Change in quality of life of stage IA non-small cell lung cancer after surgery or radiation therapy.

Background: Few studies have examined the differential impact of stereotactic body radiotherapy (SBRT) and surgery for early-stage non-small cell lung cancer (NSCLC) on quality of life (QoL) during the first post-treatment year. Methods: A prospective cohort of stage IA NSCLC patients undergoing surgery or SBRT at Mount Sinai Health System had QoL measured before treatment, and 2, 6, and 12 months post-treatment using: 12-item Short Form Health Survey version 2 (SF-12v2) [physical component summary (PCS) and mental component summary (MCS)], Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS), and the Patient Health Questionnaire-4 (PHQ-4) measuring depression and anxiety. Locally weighted scatterplot smoothing (LOWESS) was fitted to identify the best interval knot for the change in the QoL trends post-treatment, adjusted piecewise linear mixed effects model was developed to estimate differences in baseline, 2- and 12-month scores, and rates of change. Results: In total, 503 (88.6%) patients received surgery and 65 (11.4%) SBRT. LOWESS plots suggested QoL changed at 2 months post-surgery. Worsening in PCS was observed for both surgery and SBRT within 2 months after treatment but was only significant for surgical patients (-2.11, P<0.001). Two months later, improvements were observed for surgical but not SBRT patients (0.63 vs. -0.30, P<0.001). Surgical patients had significantly better PCS (P<0.001) and FACT-LCS (P<0.001) scores 1-year post-treatment compared to baseline, but not SBRT patients. Both surgical and SBRT patients reported significantly less anxiety 1-year post-treatment compared to baseline (P<0.001 and P=0.03). Decrease in depression from baseline to 1-year post-treatment was only significant for surgical patients (P<0.001). Conclusions: Post-treatment, surgical patients exhibited improvements in physical health and reductions in lung cancer symptoms following initial deterioration within the first two months; in contrast, SBRT patients showed persistent decline in these areas throughout the year. Nonetheless, improved mental health was noted across both patient categories post-treatment. Targeted interventions and continuous monitoring are recommended during the initial 2 months post-surgery and throughout the year post-SBRT to alleviate physical and mental distress in patients.

Outcomes in Incidentally Versus Screening Detected Stage I Lung Cancer Surgery Patients.

INTRODUCTION: Although the importance of lung cancer screening for early diagnosis is established, because of poor enrollment, incidental findings still play a role in diagnosis of patients who qualify. Nevertheless, analysis of this incidental cohort is lacking. We present a retrospective analysis comparing patients with thoracic surgery with incidental versus screening detected stage I lung cancer. METHODS: Thoracic surgery cases at Mount Sinai Hospital from March, 1, 2012, to June, 30, 2022, were queried for patients eligible for lung cancer screening and a stage I diagnosis. The basis of lung nodule detection (incidental versus screening detected) was identified. We compared demographic variables, comorbidities, tumor staging, procedure details, and postoperative outcomes between the cohorts. RESULTS: Of the patients eligible for screening with lung cancer resection and stage I diagnosis at Mount Sinai, 153 were identified incidentally and 67 through screening. The patients in the incidental cohort were older (p = 0.005), more likely to have quit smoking (p = 0.04), and had a greater number of comorbidities (p = 0.0002). There was no statistically significant difference between the groups with regard to pack-year smoking history, lung cancer histological type, location or size of tumor, and surgical approach, length of surgery or stay, number of postoperative outcomes, and survival. CONCLUSIONS: In stage I lung cancers, no significant differences were identified between incidentally and screening detected lung nodules with regard to tumor characteristics, surgical approach, and postoperative outcomes. Imaging conducted for other reasons should be considered as a valid and important diagnostic tool, similar to traditional low-dose computed tomography, in patients who qualify for screening.

Prospective Cohort Study to Compare Long-Term Lung Cancer-Specific and All-Cause Survival of Clinical Early Stage (T1a-b; ≤20 mm) NSCLC Treated by Stereotactic Body Radiation Therapy and Surgery.

INTRODUCTION: We aimed to compare outcomes of patients with first primary clinical T1a-bN0M0 NSCLC treated with surgery or stereotactic body radiation therapy (SBRT). METHODS: We identified patients with first primary clinical T1a-bN0M0 NSCLCs on last pretreatment computed tomography treated by surgery or SBRT in the following two prospective cohorts: International Early Lung Cancer Action Program (I-ELCAP) and Initiative for Early Lung Cancer Research on Treatment (IELCART). Lung cancer-specific survival and all-cause survival after diagnosis were compared using Kaplan-Meier analysis. Propensity score matching was used to balance baseline demographics and comorbidities and analyzed using Cox proportional hazards regression. RESULTS: Of 1115 patients with NSCLC, 1003 had surgery and 112 had SBRT; 525 in I-ELCAP in 1992 to 2021 and 590 in IELCART in 2016 to 2021. Median follow-up was 57.6 months. Ten-year lung cancer-specific survival was not significantly different: 90% (95% confidence interval: 87%-92%) for surgery versus 88% (95% confidence interval: 77%-99%) for SBRT, p = 0.55. Cox regression revealed no significant difference in lung cancer-specific survival for the combined cohorts (p = 0.48) or separately for I-ELCAP (p = 1.00) and IELCART (p = 1.00). Although 10-year all-cause survival was significantly different (75% versus 45%, p < 0.0001), after propensity score matching, all-cause survival using Cox regression was no longer different for the combined cohorts (p = 0.74) or separately for I-ELCAP (p = 1.00) and IELCART (p = 0.62). CONCLUSIONS: This first prospectively collected cohort analysis of long-term survival of small, early NSCLCs revealed that lung cancer-specific survival was high for both treatments and not significantly different (p = 0.48) and that all-cause survival after propensity matching was not significantly different (p = 0.74). This supports SBRT as an alternative treatment option for small, early NSCLCs which is especially important with their increasing frequency owing to low-dose computed tomography screening. Furthermore, treatment decisions are influenced by many different factors and should be personalized on the basis of the unique circumstances of each patient.

Urinary glyphosate levels and association with mortality in the 2013-16 National Health and Nutrition Examination Survey.

OBJECTIVES: Glyphosate is the most commonly used herbicide in the USA; however, its safety is still under debate. We assessed glyphosate levels and their association with overall mortality in a representative sample of the US adult population from the 2013 to 2016 National Health and Nutrition Examination Survey. METHODS: We extracted data on urinary glyphosate (N = 2910) measured by ion chromatography isotope-dilution tandem mass spectrometry. Associations between glyphosate concentrations and demographic, lifestyle and other exposures were analyzed. Data were linked to public-use Mortality Files for 2019. RESULTS: The mean (STD) glyphosate level was 0.53 (0.59) ng/ml, with 25.7% of the subjects having glyphosate levels at or below the detection limit. At multivariate analysis, age and creatinine were associated with glyphosate urinary levels (both P < 0.0001). There was a borderline association between glyphosate levels and mortality (HRadj 1.33; 95% CI 0.99-1.77 P = 0.06). When 3,5,6-trichloropyridinol was excluded from the Cox model, glyphosate exhibits a significant association with mortality (HRadj 1.33; 95% CI 1.00-1.77; P = 0.0532). CONCLUSIONS: These nationally representative data suggest that recent exposure to glyphosate could be associated with increased mortality. More studies are necessary to understand population-level risk associated with the product, given its widespread use in agriculture.

World Trade Center Exposure, DNA Methylation Changes, and Cancer: A Review of Current Evidence.

Introduction: Known carcinogens in the dust and fumes from the destruction of the World Trade Center (WTC) towers on 9 November 2001 included metals, asbestos, and organic pollutants, which have been shown to modify epigenetic status. Epigenome-wide association analyses (EWAS) using uniform (Illumina) methodology have identified novel epigenetic profiles of WTC exposure. Methods: We reviewed all published data, comparing differentially methylated gene profiles identified in the prior EWAS studies of WTC exposure. This included DNA methylation changes in blood-derived DNA from cases of cancer-free "Survivors" and those with breast cancer, as well as tissue-derived DNA from "Responders" with prostate cancer. Emerging molecular pathways related to the observed DNA methylation changes in WTC-exposed groups were explored and summarized. Results: WTC dust exposure appears to be associated with DNA methylation changes across the genome. Notably, WTC dust exposure appears to be associated with increased global DNA methylation; direct dysregulation of cancer genes and pathways, including inflammation and immune system dysregulation; and endocrine system disruption, as well as disruption of cholesterol homeostasis and lipid metabolism. Conclusion: WTC dust exposure appears to be associated with biologically meaningful DNA methylation changes, with implications for carcinogenesis and development of other chronic diseases.

A 20-year Follow-up of the International Early Lung Cancer Action Program (I-ELCAP).

Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.

Blood inflammatory markers and mortality in the US population: A Health and Retirement Survey (HRS) analysis.

A potential direct correlation between systemic inflammation and physiological aging has been suggested, along with whether there is a higher expression of inflammatory markers in otherwise healthy older adults. Cross-sectional data were extracted from the publicly available 2016 Health and Retirement Survey, a nationally representative survey of older adults in the United States. A subset of participants (n = 9934) consented to a blood draw at the time of recruitment and were measured for high sensitivity C-reactive protein (hs-CRP), Interleukin (IL-6, IL-10, IL-1RA), soluble tumor necrosis factor receptor (sTNFR-1) and transforming growth factor beta 1 (TGF-ß1). We included 9,188 participants, representative of 83,939,225 nationally. After adjusting for sex and the number of comorbidities, there remained a significant positive correlation between age and ln (log adjusted) IL-6, and ln sTNFR-1, and a significant inverse correlation between age and ln IL-1RA, ln TGF-ß1, and ln hs-CRP. Among the subset of participants who reported none of the available comorbidities (n = 971), there remained an independent correlation of age with ln IL-6 and ln sTNFR-1. After adjusting for age, sex, and number of reported comorbidities, there was a statistically significant correlation between increased ln IL-6, ln IL-10, ln sTNFR-1, and ln hs-CRP with death. This study highlights the existence of a correlation between serum biomarkers of inflammation and aging, not only in the whole population, but also in the smaller subset who reported no comorbidities, confirming the existence of a presence of low-grade inflammation in aging, even in healthy elders. We also highlight the existence of a correlation between inflammatory markers and overall mortality. Future studies should address a possible threshold of systemic inflammation where mortality significantly increases, as well as explore the effectiveness of anti-inflammatory treatments on morbidity and mortality in healthy aging subjects.

Personal and clinical characteristics associated with immunotherapy effectiveness in stage IV non-small cell lung cancer.

Background: Immunotherapy response rates in metastatic non-small cell lung cancer (NSCLC) are low and survival varies significantly. Factors like age, sex, race, and histology may modulate immunotherapy response. Existing analyses are limited to clinical trials, with limited generalizability, and meta-analyses where adjustment for potential confounders cannot be performed. Here, we conduct a cohort study with patient-level analysis to explore how personal and clinical characteristics moderate chemoimmunotherapy effectiveness in metastatic NSCLC. Methods: Stage IV NSCLC patients diagnosed in 2015 were drawn from Surveillance Epidemiology, and End Results-Medicare linked data. Receipt of chemoimmunotherapy and overall survival (OS) were the primary predictor and outcome of interest respectively. Multivariable Cox-proportional hazards regression and propensity-score matching were performed to evaluate the effectiveness of immunotherapy addition to chemotherapy. Results: From a total of 1,471 patients, 349 (24%) received chemoimmunotherapy and 1,122 (76%) received chemotherapy alone. Survival was significantly better among those treated with chemoimmunotherapy compared to those receiving chemotherapy alone [adjusted hazard ratio (HRadj) =0.72, 95% confidence interval (CI): 0.63-0.83]. Males saw significantly better OS from chemoimmunotherapy (HRadj =0.62, 95% CI: 0.51-0.75) than females (HRadj =0.81, 95% CI: 0.65-1.01, Pinteraction=0.0557). After propensity-score matching, the effect of chemoimmunotherapy was borderline significant according to sex (Pinteraction =0.0414), but not age or histology. Conclusions: Males may benefit more from chemoimmunotherapy, but there is limited evidence suggesting age, histology, race, and comorbidities contribute to differences in effectiveness. Future research should elucidate who responds best to chemoimmunotherapy, and further analyses of characteristics like race can inform how to tailor different treatment regimens to distinct patient subpopulations.

Surgical markup in lung cancer resection, 2015-2020.

Objective: The objective of this study was to assess procedure markup (charge-to-cost ratio) across lung resection procedures and examine variability by geographic region. Methods: Provider-level data for common lung resection operations was obtained from the 2015 to 2020 Medicare Provider Utilization and Payment Data datasets using Healthcare Common Procedure Coding System codes. Procedures studied included wedge resection; video-assisted thoracoscopic surgery; and open lobectomy, segmentectomy, and mediastinal and regional lymphadenectomy. Procedure markup ratio and coefficient of variation (CoV) was assessed and compared across procedure, region, and provider. The CoV, a measure of dispersion defined as the ratio of the SD to the mean, was likewise compared across procedure and region. Results: Median markup ratio across all procedures was 3.56 (interquartile range, 2.87-4.59) with right skew (mean, 4.13). Median markup ratio was 3.59 for lymphadenectomy (CoV, 0.51), 3.13 for open lobectomy (CoV, 0.45), 3.55 for video-assisted thoracoscopic surgery lobectomy (CoV, 0.59), 3.77 for segmentectomy (CoV, 0.74), and 3.80 for wedge resection (CoV, 0.67). Increased beneficiaries, services, and Healthcare Common Procedure Coding System score (total) were associated with a decreased markup ratio (P < .0001). Markup ratio was highest in the Northeast at 4.14 (interquartile range, 3.09-5.56) and lowest in the South (Markup ratio 3.26; interquartile range, 2.68-4.02). Conclusions: We observe geographic variation in surgical billing for thoracic surgery.

Longitudinal Assessment of Association Between Tobacco Use and Tobacco Dependence Among Adults: Latent Class Analysis of the Population Assessment of Tobacco and Health Study Waves 1-4.

INTRODUCTION: With increasing tobacco product varieties, understanding tobacco use (TU) profiles and their associations with tobacco dependence (TD) has also become increasingly challenging. AIMS AND METHODS: We aimed to identify TU profiles and their associations with TD over time, and to identify subgroups with high risk of TD. We included 3463 adult recent tobacco users who had complete TU and TD data across waves 1-4 of the Population Assessment of Tobacco and Health (PATH) study. We used a composite index of TD and a summed TD score from an established 16-item TD measure. We applied a latent class analysis to identify TU profiles based on participants' usage of eight common tobacco product groups at each survey wave and to check the stability of the TU profiles over time. We then used generalized estimating equations regressions to evaluate the longitudinal TU-TD association, adjusting for potential confounders. RESULTS: We identified three distinct TU profiles that remained consistent across four survey waves: Dominant cigarette users (62%-68%), poly users with high propensity of using traditional cigarettes, e-cigarettes, and cigars (24%-31%), and dominant smokeless product users (7%-9%). Covariate-adjusted models showed that TD was significantly lower among the poly users and the dominant smokeless users, compared to that among the dominant cigarette users. CONCLUSIONS: Both TU profiles and their associations with TD were stable over time at the population level. Poly users and smokeless product users were consistently associated with lower TD than cigarette-dominant users, suggesting the need for tailored tobacco cessation interventions for users with different TU profiles. IMPLICATIONS: The finding of consistent TU profiles across four survey waves extends the current literature in capturing TU patterns in an evolving tobacco product landscape. The finding of the overall higher level of TD among the cigarette-dominant users compared to the other TU latent profiles (the Cig+eCig+Cigar dominant poly users and the dominant smokeless product users) can help identify high-risk groups for potential interventions. Our application of innovative statistical methods to high-quality longitudinal data from the PATH study helps improve the understanding of the dynamic TU-TD relationship over time.

Unequal racial distribution of immunotherapy for late-stage non-small cell lung cancer.

Immunotherapy has increased survival for non-small cell lung cancer (NSCLC), especially for those diagnosed with late-stage disease. However, it is not known if its use is equally distributed across races. We assessed immunotherapy use in 21 098 pathologically confirmed stage IV NSCLC patients according to race in the Surveillance Epidemiology, and End Results-Medicare linked dataset. Multivariable models were conducted to evaluate the independent association of receipt of immunotherapy with race and overall survival according to race. Black patients had statistically significantly lower odds of receiving immunotherapy (adjusted odds ratio = 0.60, 95% confidence interval = 0.44 to 0.80); receipt of immunotherapy was lower in Asian and Hispanic patients but not statistically significant. When immunotherapy was received, survival was similar across races. Immunotherapy for NSCLC is not used equally among races, underscoring the racial disparities that exist in access to the newest cancer treatment. Efforts should be directed toward expanding access to novel, efficacious treatments for advanced stage lung cancer.

Effect of stage shift and immunotherapy treatment on lung cancer survival outcomes.

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.

Assessing how lung cancer screening guidelines contribute to racial disparities in screening access.

Background: Lung cancer (LC) is the leading cause of cancer-related deaths in the United States (U.S.), with non-White people who smoke often bearing the burden of the highest rate of LC mortality. This is often due to later stage diagnoses, leading to poor prognosis and outcomes. We assess here how the eligibility criteria for LC screening set by the U.S. Preventive Services Task Force (USPSTF) and the Centers for Medicare and Medicaid Services (CMS) could contribute to racial disparities in screening access. Methods: This paper analyzes data from the National Health and Nutrition Examination Survey (NHANES), an annual survey conducted by the Centers for Disease Control and Prevention (CDC) that gathers health and nutrition data from a representative sample of the U.S. population. After excluding those who were ineligible for LC screening, the final cohort of participants was 5,001, which consisted of 2,669 people who formerly smoked and 2,332 people who currently smoke. Results: Out of 608 participants who were eligible for LC screening, 77.5% were non-Hispanic White (NHW) and 8.7% were non-Hispanic Black (NHB) participants versus 69.4% and 10.8% among 4,393 ineligible participants. Age, pack-years, and age along with pack-years were the most frequent reasons for ineligibility. LC screening ineligible NHW participants were statistically significantly older and had higher mean pack-years than the other racial and ethnic groups. NHB participants among the ineligible group had higher urinary cotinine levels compared to NHW participants. Conclusions: This paper underscores the need for more individualized risk estimates when determining eligibility for LC screening, which could include biomarkers of smoking exposure. The analysis shows that current screening criteria, which rely solely on factors such as age and pack years, contribute to LC racial disparities.

TERT and BRAF V600E mutations in thyroid cancer of World Trade Center Responders.

The 2-fold excess thyroid cancer risk reported in multiple World Trade Center (WTC) disaster exposed cohorts cannot entirely be explained by surveillance and physician bias thus highlighting the need to investigate the potential consequences of the dust exposure, containing carcinogenic and endocrine disruptive elements, on the thyroid. This study investigated the presence of TERT promoter and BRAF V600E mutations in 20 WTC-exposed versus 23 matched non-exposed thyroid cancers as potential mechanism explaining the excess risk. Although no significant difference in BRAF V600E mutation was found, TERT promoter mutations were significantly more prevalent in WTC thyroid cancer versus non-exposed thyroid cancers (P = 0.021). The odds of a TERT promoter mutation was significantly higher in the WTC versus the non-WTC thyroid cancers after adjustment [ORadj: 7.11 (95% CI: 1.21-41.83)]. These results may indicate that exposure to the mixture of pollutants present in the WTC dust resulted in an excess thyroid cancer risk and potentially more aggressive thyroid cancer, warranting investigating WTC responders on thyroid-associated symptoms during their health checkups. Future studies should include long-term follow-up to provide important insights in whether thyroid-specific survival is negatively affected by WTC dust exposure and whether this is because of the presence of one or more driver mutations.

Trends in prostate cancer incidence among Black men in the Caribbean and the United States.

BACKGROUND: Prostate cancer incidence is highest for Black men of the African diaspora in the United States and Caribbean. Recent changes in recommendations for prostate cancer screening have been shown to decrease overall prostate cancer incidence and increase the likelihood of late stage disease. However, it is unclear how trends in prostate cancer characteristics among high risk Black men differ by geographic region during the changes in screening recommendations. METHODS: In this study, we used population-based prostate cancer registry data to describe age-adjusted prostate cancer incidence trends from 2008 to 2015 among Black men from six geographic regions. We obtained data on incident Black prostate cancer patients from six cancer registries (in the United States: Florida, Alabama, Pennsylvania, and New York; and in the Caribbean: Guadeloupe and Martinique). After age standardization, we used descriptive analyses to compare the demographics and tumor characteristics by cancer registry site. The Joinpoint regression program was used to compare the trends in incidence by site. RESULTS: A total of 59,246 men were analyzed. We found the highest incidence rates (per 100,000) for prostate cancer in the Caribbean countries (181.99 in Martinique and 176.62 in Guadeloupe) and New York state (178.74). Incidence trends decreased significantly over time at all sites except Martinique, which also showed significantly increasing rates of late stage (III/IV) and Gleason score 7+ tumors. CONCLUSIONS: We observed significant differences in prostate cancer incidence trends among Black men after major changes prostate screening recommendations. Future studies will examine the factors that differentially influence prostate cancer trends among the African diaspora.

Malignant pleural mesothelioma characteristics and outcomes: A SEER-Medicare analysis.

BACKGROUND: Pleural mesothelioma is rare cancer linked to asbestos exposure. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. MATERIALS AND METHODS: Malignant pleural mesothelioma cases diagnosed from 1992 to 2015 were queried from the linked SEER-Medicare database. Multivariable logistic regression was used to assess the clinical and demographic factors associated with sex. A multivariable Cox proportional hazards model and propensity matching methods were used to assess sex differences in overall survival (OS) while accounting for potential confounders. RESULTS: Among 4201 patients included in the analysis, 3340 (79.5%) were males and 861 (20.5%) females. Females were significantly older, with more epithelial histology than males were, and had significantly better OS, adjusted for confounders (adjusted hazard ratio, 0.83, 95% confidence interval: 0.76-0.90). Other variables independently associated with improved survival included younger age at diagnosis, having a spouse/domestic partner, epithelial histology, lower comorbidity score, and receipt of surgery or chemotherapy. CONCLUSIONS: The study describes sex differences in mesothelioma occurrence, treatment, and survival and is the first to examine SEER-Medicare. It provides directions for future research into potential therapeutic targets.

Non-asbestiform elongate mineral particles and mesothelioma risk: Human and experimental evidence.

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.

Epidemiologic roadblocks in studying elongated mineral particles and mesothelioma risk.

Elongated mineral particles (EMPs) are a type of both occupational and environmental exposures that have generated interest in the scientific community due to their potential health effects. Their possible association with mesothelioma represents an area of concern. We provide an overview of the current challenges around epidemiological assessments of EMP exposure and mesothelioma risk, including methodological aspects that need to be addressed when designing and analyzing a study on EMP exposure and mesothelioma. Future work is needed to investigate the relationship between EMPs and mesothelioma, focused on an improved definition of EMP exposure and accounting for other concomitant sources of carcinogen exposure.