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The collapse of the World Trade Center (WTC) buildings in New York City generated a large plume of dust and smoke. WTC dust contained human carcinogens including metals, asbestos, polycyclic aromatic hydrocarbons (PAHs), persistent organic pollutants (POPs, including polychlorinated biphenyls (PCBs) and dioxins), and benzene. Excess levels of many of these carcinogens have been detected in biological samples of WTC-exposed persons, for whom cancer risk is elevated. As confirmed in this structured literature review (n studies = 80), all carcinogens present in the settled WTC dust (metals, asbestos, benzene, PAHs, POPs) have previously been shown to be associated with DNA methylation dysregulation of key cancer-related genes and pathways. DNA methylation is, therefore, a likely molecular mechanism through which WTC exposures may influence the process of carcinogenesis.

Purpose: To assess the association between food insecurity and colorectal cancer screening uptake in screening eligible participants in New York State., Methods: We analyzed 28,154 adults who participated in New York State Behavioral Risk Factor Surveillance System (BRFSS) from 2018 to 2021, were age-eligible for colorectal cancer screening based on the USPSTF guidelines at the time of survey administration and answered a version of the administered survey that included the module on food insecurity. Participants were defined as food insecure if they self-reported being always, usually, or sometimes stressed about having enough money to buy nutritious meals in the past 12 months. We compared demographic, healthcare access, overall health status, food insecurity by colorectal cancer screening status. Multivariable analyses were performed to assess the association of food insecurity and colorectal cancer screening status after adjusting for relevant covariates. Weighted analyses were performed using survey procedures to obtain population estimates., Results: Food insecurity was statistically significantly associated a decreased likelihood of being up to date on colorectal cancer screening (OR adj 0.83, 95% CI [0.72, 0.94]) and being ever screened for colorectal cancer (OR adj 0.74, 95% CI [0.64, 0.87]) after adjusting for overall health status, healthcare coverage, interview year, age, race/ethnicity, sex, educational attainment, and income. Health status, health coverage, age, and Non-Hispanic Black race/ethnicity showed positive, statistically significant association with ever being screened and with being up to date for colorectal cancer screening. Lower income, lower educational attainment, and non-Hispanic Asian race/ethnicity were statistically significant inverse predictors of ever being screened and being up to date on screening., Conclusion: This project assessed the association between food insecurity and colorectal cancer screening uptake using the BRFSS survey. Food insecurity may be an important predictor for colorectal cancer screening uptake in eligible adults in the United States. The results from the study can inform future interventions and policies designed to improve participation in routine colorectal cancer screening., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Surgery has been the standard procedure for resectable primary LC. Survival after stereotactic body radiation therapy, another treatment, is significantly biased due to preponderance of data from patients deemed unsuitable for surgery. We examined survival of patients refusing surgery in favor of radiation therapy., Methods: We used the Surveillance, Epidemiology, and End Results database to identify patients with primary Stage I NSCLC diagnosed between 2007 and 2016. Patients were excluded if it was unknown if they were recommended for surgery or if surgery was contraindicated. Multiple predictors were assessed: radiation versus surgery, age at diagnosis, sex, race/ethnicity, health insurance status, marital status, tumor size, and histology. A multivariate analysis was performed to estimate hazard ratios and generate Kaplan-Meier survival curves., Results: When adjusted for confounding variables, survival was greater for patients undergoing surgical resection than those refusing surgery in favor of radiation (HR adj 2.66; 95% CI: 2.27-3.11, p < 0.001) or for those receiving no standardized treatment (HR adj 4.43; 95% CI: 3.57-5.50, p < 0.001)., Conclusions: SBRT is an effective treatment for inoperable early LC but there is limited data comparing outcomes against surgical resection. When eligible for both, patients refusing surgery and choosing radiation had worse survival when adjusting for variables including age, tumor size, and histology, and suggests that surgical resection is a superior treatment modality., (© 2024 Wiley Periodicals LLC.)

Background: Precision therapies, such as targeted and immunotherapies, have substantially changed the landscape of late-stage non-small cell lung cancer (NSCLC). Yet utilization of these therapies is disproportionate across strata defined by race and socioeconomic status (SES), possibly due to disparities in molecular diagnostic testing (or "biomarker testing"), which is a prerequisite to treatment., Methods: We extracted a cohort of NSCLC patients from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. The primary outcome was receipt of a molecular diagnostic test, based on claims data. The primary predictors were race and SES. Likelihood of receiving a molecular diagnostic test, and overall survival (OS), were investigated using logistic and Cox proportional hazards regression, adjusted for sex, age, residence, histology, marital status, and comorbidity., Results: Of the 28,511 NSCLC patients, 11,209 (39.3%) received molecular diagnostic testing. Compared to White patients, fewer Black patients received a molecular diagnostic test (40.4% vs 27.9%; p < .001). After adjustment, Black patients (ORadj [odds ratio]: 0.64; 95% CI [confidence interval]: 0.58-0.71) and those living in areas with greater poverty (ORadj: 0.85; 95% CI: 0.80-0.89) had statistically significant decreased likelihood of molecular diagnostic testing. Patients who did receive testing had a statistically significant decreased risk of death (HRadj [hazards ratio]: 0.74; 95% CI: 0.72-0.76). These results held in the stratified analysis of stage IV NSCLC patients., Conclusion: Disparities exist in comprehensive molecular diagnostics, which is critical for clinical decision making. Addressing barriers to molecular testing could help close gaps in cancer care and improve patient outcomes., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Human papillomavirus (HPV)+ oropharynx cancer (OPC) has a more favorable prognosis than HPV-negative disease, but the impact of specific HPV genotype and phylogenic clade on patient outcomes is not well understood and has profound implications for treatment de-intensification., Methods: The objective of this single-institution cohort study was to investigate the association of HPV genotype (16 vs high-risk non-16) and clade (A9 vs A7) with OPC outcomes. The primary endpoints were overall survival (OS) and event-free survival (EFS) in patients with M0 disease treated with curative intent., Results: The cohort included 598 patients (87% HPV16, 98% A9). Compared to those with HPV16 OPC, individuals with non-HPV16 OPC had a higher age, comorbidity index, and proportion of non-whites, HIV+ patients, T4 tumors, and stage IV disease (AJCC 7th edition). Non-HPV16 genotype was associated with worse OS in univariate (HR = 2.17, 95% CI, 1.24-3.80, P = .0066), but not in multivariate analysis (HRadj = 0.84, 95% CI, 0.43-1.62, P = .5921). A7 clade was associated with worse OS in univariate (HR = 4.42, 95% CI, 1.60-12.30, P = .0041), but not in multivariate analysis (HRadj = 2.39, 95% CI, 0.57-9.99, P = .2325). Neither HPV genotype (HR = 1.60, 95% CI, 0.99-2.60, P = .0566) nor phylogenic clade (HR = 2.47, 95% CI, 0.91-6.72, P = .0761) was associated with EFS., Conclusion: Non-HPV16 genotype and A7 clade were associated with worse OS and trended toward worse EFS in univariate analyses. The survival differences were more pronounced by phylogenic clade than by HPV16 status, suggesting that the former may be a more useful classification for future studies. However, neither HPV16 status nor phylogenic clade was prognostic when adjusting for patient and tumor covariates, raising the question as to whether possible differences in outcomes are related to distinct clinical profiles rather than inherent viral properties., (Published by Oxford University Press 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: To facilitate global implementation of lung cancer (LC) screening and early detection in a quality assured and consistent manner, common terminology is needed. Researchers and clinicians within different specialties may use the same terms but with different meanings or different terms for the same intended meanings., Methods: The Diagnostics Working Group of the International Association for the Study of Lung Cancer Early Detection and Screening Committee has analyzed and discussed relevant terms used on a regular basis and suggests recommendations for consensus definitions of terminology applicable in this setting. We explored how to reach consensus to define relevant and unambiguous terminology for use by health care providers, researchers, patients, screening participants, and family., Results: Terms and definitions for epidemiologic and health-economical purposes included the following: standardized incidence and mortality rates, LC-specific survival, long-term survival and cure rates, overdiagnosis, overtreatment, and undertreatment. Terms and definitions for defining screening findings included the following: positive, false-positive, negative, false-negative, and indeterminate findings and additional and incidental findings. Terms and definitions for describing parameters in screening programs included the following: opportunistic versus programmatic screening, screening rounds, interval or interim diagnoses, and invasive and minimally invasive procedures. Terms and definitions for shared decision-making included the following: LC screening-possible harms and risks and LC risk and modifiers prior and posterior to a measure., Conclusions: A common set of terminology with standard definitions is recommended for describing clinical LC screening programs, the discussion about effectiveness and outcomes, or the clinical setting. The use of the terms should be clearly defined and explained., Competing Interests: Disclosure Dr. Huber participated in advisory boards for Janssen Germany, Merck Germany, Boehringer Ingelheim, Sanofi Germany, Novocure Germany Advisory, is deputy chair of the Early detection and screening committee of IASLC and co-chair of the ERS/ESTS task force Fitness for therapy of lung cancer. Dr. Kitts gets consulting fees from City of Hope, American College of Radiology and Memorial Sloan Kettering and support for attending meetings from Rescue Lung Society and American Cancer Society. Dr. Kitts has patents for Community based Individualized Health Platforms and Individualized Health Platforms, issued to Prosumer Health Founders and leadership roles in Rescue Lung Society, Lung Cancer Policy Network and Prosumer Health (start-up company) and stocks of Johnson & Johnson, Abbvie and Abbot Labs. Dr. Henschke serves on advisory board for Lunglife AI. without compensation and is a named inventor on a number of patents and patent applications relating to the evaluation of pulmonary nodules on CT scans of the chest which are owned by Cornell Research Foundation (CRF). Since 2009, Dr. Henschke does not accept any financial benefit from these patents including royalties and any other proceeds related to the patents or patent applications owned by CRF. Dr. Henschke is the President and serves on the board of the Early Diagnosis and Treatment Research Foundation. She receives no compensation from the Foundation. The Foundation is established to provide grants for projects, conferences, and public databases for research on early diagnosis and treatment of diseases. Recipients include, I-ELCAP, among others. The funding comes from a variety of sources including philanthropic donations, grants and contracts with agencies (federal and non-federal), imaging and pharmaceutical companies relating to image processing assessments. The various sources of funding exclude any funding from tobacco companies or tobacco-related sources. Dr. Lam got travel support from IASLC to attend World Conference on Lung Cancer and from the Canadian Partnership Against Cancer and is on its advisory aboard as well as for Nucleix Technologies Inc Medical. Dr. Kazerooni is on the advisory board of the International Lung Screening Trial. Dr. Kerpel-Fronius is on the speaker bureau of Boehringer Ingelheim and MSD. Dr. Yankelevitz owns equity in HeartLung and is on advisory boards for HeartLung, Median Technology, Carestream and Lunglife AI. Dr. Yankelevitz is a named inventor on a number of patents and patent applications related to the evaluation of chest diseases including measurements of chest nodules. Dr. Yankelevitz has received financial compensation for the licensing of these patents. He is consultant and co-owner of Accumetra. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Multi-cancer early detection (MCED) tests are blood-based tests designed to screen for signals of multiple cancers. There is growing interest and investment in examining the potential benefits and applications of MCED tests. If MCED tests are shown to have clinical utility, it is important to ensure that all people-regardless of their demographic or socioeconomic background-equitably benefit from these tests. Unfortunately, with health care innovation, such considerations are often ignored until after inequities emerge. We urge for-profit companies, scientists, clinicians, payers, and government agencies to prioritize equity now-when MCEDs are still being developed and researched. In an effort to avoid creating and exacerbating cancer inequities, we propose 9 equity considerations for MCEDs., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2024. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

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., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

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-12 v2 ) [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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1201/coif). All authors report that this study was supported by generous grants from the Simons Foundation (International, Ltd.). D.F.Y. is a named inventor on a number of patents and patent applications related to the evaluation of chest diseases including measurements of chest nodules. D.F.Y. has received financial compensation for the licensing of these patents. In addition, he is a consultant and co-owner of Accumetra, a private company developing tools to improve the quality of CT imaging. He is on the advisory board and owns equity in HeartLung, a company that develops software related to CT scans of the chest. He is on the medical advisory board of Median Technology that is developing technology related to analyzing pulmonary nodules and is on the medical advisory board of Carestream, a company that develops radiography equipment. C.I.H. is also an inventor of the patents and pending patents owned by Cornell Research Foundation. As of April 2009, she has divested herself of all royalties and other interests arising from these. She is on the medical advisory board for LungLife Al. The authors have no other conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: In patients with non-small cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs) are an effective mode of treatment. Despite their efficacy, responses to ICIs have been shown to differ based on several factors; for example, antibiotic use prior to and/or during immunotherapy has been associated with lower survival in NSCLC patients. The objective of this study is to provide an updated review of the literature and to fill in important knowledge gaps by accounting for potential confounding in the relationship between ICIs and survival., Methods: We performed a systematic review and meta-analysis on peer-reviewed studies that examined the effects of antibiotic use on overall survival (OS) and progression-free survival (PFS) in NSCLC patients treated with ICIs. We searched MEDLINE for studies published up to June 30 th , 2023 that included NSCLC patients treated with anti-programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) agents, who received antibiotics before and/or during immunotherapy, and included a control group who did not receive antibiotics and had available data on the associations between antibiotics and OS and PFS. We calculated aggregated crude OS and PFS for all studies, and only for studies that reported multivariable hazard ratios (HRs). Risk of bias was assessed using a funnel plot. All results were synthesized and displayed using the metaphor statistical package in R, version 4.2.1., Results: Nineteen studies, conducted between 2017 and 2022, met the inclusion criteria, and included 2,932 patients with advanced and/or metastatic NSCLC. Compared to those who did not receive antibiotics, immunotherapy patients who did had a significantly reduced PFS (HR: 1.22, 95% CI: 1.03-1.44) and OS (HR: 1.56, 95% CI: 1.23-1.99). Adjusted HRs were even more pronounced (OS HR adj : 1.67, 95% CI: 1.23-2.27, PFS HR adj : 1.64, 95% CI: 1.16-2.32)., Conclusions: NSCLC patients treated with antibiotics have significantly lowered survival compared with patients not treated with antibiotics. These results support the hypothesis that antibiotic use in conjunction with ICI among NSCLC patients lowers survival. Limitations of this analysis include the use of studies available only on a single database, limiting the literature search to NSCLC patients, which may impact the generalizability of results to other cancer patient populations, and the inability to account for and adjust the estimates for the same variables (e.g., age, sex) across all studies. Nevertheless, our findings underscore the importance of taking antibiotic use into consideration when using ICIs to treat NSCLC and suggest that confounders should be taken into account when designing future similar studies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-597/coif). The authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

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.

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.

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-β1). 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-β1, 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kalair et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© 2023 Wiley Periodicals LLC.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:JG, SS, BC, DB, AN, and GG have served as experts in asbestos and/or talc litigation. JG and GG are members of the Scientific Advisory Board of NSSGA and received a honorarium for time spent on organizing the conference. They, and most other participants, are grateful to NSSGA for covering travel and accommodation costs. The time spent by the authors in the preparation of this manuscript was at their own expense or of their employers. The National Mesothelioma Virtual Bank (NMVB) section of this workshop summary is funded and supported by the Centers for Disease Control and Prevention (CDC) in association with the National Institute for Occupational Safety and Health (NIOSH) Grant U24OH009077., (Copyright © 2022 Gradco LLC dba Gradient. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 Wiley Periodicals LLC.)

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 (HR adj ) =0.72, 95% confidence interval (CI): 0.63-0.83]. Males saw significantly better OS from chemoimmunotherapy (HR adj =0.62, 95% CI: 0.51-0.75) than females (HR adj =0.81, 95% CI: 0.65-1.01, P interaction =0.0557). After propensity-score matching, the effect of chemoimmunotherapy was borderline significant according to sex (P interaction =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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-682/coif). KHP received $5,500 stipend as part of the Tisch Cancer Institute (TCI) Summer Scholars Program for Icahn School of Medicine’s cancer fellowship to cover living expenses. Funding did not go towards anything other than living expenses. ST is supported by a National Research Services Awards T32 award from the Health Resources and Services Administration and the Agency for Healthcare Research and Quality. National Cancer Institute (NCI) grant P30CA196521 awarded to ET at the Icahn School of Medicine at Mount Sinai. The other author has no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-816/coif). The authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

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., (© 2023 The Author(s).)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) axis (collectively referred to as PD[L]1i) have demonstrated clinical benefits in non-small cell lung cancer (NSCLC) patients. The purpose of this United States-based real-world study is to examine changes in the landscape of first-line therapies for NSCLC since the introduction of PD(L)1i., Methods: Patients with NSCLC initiating first-line treatment between May 1, 2017, and October 31, 2020, were identified in the IBM MarketScan® database. Patients were assigned groups based on first-line therapy: PD(L)1i monotherapy, chemotherapy alone, PD(L)1i with chemotherapy, or targeted therapy for patients with actionable driver mutations., Results: A total of 5431 patients with NSCLC starting first-line treatment were identified: chemotherapy alone 2568 (47%), PD(L)1i with chemotherapy 1364 (25%), PD(L)1i monotherapy 790 (15%), and targeted therapy 709 (13%). The use of PD(L)1i monotherapy and targeted therapy remained consistent, while the percentage of patients receiving PD(L)1i with chemotherapy more than doubled. Over a third of patients in 2019 and 2020 received chemotherapy alone. Patients aged ≥65 years (odds ratio [OR]: 0.80; 95% confidence interval [CI]: 0.68-0.95), females (OR: 0.86; 95% CI: 0.74-0.98), and those with respiratory (OR: 0.82; 95% CI: 0.71-0.94) or kidney (OR: 0.56; 95% CI: 0.40-0.77) disease were less likely to have received PD(L)1i with chemotherapy than patients that received chemotherapy alone., Conclusions: Since the approval of PD(L)1i for NSCLC, their use has significantly increased for first-line treatment, especially when used in combination with chemotherapy. A significant proportion of patients received chemotherapy alone., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Indeterminate lung nodules have been increasingly discovered since the expansion of lung cancer screening programs. The diagnostic approach for suspicious nodules varies based on institutional resources and preferences. The aim of this study is to analyze factors associated with diagnostic modalities used for early-stage non-small cell lung cancer (NSCLC)., Methods: The National Cancer Database was queried for all patients with stage I NSCLC from 2004 to 2015. Four diagnostic modalities were identified, including clinical radiography alone (CRA), bronchial cytology (BC), procedural biopsy (PB), and surgical biopsy (SB). A multivariable multinomial logistic regression was used to assess associations of patient demographics, cancer characteristics, and facility characteristics with these modalities., Results: Of 250,614 patients, 4,233 (1.7%) had CRA, 5,226 (2.1%) had BC, 147,621 (59.9%) had PB, and 93,534 (37.3%) had SB. Older patients were more likely to receive CRA (adjusted odds ratio [ORadj] = 5.3) and less likely to receive SB (ORadj = 0.73). Black patients were less likely to receive SB (ORadj = 0.83) and more likely to receive BC (ORadj = 1.31). Private insurance was associated with SB (ORadj = 1.11), whereas Medicaid was associated with BC (ORadj = 1.21). Patients more than 50 miles from the facility were more likely to undergo SB (ORadj = 1.25 vs PB; ORadj = 1.30 vs CRA; ORadj = 1.38 vs BC). Patients receiving SB had shorter days from diagnosis to treatment (23.0 vs 53.5 to 64.7 for other modalities, P < 0.001)., Conclusions: Diagnostic SB to confirm early-stage NSCLC was associated with younger age, greater travel distance, and shorter time to treatment in comparison with other modalities. Black race and non-private insurance were less likely to be associated with SB.

Objective: Research indicates that greater exposure to Hurricane Sandy is associated with increased mental health difficulties. This study examined whether Project Restoration, a program that linked adults into mental health care (L2C), was effective in reducing post-Sandy mental health difficulties as compared to a cohort of adults matched on mental health difficulties that were not linked into post-Sandy mental health care., Methods: Project Restoration participants (n = 52) with elevated self-reported mental health difficulties had the option to enroll into L2C. Project LIGHT (n = 63) used similar methodologies but did not have a L2C component and served as the matched control group., Results: Multivariable modeling showed significant decreases in all mental health difficulties except for depression in the Project Restoration group, whereas there were no significant decreases in LIGHT. The decrease in anxiety from baseline to follow-up was significantly greater for Project Restoration as compared to LIGHT., Conclusion: Findings confirm the powerful impact community outreach and treatment have on reducing mental health difficulties after a disaster.

Objectives: To determine whether radiographic measures of tumor aggressiveness differ by smoking status., Materials and Methods: 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., Results: 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)]., Conclusion: Smoking history does not influence VDT or PET SUVmax measures of lung cancer aggressiveness., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest.

Background: Patients with cancer are at risk for severe COVID-19. Previous studies examining mortality in cancer patients with COVID-19 have produced inconclusive results. Several published meta-analyses have aimed to estimate this association; however, because of methodological limitations in study selection and data aggregation, these studies do not reliably estimate the independent association between cancer and COVID-19 mortality. We conducted this systematic review and meta-analysis to determine whether cancer is an independent risk factor for COVID-19 mortality., Methods: A literature search was performed in PubMed to identify studies that compared COVID-19 mortality in adult patients with and without cancer. Selection criteria included polymerase chain reaction-confirmed COVID-19, multivariate adjustment and/or matching for mortality risk estimates, and inclusion of hospitalized noncancer controls. Adjusted odds ratios and/or hazard ratios for mortality based on cancer status were extracted. Odds ratio and hazard ratio estimates were pooled using a random effects model., Results: The analysis included 42 studies comprising 129 840 patients: 8612 cancer patients and 121 228 noncancer patients. Of these studies, 18 showed a null difference in survival between cancer and noncancer patients with COVID-19, and 24 studies showed statistically significantly worse survival in cancer patients with COVID-19. Meta-analysis revealed an increased risk of mortality in patients with cancer compared with noncancer patients with COVID-19 (odds ratio = 1.93, 95% confidence interval = 1.55 to 2.41; hazard ratio = 1.54, 95% confidence interval = 1.29 to 1.84)., Conclusion: We conclude that cancer is an independent risk factor for mortality in unvaccinated patients admitted for or diagnosed with COVID-19 during hospitalization., (© The Author(s) 2022. Published by Oxford University Press.)

Background: The role of interferon gamma (IFN-γ) expression in long-term survival has not been studied in patients with urinary bladder cancer (UBC). IFN-γ expression was characterized among various UBC patient cohorts to assess if IFN-γ status is associated with overall survival (OS)., Methods: A tumor-based IFN-γ gene signature was evaluated among adult UBC patients newly diagnosed between 2004 and 2017 from two hospital systems in New York. Patient cohorts included metastatic (stage IV or progressing to stage IV [MBC]), muscle-invasive (stages T2a to T4a [MIBC]), and non-muscle-invasive (carcinoma in situ or stages 0a, 0is, and I [NMIBC]) disease. Descriptive analyses were conducted comparing IFN-γ signature in the highest tertile to those in the lowest two tertiles., Results: 234 patients with bladder cancer were evaluated (56 MBC, 38 MIBC, and 140 NMIBC). Median OS was only reached in the MIBC cohort for those with an IFN-γ signature in the lowest two tertiles (15.03 months [95% CI, 8.50-50.60]). Those with an IFN-γ signature in the highest tertile had a decreased risk of mortality in all cohorts indicating better survival, but this was statistically significant in only the MIBC cohort (adjusted HR = 0.09 [95% CI, 0.01-0.73])., Conclusion: IFN-γ signature status was associated with a decreased mortality risk in all cohorts, particularly MIBC, indicating that it may be a prognostic marker of survival in patients with UBC., Competing Interests: Christina Gillezeau, Maaike van Gerwen and Emanuela Taioli declare no competing interests exist. Naimisha Movva and Jon Fryzek report grants from AstraZeneca. Karma Rabon-Stith, Norah Shire and Philip Zachary Brohawn report employment with AstraZeneca. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Hurricane Sandy made landfall across New York City (NYC) in October 2012, but the long-term consequences of the storm are still not fully understood. We analyzed NYC data to quantify the extent of Hurricane Sandy-related concerns over time., Methods: Data on NYC 311 Call Center inquiries were downloaded from the NYC Open Data website (October 29, 2012 to May 26, 2020) to provide information about Sandy-related calls using the keywords "Hurricane" and "Sandy"., Results: In the first 2 wk after Hurricane Sandy, 15.6% of 311 calls were related to the storm. From 2012 to 2020, the volume of inquiries decreased from 87,209 to 25. The majority of calls in 2012 (49,181; 56%) was requesting general Hurricane Sandy information, and in 2020 assistance with property restoration (20; 79%)., Conclusions: The long-term consequences of Hurricane Sandy in NYC persist into 2020, almost 8 y after the initial event. The needs of Hurricane Sandy victims have changed over time from requiring general information regarding closures, property destruction and immediate disaster relief to aid with legal, financial, and mental health consequences. Disaster response policy-makers must understand the changing needs of NYC residents to provide resources and prepare for future disasters.

The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and less frequently, breast cancer, several types of skin carcinomas, and other tumor types. Mesotheliomas in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy. Others may grow aggressively but very often respond to therapy. Detecting BAP1 germline mutations has, therefore, substantial medical, social, and economic impact. Close monitoring of these patients and their relatives is expected to result in prolonged life expectancy, improved quality of life, and being cost-effective. The co-authors of this paper are those who have published the vast majority of cases of mesothelioma occurring in patients carrying inactivating germline BAP1 mutations and who have studied the families affected by the BAP1 cancer syndrome for many years. This paper reports our experience. It is intended to be a source of information for all physicians who care for patients carrying germline BAP1 mutations. We discuss the clinical presentation, diagnostic and treatment challenges, and our recommendations of how to best care for these patients and their family members, including the potential economic and psychosocial impact., (Copyright © 2022 International Association for the Study of Lung Cancer. All rights reserved.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-191/coif). The authors have no conflicts of interest to declare.

There is increased incidence of prostate cancer (PC) among World Trade Center (WTC)-exposed responders and community members, with preliminary evidence suggestive of more aggressive disease. While previous research is supportive of differences in DNA methylation and gene expression as a consequence of WTC exposure, as measured in blood of healthy individuals, the epigenetics of WTC PC tissues has yet to be explored. Patients were recruited from the World Trade Center Health Program. Non-WTC PC samples were frequency matched on age, race/ethnicity and Gleason score. Bisulfite-treated DNA was extracted from tumor tissue blocks and used to assess global DNA methylation with the MethylationEPIC BeadChip. Differential and pathway enrichment analyses were conducted. RNA from the same tumor blocks was used for gene expression analysis to further support DNA methylation findings. Methylation data were generated for 28 samples (13 WTC and 15 non-WTC). Statistically significant differences in methylation were observed for 3,586 genes; on average WTC samples were statistically significantly more hypermethylated (P = 0.04131). Pathway enrichment analysis revealed hypermethylation in epithelial mesenchymal transition (EMT), hypoxia, mitotic spindle, TNFA signaling via NFKB, WNT signaling, and TGF beta signaling pathways in WTC compared to non-WTC samples. The androgen response, G2M and MYC target pathways were hypomethylated. These results correlated well with RNA gene expression. In conclusion, long-term epigenic changes associated with WTC dust exposure were observed in PC tissues. These occurred in genes of critical pathways, likely increasing prostate tumorigenesis potential. This warrants analysis of larger WTC groups and other cancer types., (Published by Oxford University Press 2022.)

Background: The aim of this ecological study was to assess the area-level relationship between cumulative death rate for COVID-19 and historic influenza vaccination uptake in the New York City population., Methods: Predictors of COVID-19 death included self-reported influenza vaccination in 2017, as well as four CDC-defined risk factors of severe COVID-19 infection available at the ecological level, which were diabetes, asthma, BMI 30-100 ( 2 kg/m2 ) and hypertension, in addition to race and age (65 + years)., Results: After adjusting for potential confounders, for every one-unit increase in influenza vaccination uptake for each zip code area, the rate of COVID-19 deaths decreased by 5.17 per 100,000 residents (p < 0.0001)., Conclusions: Zip codes with a higher prevalence of influenza vaccination had lower rates of COVID-19 mortality, inciting the need to further explore the relationship between influenza vaccination uptake and COVID-19 mortality at the individual level., (© 2022. The Author(s).)

Background: In view of the 2013 American Thyroid Association consensus statement on outpatient thyroidectomy, the present study assessed the trends and factors associated with thyroid cancer surgery setting in older adults, using the New York Statewide Planning and Research Cooperative System database., Materials and Methods: There were 14,495 patients with surgically treated thyroid cancer in New York State between 2007 and 2017. Trends were plotted over time and stratified by surgery type. Significance of the trend was assessed using the Mann-Kendall test. Multivariable logistic regression was used to assess independent associations with surgical setting., Results: The overall outpatient surgery rate significantly increased over time (correlation coefficient 0.82; P < 0.001), for both total thyroidectomy (P < 0.001) and lobectomy (P < 0.001). Factors associated with increased odds of inpatient surgery were medium- and high-volume hospitalization (adjusted odds ratio [OR adj ] 2.12, 95% confidence interval [CI] 1.93-2.32; OR adj 1.69, 95% CI 1.55-1.85, respectively) versus low volume, undergoing total thyroidectomy (OR adj 1.75, 95% CI 1.61-1.90), as well as having Medicare insurance (OR adj 1.13, 95% CI 1.02-1.24) versus private insurance., Conclusions: The present study shows that outpatient thyroidectomy is increasingly favored over inpatient thyroidectomy over time in an older patient population. A clear changepoint following 2011 preceded the publication of the American Thyroid Association statement on outpatient thyroidectomy in 2013 and was likely associated with multiple publications reporting safety of outpatient thyroid surgery and clear economic benefits., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Global efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions of prevention and treatment strategies., Methods: In the United States, the National Cancer Institute in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation's largest coordinated effort to study coronavirus disease 2019. The network comprises multidisciplinary researchers bridging gaps and fostering collaborations among immunologists, epidemiologists, virologists, clinicians and clinical laboratories, social and behavioral scientists, policymakers, data scientists, and community members. In total, 49 institutions form the SeroNet consortium to study individuals with cancer, autoimmune disease, inflammatory bowel diseases, cardiovascular diseases, human immunodeficiency virus, transplant recipients, as well as otherwise healthy pregnant women, children, college students, and high-risk occupational workers (including healthcare workers and first responders)., Results: Several studies focus on underrepresented populations, including ethnic minorities and rural communities. To support integrative data analyses across SeroNet studies, efforts are underway to define common data elements for standardized serology measurements, cellular and molecular assays, self-reported data, treatment, and clinical outcomes., Conclusions: In this paper, we discuss the overarching framework for SeroNet epidemiology studies, critical research questions under investigation, and data accessibility for the worldwide scientific community. Lessons learned will help inform preparedness and responsiveness to future emerging diseases., (© The Author(s) 2022.. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To examine whether hurricane exposure, lack of access to medical care (LAMC), and displacement during Hurricane Sandy were associated with PTSD and other mental health (MH) symptoms among older adult New York residents., Methods: Participants ( N = 411) were ≥60 years old at the time of survey data collection (1-4 years post-Sandy). Outcomes included PTSD, depression, and anxiety symptoms and stress. Hurricane exposure, displacement, and LAMC were primary predictors., Results: Older adults with greater hurricane exposure had increased PTSD, anxiety, and stress symptoms. LAMC had a strong association (ORadj = 4.11) with PTSD symptoms but was not associated with other MH symptoms. Displacement was not associated with MH outcomes., Discussion: This is the first study to examine exposure, displacement, and LAMC together and to examine their varying impacts on different MH outcomes among older adults post-hurricane. Findings support the importance of disaster preparedness interventions tailored to the MH needs of community-dwelling older adults.

Purpose: Racial disparities persist among lung cancer patients but have not been adequately studied among Asian/Pacific Islander (API) subgroups, which are heterogeneous. This study compared clinical and demographic characteristics at diagnosis of API subgroups and NHW patients., Methods: NHW and API adults diagnosed with lung cancer were identified from the Surveillance, Epidemiology, and End Results database (1990-2015). API was divided into eight subgroups: Chinese, Japanese, Filipino, Hawaiian/Pacific Islander, Korean, Vietnamese, Asian Indian/Pakistani, and Other. Multivariable multinomial logistic regression models were used to assess adjusted associations of clinical and demographic factors with API/subgroups., Results: There were 522,702 (92.6%) NHW and 41,479 (7.4%) API lung cancer patients. API were less likely to be diagnosed at the age of ≥ 80 years (OR adj 0.53, 95% CI 0.48-0.58 for ≥ 80 vs. ≤ 39 years) than NHW. However, Japanese patients were more often diagnosed at ≥ 80 years compared to other ethnic subgroups. API were less often female (OR adj 0.85, 95% CI 0.83-0.86), and unmarried (OR adj 0.71, 95% CI 0.68-0.74); however, among API, Japanese, Hawaiian/Pacific Islander, Korean, and Vietnamese were more often unmarried, compared to Chinese patients. API were more frequently diagnosed at stage IV, compared to stage I (OR adj 1.31, 95% CI 1.27-1.35). API had significantly less squamous cell carcinoma (OR adj 0.54, 95% CI 0.52-0.56, compared to adenocarcinoma); among API, Japanese, Filipino, Hawaiian/Pacific Islander, Korean, Asian Indian/Pakistani, and Other were more likely than Chinese patients to present with squamous cell histology (range: OR adj [Other] 1.24, 95% CI 1.09-1.41; OR adj [Hawaiian/Pacific Islander] 2.47, 95% CI 2.22-2.75)., Conclusion: At diagnosis, there are significant differences in demographic and clinical characteristics between NHW, API, and API subgroups. Treating API patients as a single population may overlook biological, environmental, and behavioral differences that might be beneficial in designing prevention strategies and treatment., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Patients with early-stage non-small-cell lung cancer (NSCLC) have high survival rates, but patients often say they did not anticipate the effect of the surgery on their postsurgical quality of life (QoL). This study adds to the literature regarding patient and surgeon interactions and highlights the areas where the current approach is not providing good communication., Design: Since its start in 2016, the Initiative for Early Lung Cancer Research on Treatment (IELCART), a prospective cohort study, has enrolled 543 patients who underwent surgery for stage I NSCLC within the Mount Sinai Health System. Presurgical patient and surgeon surveys were available for 314 patients, postsurgical surveys for 420, and both pre- and postsurgical surveys for 285., Results: Of patients with presurgical surveys, 31.2% said that their surgeon recommended multiple types of treatment. Of patients with postsurgical surveys, 85.0% felt very well prepared and 11.4% moderately well prepared for their postsurgical recovery. The median Functional Assessment of Cancer Therapy-Lung Cancer score and social support score of the patients who felt very well prepared was significantly higher than those moderately or not well prepared (24.0 v. 22.0, P < 0.001) and (5.0 [interquartile range: 4.7-5.0] v. 5.0 [IQR: 4.2-5.0], p = 0.015)., Conclusions: This study provides insight into the areas where surgeons are communicating well with their patients as well as the areas where patients still feel uninformed. Most surgeons feel that they prepare their patients well or very well for surgical recovery, whereas some patients still feel that their surgeons did not prepare them well for postsurgical recovery. Surgeons may want to spend additional time emphasizing postsurgical recovery and QoL with their patients or provide their patients with additional avenues to get their questions and concerns addressed., Highlights: Pretreatment discussions could help surgeons understand patient priorities and patients understand the anticipated outcomes for their surgeries.There is an association between feeling prepared for surgery and higher quality of life and social support scores after adjustment for confounders.Despite these pretreatment discussions, patients still feel that they are not well prepared about what to expect during their postsurgical recovery., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. David Yankelevitz is a named inventor on a number of patents and patent applications related to the evaluation of chest diseases including measurements of chest nodules. Dr. Yankelevitz has received financial compensation for the licensing of these patents. In addition, he is a consultant and co-owner of Accumetra, a private company developing tools to improve the quality of computed tomography imaging, and is on the medical advisory board of Carestream, a company that develops radiography equipment and has consulted for Genentech, AstraZeneca, and Pfizer. Dr. Henschke is also an inventor of the patents and pending patents owned by Cornell Research Foundation (CRF). As of April 2009, she has divested herself of all royalties and other interests arising from these. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided by the Simons Foundation International, Ltd. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. IELCART investigators: Icahn School of Medicine, New York, NY: Raja Flores, Andrew Kaufman, Dong-Seok Lee, Daniel Nicastri, Andrea Wolf, Kenneth Rosenzweig, Jorge Gomez, Mary Beth Beasley, Maureen Zakowski, Michael Chung, David F. Yankelevitz, Claudia Henschke, Emanuela Taioli, Rebecca Schwartz, Huiwen Chan, Jeffrey Zhu, Sydney Kantor, Shana Adler; Mount Sinai West, New York, NY: Daniel Nicastri, Wissam Raad, Pathology: Zrzu Buyuk, Adie Friedman, Ronald Dreifuss, Stacey Verzosa, Mariya Yakubox, Karina Aloferdova, Patricia Stacey, Simone De Nobrega, Jeffrey Zhu, Sydney Kantor, Shana Adler; Mount Sinai Brooklyn, Brooklyn, NY: Ardeshir Hakami, Jeffrey Zhu, Sydney Kantor, Shana Adler; New York University Medical Center, New York, NY: Harvey Pass, Benjamin Cooper, Andre Moreirea, Audrey Sorensen; State University of New York, Syracuse, NY: Leslie Kohman, Robert Dunton, Jason Wallen, Christopher Curtiss, Ernest Scalzetti, Linda Ellinwood; Vassar Brothers, Poughkeepsie, NY: Clifford P. Connery, Emilo Torres, Dan Cruzer, Bruce Gendron, Sonya Alyea, Daniel Lackaye, Lauren Studer; Lahey Hospital, Burlington, MA: Syed Quadri, Elliot Servais, Cameron Stock, Andrea McKee, Brady McKee, Shawn Regis; Northwell Health, New Hyde Park, NY: Paul Lee, Kevin Hyman, Julisa Jurado, David Zeltman, Lawrence Glassman, Rajiv Sharma, Vijay Singh, Efstathia Milhelis, Danielle Gibson; IELCART Coordinating Center: principal investigators (PIs): Raja Flores, Claudia Henschke, co-PIs: Emanuela Taioli, David Yankelevitz, Investigators: Rebecca Schwartz, Betsy Becker, Artit Jirapatnakul, Rowena Yip, Huiwen Chan., (© The Author(s) 2022.)

Background: Although immunotherapy can increase survival in non-small cell lung cancer (NSCLC), response rates are low. It is unclear which characteristics contribute to variability in immunotherapy efficacy and survival. Research is needed to identify reasons for heterogeneity in response rates to better tailor treatments., Methods: Web of Science, Ovid EMBASE, and MEDLINE were queried from 2013 to January 2021, and all studies reporting overall or progression-free survival for patients treated with immunotherapy for NSCLC of at least stage IIIB were screened., Results: Included were 18 randomized controlled trials (RCTs; 6534 immunotherapy RCTs; 11 192 nonimmunotherapy RCTs) and 16 observational studies (n = 9073 immunotherapy patients). Among RCTs, there was improved survival with the addition of immunotherapy in patients aged younger than 65 years in 10 of 17 studies; smokers in 8 of 15 studies; and males in 10 of 17 studies and 6 of 17 females. Only 5 studies reported outcomes by race. Among observational studies, younger patients (aged younger than 60, younger than 65, or younger than 70 years in most studies) had better survival than older patients (aged 60 years and older, 65 years and older, or 70 years and older) in 4 of 13 studies, ever-smokers in 7 of 13, and females in 2 of 14. Three studies reported race with mixed results., Conclusion: Although evidence is mixed, younger patients, smokers, and males may derive more benefit from immunotherapy. Evidence on racial differences is limited. Physicians should be mindful of personal characteristics when formulating treatment plans. Further research is needed to understand underlying mechanisms and to identify the best immunotherapy candidates and alternative treatments for those unlikely to benefit., (© The Author(s) 2022. Published by Oxford University Press.)