 2, 6.3 ± 2.8 in cluster 1) and increase in facility density (1.1 ± 0.3 in cluster 3, 1.3 ± 0.7 in cluster 2, 2.5 ± 2.5 in cluster 1).Conclusions: We found substantial state-level variability in LCSR facilities tied to lung cancer burden, socioeconomic characteristics, and behavioral characteristics. Given the known risk factors of lung cancer, correcting a suboptimal distribution of screening programs will likely lead to improved lung cancer outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the importance of lung cancer screening and the need to improve access to it globally. It emphasizes the need to identify high-risk individuals and incorporate relevant risk factors, such as family history and exposure to asbestos, into screening criteria. The authors argue that investing in lung cancer CT screenings can save more lives than other treatments like chemotherapy or targeted therapy. While radiomics shows promise for the future, the immediate priority should be expanding access to screenings and enhancing early detection. [Extracted from the article]

Purpose: Summarise survival of patients with resected lung cancers manifesting as part-solid nodules (PSNs).Methods: PubMed/MEDLINE and EMBASE databases were searched for all studies/clinical trials on CT-detected lung cancer in English before 21 December 2015 to identify surgically resected lung cancers manifesting as PSNs. Outcome measures were lung cancer-specific survival (LCS), overall survival (OS), or disease-free survival (DFS). All PSNs were classified by the percentage of solid component to the entire nodule diameter into category PSNs <80% or category PSNs ≥80%.Results: Twenty studies reported on PSNs <80%: 7 reported DFS and 2 OS of 100%, 6 DFS 96.3-98.7%, and 11 OS 94.7-98.9% (median DFS 100% and OS 97.5%). Twenty-seven studies reported on PSNs ≥80%: 1 DFS and 2 OS of 100%, 19 DFS 48.0%-98.0% (median 82.6%), and 16 reported OS 43.0%-98.0% (median DFS 82.6%, OS 85.5%). Both DFS and OS were always higher for PSNs <80%.Conclusion: A clear definition of the upper limit of solid component of a PSN is needed to avoid misclassification because cell-types and outcomes are different for PSN and solid nodules. The workup should be based on the size of the solid component.Key Points: • Lung cancers manifesting as PSNs are slow growing with high cure rates. • Upper limits of the solid component are important for correct interpretation. • Consensus definition is important for the management of PSNs. • Median disease-free-survival (DFS) increased with decreasing size of the nodule. [ABSTRACT FROM AUTHOR]

Video-assisted thoracic surgery (VATS) lobectomy is an appealing alternative to open lobectomy via thoracotomy for non-small-cell lung cancer. However, there is no clear consensus in regard to the superior approach for long-term outcomes. The data are limited to small series, which precludes further clarification. Meta-analysis of these studies was performed in order to obtain a more objective determination of the oncological feasibility of VATS lobectomy. A systematic review of the PubMed and Embase databases was performed. Twenty observational studies reporting long-term outcomes were included, involving 2106 VATS and 2661 thoracotomy patients. There was an advantage in long-term mortality for patients who underwent VATS vs patients who underwent thoracotomy (meta difference in survival: 5%; 95% CI: 3–6%) with large heterogeneity among studies (Q = 42.6; P-value: 0.001; I2 = 55.7%). There was no evidence of publication bias. Compared with open lobectomy, VATS lobectomy appears to have improved long-term outcomes. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer mortality worldwide. A possible carcinogenic role of human papillomavirus (HPV) has been investigated for >20 years and has major clinical and public health implications. We performed a meta-analysis to assess the prevalence of HPV16 and HPV18 in primary lung cancers (2435 subjects from 37 published studies). The overall HPV prevalence ranged from 0.0 to 78.3% with large heterogeneity across geographic regions and histological tissue types. A higher proportion, 50% (7/14), of the European studies reported low or no HPV prevalence (0–10%) compared with the Asian studies, 22% (4/18). When the analysis was limited to HPV16 and HPV18 prevalence, a higher prevalence in Asia (HPV16 = 11.6% and HPV18 = 8.8%) than in Europe (HPV16 = 3.5% and HPV18 = 3.6%) was observed. Studies using HPV-specific primers resulted in higher prevalence rates than consensus HPV primers (HPV16: Asia = 13% and Europe = 6%; HPV18: Asia = 13% and Europe = 5%). Further studies are needed to elucidate the role of HPV in lung carcinogenesis with careful thought given to study design and laboratory detection methods for a more accurate assessment of HPV status in lung tumors. [ABSTRACT FROM PUBLISHER]

This article reports an update of a pooled analysis on metabolic gene polymorphisms and cancer (the Genetic Susceptibility lo Environmental Carcinogens [GSEC] study). The study started in 1997, and has collected data from over 52,000 subjects (half cases, half controls). The distribution of the cases shows that the most represented cancer is lung cancer (6465 cases), followed by bladder cancer (3289 cases), and breast cancer (3232 cases). The analyses conducted on lung cancer and- metabolic gene polymorphisms are summarized and discussed. Pooled analysis allows one to study rare subgroups of subjects, such as lung cancer at young ages, or in nonsmokers, and is a useful approach for generating new working hypothesis and for fostering collaboration. [ABSTRACT FROM AUTHOR]

Gene-environment interactions have been extensively studied in lung cancer. It is likely that several genetic polymorphisms cooperate in increasing the individual risk. Therefore, the study of gene-gene interactions might be important to identify high-susceptibility subgroups. GSEC is an initiative aimed at collecting available data sets on metabolic polymorphisms and the risks of cancer at several sites and performing pooled analyses of the original data. Authors of published papers have provided original data sets. The present paper refers to gene-gene interactions in lung cancer and considers three polymorphisms in three metabolic genes: CYP1A1 , GSTM1 and GSTT1 . The present analyses compare the gene-gene interactions of the CYP1A1*2A , GSTM1 and GSTT1 polymorphisms from studies on lung cancer conducted in Europe and the USA between 1991 and 2000. Only Caucasians have been included. The data set includes 1466 cases and 1488 controls. The only clear-cut association was found with CYP1A1*2A . This association remained unchanged after stratification by polymorphisms in other genes (with an odds ratio [OR] of approximately 2.5), except when interaction with GSTM1 was considered. When the OR for CYP1A1*2A was stratified according to the GSTM1 genotype, the OR was increased only among the subjects who had the null (homozygous deletion) GSTM1 genotype (OR=2.8, 95% CI=0.9-8.4). The odds ratio for the interactive term ( CYP1A1*2A by GSTM1) in logistic regression was 2.7 (95% CI=0.5-15.3). An association between lung cancer and the homozygous CYP1A1*2A genotype is confirmed. An apparent and biologically plausible interaction is suggested between this genotype and GSTM1 . [ABSTRACT FROM AUTHOR]

To investigate the role of microsomal epoxide hydrolase (mEH) polymorphisms in the aetiology of lung cancer and to assess the interaction between mEH polymorphisms and smoking, we performed a meta-analysis of seven published studies, which included 2078 cases and 3081 controls, and a pooled analysis of eight studies (four published and four unpublished at that time) with a total of 986 cases and 1633 controls. The combined metaanalysis odds ratios (ORs) were 0.98 (95% confidence interval [CI] = 0.72-1.35) for polymorphism at amino acid 113 in exon 3 (His/His versus Tyr/Tyr genotype) and 1.00 (95% CI= 0.71-1.41) for polymorphism at amino acid 139 in exon 4 (Arg/Arg versus His/ His genotype). In the pooled analysis, we observed a significant decrease in lung cancer risk (OR = 0.70, 95% CI = 0.51-0.96) for exon 3 His/His genotype after adjustment for age, sex, smoking and centre. The protective effect of exon 3 polymorphism seems stronger for adenocarcinoma of the lung than for other histological types. The OR for high predicted mEH activity, compared with low activity, was 1.54 (95% CI = 0.77-3.07) in the meta analysis and 1.18 (95% CI = 0.92-1.52) in the pooled analysis. We did not find a consistent modification of the carcinogenic effect of smoking according to mEH polymorphism, although the risk of lung cancer decreased among never smokers with high mEH activity and among heavy smokers with the exon 3 His/His genotype. In conclusion, this study suggests a possible effect of mEH polymorphisms at exon 3 in modulating lung cancer. If present, this effect may vary among different populations, possibly because of interaction with genetic or environmental factors. [ABSTRACT FROM AUTHOR]

Background Lobectomy is the recommended treatment for early-stage lung cancer. Little is known about variations of access to health service areas and hospital types for lobectomy overall and according to specific surgical techniques, such as the video-assisted thoracoscopic surgery (VATS). Methods The New York Statewide Planning and Research Cooperative System (2007-2012) was queried for lung cancer patients who underwent elective lobectomy. Hospitals were defined as nearest high-volume hospital (nHVH, reference), distant HVH (dHVH), close or distant low-volume hospital (cLVH or dLVH) using lobectomy volume and travel burden by the distance to nHVH. Results Utilization of hospitals within patients' health service areas ranged between 44% and 82% for three different geographic units. Approximately 26%, 34%, 31%, and 9% of the 9099 lobectomies were performed in nHVH, dHVH, cLVH, and dLVH, respectively. Patients in nHVH were older and more likely to have private insurance. Patients in dHVH were treated more with VATS and by higher volume surgeons, opposite of what observed in cLVH and dLVH. The use of dHVH was associated with more comorbidities and higher income. The use of dLVH was higher in Hispanics and non-Hispanic blacks than that in non-Hispanic whites. The odds of adverse postoperative events were higher in cLVH and dLVH but lower for patients treated with VATS and by high-volume surgeons. Conclusions Multiple factors likely resulted in differences in patterns of elective lobectomy among lung cancer patients. These variations should be taken into account when accessing and planning specialized health care delivery services. [ABSTRACT FROM AUTHOR]

• Never smokers had significantly lower SUVmax and longer VDT compared to smokers. • No difference in SUVmax and VDT by smoking status after adjusting for histology. • Management and screening intervals should be identical, regardless of smoking history. To determine whether radiographic measures of tumor aggressiveness differ by smoking status. All patients diagnosed with non-small-cell lung cancer(NSCLC) ≤ 30 mm in maximum diameter, without clinical evidence of metastasis who had both pre-treatment PET scans and two CT scans at least 90 days apart in a prospective cohort, the Initiative for Early Lung Cancer Research on Treatment(IELCART) at Mount Sinai between 2016 and 2020 were identified. Comparison of two measures of tumor aggressiveness, positron emission tomography(PET) SUVmax and tumor volume doubling time(VDT) by smoking status was performed. Of 417 patients identified, 158 patients had pre-treatment PET scans and at least two CT scans available. The two measures of tumor aggressiveness, SUVmax and VDT values were significantly different between patients who had never smoked and those who smoked: patients who never smoked had lower median SUVmax[2.5(IQR: 1.1–4.8) vs. 4.2(IQR:2.1–9.2),p = 0.002] and longer median VDT[(372.6 days vs. 225.6 days,p = 0.001)] compared to those who smoked. Using multivariable analyses, when adjusting for age and sex alone, SUVmax(p = 0.004) and VDT(p = 0.0001) remained significantly different by smoking status. The final multivariable analysis, adjusted for all three co-variates(sex, age and tumor histology) showed no significant difference in SUVmax and VDT by smoking status [SUVmax(p = 0.25) and VDT(p = 0.06)]. Smoking history does not influence VDT or PET SUVmax measures of lung cancer aggressiveness. [ABSTRACT FROM AUTHOR]

• We compared self-reported and cotinine-based smoking status in non-trial settings. • We focused on a nationally representative sample of adults eligible for lung cancer screening. • The sensitivity, specificity, and Kappa coefficient were 86.4%, 99.7%, and 83.1%, respectively. • Self-reported smoking status is reliable among adults at high risk for developing lung cancer. Self-reported smoking behavior is widely used in identifying the eligibility for lung cancer screening (LCS). In clinical trials, self-reported smoking status was shown to be a reliable measure, while its effectiveness outside of trial settings remains to be clarified. We aimed to verify self-reported smoking status with serum cotinine levels among LCS-eligible adults from the National Health and Nutrition Examination Survey (NHANES). From the combined 1999-2018 NHANES data, we selected adults (aged ≥18 years) with complete data on serum cotinine and smoking behavior, and determined their LCS eligibility according to the United States Preventive Services Task Force recommendation. Using established race/ethnicity specific cotinine cutpoints as the gold standard, we verified self-reported current smoking status with five measures: sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and reliability Kappa. We also compared these performance measures in subgroups stratified by sex, race/ethnicity, education, family income to poverty ratio, health insurance, and secondhand smoking exposure (SHS) at home. All analyses took into account the complex survey design. Approximately 9.3% (n = 2335, equivalent to 8.82 million weighted population) of all adults who currently smoke or formerly smoked were eligible for LCS. The prevalence of current smoking was 52.6% and 60.8% based on self-report and cotinine, respectively. The Se and Sp were 86.4% (95%CI: 83.9%-88.9%) and 99.7% (95%CI: 99.4%-100%), respectively; PPV and NPV were 99.8% (95%CI: 99.6%-100%) and 82.6% (95%CI: 79.4%-85.7%), respectively; and Kappa was 0.83 (95%CI: 0.80-0.86). The reliability Kappa was higher among females than males (0.87 (95%CI: 0.82-0.93)) vs 0.80 (95%CI: 0.77-0.84), the lowest among non-Hispanic white (0.82 (95%CI: 0.78-0.86)), and higher among those with SHS (0.72 (95%CI: 0.63-0.80) vs (0.68 (95%CI: 0.61-0.76)). Self-reported smoking status is reasonably reliable among adults with high risk for developing lung cancer in the general population. [ABSTRACT FROM AUTHOR]

Purpose Lung cancer screening with low-dose computed tomography has been shown to significantly reduce lung cancer–related mortality in high-risk patients. However, patients diagnosed with lung cancer are typically older and often have multiple age- and smoking-related comorbidities. As a result, cancer screening in older adults remains a complex decision, requiring careful consideration of patients' risk characteristics and life expectancy to ensure that the benefits outweigh the risks of screening. In this review, we evaluate the evidence regarding lung cancer screening, with a focus on older patients. Methods PubMed was searched to identify relevant studies evaluating the clinical outcomes of lung cancer screening. The key words used in our search included non–small cell lung cancer (NSCLC), screening, older, comorbidities, computed tomography, and survival . While we primarily looked for articles specific to older patients, we also focused on subgroup analysis in older patients in larger studies. Finally, we reviewed all relevant guidelines regarding lung cancer screening. Findings Guidelines recommend that lung cancer screening be considered in adults aged 55 to 80 years who are at high risk based on smoking history (ie, 30-pack–year smoking history; having smoked within the past 15 years). Patients who fit these criteria have been shown to have a 20% reduction in lung cancer–related mortality with the use of low-dose computed tomography versus chest radiography. High rates of false-positive results and potential overdiagnoses were also observed. Therefore, screening is generally not recommended in adults with severe comorbidities or short life expectancy, who may experience limited benefit and higher risks with screening. However, several studies have shown a benefit with continued lung cancer screening with appropriate selection of older individuals at the highest risk and with the lowest comorbidities. Implications Older patients experience the highest risk for lung cancer incidence and mortality, and stand to be the most likely to benefit from lung cancer screening. However, careful consideration must be given to higher rates of false-positives and overdiagnosis in this population, as well as tolerability of surgery and competing risks for death from other causes. The appropriate selection of older individuals for lung cancer screening can be greatly optimized by using validated risk-based targeting. [ABSTRACT FROM AUTHOR]

We investigated the effects of hospital centralization on the distribution of the individual surgical patient risk in higher versus lower volume hospitals. Lung (n = 28,471) and bladder (n = 8,160) cancer surgical patients were selected from the New York Statewide Planning and Research Cooperative System database, 1997-2011. Estimated patient risk was consistently lower in the highest compared to the lowest hospital volume-quartiles for lung and bladder cancer mortality, complications, and long length of stay. Although centralization has improved outcomes, lower volume hospitals continue to perform surgery on higher surgical risk patients compared to higher volume hospitals. [ABSTRACT FROM AUTHOR]

This is a comprehensive review and re-analysis of available literature to assess the outcome of lung cancer presenting as nonsolid nodules (NSNs), a more indolent form of cancer. PubMed and EMBASE were searched for articles reporting on CT-detected lung cancers manifesting as NSNs published in English on or before July 17, 2015. Only studies including clinicopathologic data, lung cancer-specific survival, or overall survival were included. Data extraction was performed by three independent reviewers using prespecified criteria. Twenty-four articles from 5 countries met criteria and they included 704 subjects with 712 lung cancers manifesting as NSNs. Each article reported from 2 to 100 lung cancer cases with a median follow up of 18–51 months. All NSNs were Stage I adenocarcinoma without pathologic nodal involvement upon resection, except for one case in which the NSN progressed to become part-solid nodule after 6 years of follow-up. The five-year lung cancer-specific survival rate was 100%. These findings suggest an indolent course for lung cancers manifesting as NSNs. [ABSTRACT FROM AUTHOR]

There is an overwhelming abundance of genetic association studies available in the literature, which can often be collectively difficult to interpret. To address this issue, the Venice interim guidelines were established for determining the credibility of the cumulative evidence. The objective of this report is to evaluate the literature on the association of common glutathione S-transferase (GST) variants (GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphism) and lung cancer, and to assess the credibility of the associations using the newly proposed cumulative evidence guidelines.Information from the literature was enriched with an updated meta-analysis and a pooled analysis using data from the Genetic Susceptibility to Environmental Carcinogens database.There was a significant association between GSTM1 null and lung cancer for the meta-analysis (meta odds ratio=1.17, 95% confidence interval: 1.10-1.25) and pooled analysis (adjusted odds ratio=1.10, 95% confidence interval: 1.04-1.16), although substantial heterogeneity was present. No overall association between lung cancer and GSTT1 null or GSTP1 Ile105Val was found. When the Venice criteria was applied, cumulative evidence for all associations were considered ‘weak’, with the exception of East Asian carriers of the G allele of GSTP1 Ile105Val, which was graded as ‘moderate’ evidence.Despite the large amounts of studies, and several statistically significant summary estimates produced by meta-analyses, the application of the Venice criteria suggests extensive heterogeneity and susceptibility to bias for the studies on association of common genetic polymorphisms, such as with GST variants and lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: Tobacco smoking is a major risk factor for lung cancer causing, among other effects, oxidative stress and lipid peroxidation. Malondialdehyde (MDA)–DNA adducts can be induced by direct DNA oxidation and by lipid peroxidation. We measured the relationship between bronchial MDA–DNA adducts and tobacco smoking, cancer status, and selected polymorphisms in 43 subjects undergoing a bronchoscopic examination for diagnostic purposes. MDA–DNA adducts were higher in current smokers than in never smokers (frequency ratio (FR) = 1.51, 95% confidence interval (CI) 1.01–2.26). MDA–DNA adducts were also increased in lung cancer cases with respect to controls, but only in smokers (FR = 1.70, 95% CI 1.16–2.51). Subjects with GA and AA cyclin D1 (CCND1) genotypes showed higher levels of MDA–DNA adducts than those with the wild-type genotype (FR = 1.51 (1.04–2.20) and 1.45 (1.02–2.07)). Lung cancer cases with levels of MDA–DNA adducts over the median showed a worse, but not statistically significant, survival, after adjusting for age, gender, and packyears (hazard ratio = 2.48, 95% CI 0.65–9.44). Our findings reinforce the role of smoking in lung carcinogenesis through oxidative stress. Subjects who carry at least one variant allele of the CCND1 gene could accumulate DNA damage for altered cell-cycle control and reduced DNA repair proficiency. [Copyright &y& Elsevier]