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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.)

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 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.

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.)

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: 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.

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.)

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.)

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: 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.)

Rationale: Lung cancer surgical morbidity has been decreasing, increasing attention to quality-of-life measures. A chronic sequela of lung cancer surgery is the use of postoperative oxygen at home after discharge. Prospective studies are needed to identify risk predictors for home oxygen (HO 2 ) use after curative lung cancer surgery. Objectives: To prospectively assess risk factors for postoperative oxygen use and postsurgical morbidity in patients undergoing curative lung cancer surgery. We hypothesized that obesity, poor preoperative pulmonary function, and smoking status would contribute to the risk of postoperative oxygen use. Methods: This study included patients undergoing surgery for a first primary non-small cell lung cancer at Mount Sinai from 2016 to 2020. Univariate, multivariable logistic regression analyses and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were assessed. Results: Of the 433 patients with diagnosed pathologic stage I non-small cell lung cancer, 63 (14.5%) were discharged with HO 2 . By using multivariable analyses, we found that the body mass index (BMI) (OR for a BMI of 25-30 kg/m 2 , 4.0; 95% CI, 1.6-11.2; OR for a BMI ⩾30 kg/m 2 , 6.1; 95% CI, 2.4-17.5) and the preoperative diffusing capacity of the lung for carbon monoxide (Dl CO ) (OR for a Dl CO of <40%, 24.9; 95% CI, 3.6-234.1; OR for a Dl CO of 40-59%,  3.1; 95% CI, 1.3-7.2) were significant independent risk factors associated with the risk of HO 2 use after adjusting for other covariates. Although current smoking significantly increased the risk in the univariate analysis, it was no longer significant in the multivariable model. Conclusions: Obesity and the Dl CO were significant as risk factors for oxygen use at home after discharge. These findings allow for identification of patients at risk of being discharged with HO 2 after lung resection surgery.

Background: It has been postulated that patient's sex impacts response to immunotherapy. Sex modulation of immunotherapy benefit, however, has not yet been explored using patient-level data, where potential confounders, as well as histologic type, can be accounted for. Here we investigated the association between sex and chemoimmunotherapy efficacy for non-small cell lung cancer (NSCLC) using a large, nation-wide dataset., Patients & Methods: Stage IV NSCLC patients diagnosed in 2015 were identified in the National Cancer Database (NCDB). Patients were treated with either chemoimmunotherapy or chemotherapy alone. The efficacy of the addition of immunotherapy treatment by sex was investigated using both an adjusted Cox proportional hazards model and propensity-score matching, in both the overall cohort and stratified by histological subtype., Results: 2064 (16%) patients received chemoimmunotherapy and10,733 (84%) received chemotherapy alone. Adjusted survival analysis in the overall cohort showed that both males (hazards ratio (HR) adj : 0.80, 95% CI: 0.74-0.87) and females (HR adj : 0.83, 95% CI: 0.76-0.90) had better OS when treated with chemoimmunotherapy than chemotherapy alone, with no statistically significant interaction between sex and receipt of immunotherapy (p = 0.63). Propensity matching confirmed these results. However, for those with squamous cell histology, male patients derived more benefit from chemoimmunotherapy treatment than females (HR adj : 0.73, 95% CI: 0.58-0.91 vs HR adj : 1.03, 95% CI: 0.76-1.38; p for interaction = 0.07)., Conclusion: Male patients with squamous cell carcinoma may derive more benefit from chemoimmunotherapy treatment. Histology likely plays an important role in how sex modulates immunotherapy efficacy., (© 2022. The Author(s).)

Importance: Early detection by computed tomography and a more attention-oriented approach to incidentally identified pulmonary nodules in the last decade has led to population stage shift for non-small cell lung cancer (NSCLC). This stage shift could substantially confound the evaluation of newer therapeutics and mortality outcomes., Objective: To investigate the association of stage shift with population mortality among patients with NSCLC., Design, Setting, and Participants: This retrospective cohort study was performed from October 2020 to June 2021 and used data from the Surveillance, Epidemiology, and End Results (SEER) registries to assess all patients from 2006 to 2016 with NSCLC., Main Outcomes and Measures: Incidence-based mortality was evaluated by year-of-death. To assess shifts in diagnostic characteristics, clinical stage and histology distributions were examined by year using χ2 tests. Trends were assessed using the average annual percentage change (AAPC), calculated with JoinPoint software. Kaplan-Meier survival analysis assessed overall survival according to stage and compared those missing any stage with those with a reported stage., Results: The final sample contained 312 382 patients; 166 657 (53.4%) were male, 38 201 (12.2%) were Black, and 249 062 (79.7%) were White; the median (IQR) age was 68 (60-76) years; 163 086 (52.2%) had adenocarcinoma histology. Incidence-based mortality within 5 years of diagnosis decreased from 2006 to 2016 (AAPC, -3.7; 95% CI, -4.1 to -3.4). When assessing stage shift, there was significant association between year-of-diagnosis and clinical stage, with stage I/II diagnosis increasing from 26.5% to 31.2% (AAPC, 1.5; 95% CI, 0.5 to 2.5); and stage III/IV diagnosis decreasing significantly from 70.8% to 66.1% (AAPC, -0.6; 95% CI, -1.0 to -0.2). Missing staging information was not associated with year-of-diagnosis (AAPC, -1.6; 95% CI, -7.4 to 4.5). Year-of-diagnosis was significantly associated with tumor histology (χ2 = 8990.0; P < .001). There was a significant increase in adenocarcinomas: 42.9% in 2006 to 59.0% in 2016 (AAPC, 3.4; 95% CI, 2.9 to 3.9). Median (IQR) survival for stage I/II was 57 months (18 months to not reached); stage III/IV was 7 (2-19) months; and missing stage was 10 (2-28) months. When compared with those with known stage, those without stage information had significantly worse survival than those with stage I/II, with survival between those with stage III and stage IV (log-rank χ2 = 87 125.0; P < .001)., Conclusions and Relevance: This cohort study found an association between decreased mortality and a corresponding diagnostic shift from later to earlier stage. These findings suggest that studies investigating the effect of treatment on lung cancer must take into account stage shift and the confounding association with survival and mortality outcome.

Competing Interests: The authors report no conflicts of interest.

Introduction: Computed tomography (CT) and fluorodeoxyglucose-positron-emission-tomography (FDG-PET) measurements of mediastinal lymph nodes (MLNs) of patients with non-small-cell-lung-cancers (NSCLCs) ≤ 30 mm in maximum diameter are recommended for pre-surgical prediction of MLN metastases., Methods: We reviewed all patients at Mount Sinai Health System enrolled in the Initiative for Early Lung Cancer Research on Treatment (IELCART), prospective cohort between 2016 and 2020, who had pre-surgical FDG-PET and underwent surgery with MLN resection and/or pre-operative endobronchial ultrasound (EBUS) for a first primary NSCLC ≤ 30 mm in maximum diameter on pre-surgical CT., Results: Among 470 patients, none with part-solid (n = 63) or nonsolid (n = 23) NSCLCs had MLN metastases. Solid NSCLCs were identified in 384 patients, none in typical carcinoid (n = 48) or NSCLC ≤ 10 mm in maximum diameter (n = 47, including 8 typical carcinoids) had MLN metastases. Among the remaining 297 patients with solid NSCLCs 10.1-30.0 mm, 7 (2.4%) had MLN metastases. Area-under-the-curve (AUC) for predicting MLN metastases in solid NSCLCs 10.1-30.0 mm, using the CT maximum short-axis MLN diameter was 0.62 (95% CI:0.44-0.81, p = 0.18) and using the highest SUVmax of any MLN, AUC was 0.58 (95% CI:0.39-0.78,p = 0.41). Neither AUCs were significantly different from chance alone. Optimal cutoff for prediction of MLN metastases was ≥ 18.9 mm for CT maximum short-axis diameter [sensitivity 14.3% (95%CI:0.0%-57.9%); specificity 100.0% (95%CI:98.9%-100.0%)] and for highest SUVmax was ≥ 11.7 [sensitivity 14.3% (95%CI:0.0%-57.9%) and specificity 99.7% (95%CI:98.3%-100.0%)]., Conclusions: CT and SUVmax had low sensitivity but high specificity for predicting MLN metastases in solid NSCLCs 10.1-30.0 mm. Clinical Stage IA NSCLCs ≤ 30 mm should be based on CT maximum tumor diameter and MLN maximum short-axis diameter ≤ 20 mm., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: The role of specific immune cell types within the tumor immune microenvironment in non-small cell lung cancer survival is unclear. The potential of these immune cells to become predictive biomarkers of prognosis, and to define subpopulations who will benefit of additional treatment is urgently needed., Methods: Stage I to IIIA non-small cell lung cancer patients who underwent surgical resection were queried from the Cancer Genome Atlas; RNAseq data as well as clinical information was extracted. Sample-specific scores for different immune cells were computed via xCell. The association between each cell type and survival was assessed with Cox regression, both unadjusted and adjusted for sex, stage, smoking status, and tumor purity. Models were stratified by lung adenocarcinoma and lung squamous cell carcinoma., Results: There were 383 lung adenocarcinoma and 328 lung squamous cell carcinoma samples, and 161 (42%) and 124 (38%) deaths respectively. There was no association between any immune cell infiltrations and survival in the combined unadjusted Cox regression model. After adjustment, the presence of CD8+ cytotoxic T cells (adjusted hazard ratio [HRajd]: 0.84; 95% confidence interval [CI]: 0.71-0.99; P=0.03), CD4+ helper T cells (HRajd: 0.79; 95% CI: 0.66-0.95; P=0.01) and CD20+ B cells (HRajd: 0.80; 95% CI: 0.66-0.97; P=0.02) were significant predictors of decreased risk of death., Conclusions: This study shows that the adjustment for clinical characteristics is key when evaluating tumor immune infiltration and its association with cancer outcomes. Adjustment for confounding factors modified the prognostic significance of specific immune cell populations in early-stage surgically resected NSCLC cases; clinical attributes may have high relevance on immune infiltration composition., Competing Interests: R.V. has received consulting honorarium from Onconova Pharmaceuticals. The remaining authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Sociodemographic disparities in lung cancer prevalence, treatment options offered, and outcomes have been well documented. In stage I non-small cell lung cancer (NSCLC), the standard of care is surgical resection. This study explores disparities in surgical recommendations in stage I NSCLC, when surgery is considered curative., Materials and Methods: Patients diagnosed with primary stage I NSCLC from 2007 to 2016 were identified from the Surveillance, Epidemiology, and End Results database (N=56,534). Associations between sociodemographic variables and surgical recommendation were assessed using multivariable logistic regression models. Survival impact was investigated using Cox-proportional hazards regression and propensity matching techniques., Results: Of the 76.9% patients recommended surgery, 95% underwent surgery. Recommended surgery was inversely associated with increasing age (P<0.01), non-Hispanic Black race (adjusted odds ratio [ORadj] 0.64, 95% confidence interval [CI]: 0.59-0.70), Hispanic ethnicity (ORadj 0.75, 95% CI: 0.67-0.84), nonprivate/Medicare insurance (Medicaid: ORadj 0.55, 95% CI: 0.51-0.60; insured with unknown plan: ORadj 0.74, 95% CI: 0.69-0.79; uninsured: ORadj 0.45, 95% CI: 0.36-0.55), and single status (ORadj 0.66, 95% CI: 0.63-0.70). Patients who were not recommended surgery were at increased risk of death compared with those who were recommended., Conclusion: In a cohort of NSCLC patients, nonclinical factors identified a subgroup of patients who were less likely to be recommended surgery.

Background: Self-reported smoking behavior is widely used in identifying the eligibility for lung cancer screening (LCS). In clinical trials, self-reported smoking status was shown to be a reliable measure, while its effectiveness outside of trial settings remains to be clarified. We aimed to verify self-reported smoking status with serum cotinine levels among LCS-eligible adults from the National Health and Nutrition Examination Survey (NHANES)., Methods: From the combined 1999-2018 NHANES data, we selected adults (aged ≥18 years) with complete data on serum cotinine and smoking behavior, and determined their LCS eligibility according to the United States Preventive Services Task Force recommendation. Using established race/ethnicity specific cotinine cutpoints as the gold standard, we verified self-reported current smoking status with five measures: sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and reliability Kappa. We also compared these performance measures in subgroups stratified by sex, race/ethnicity, education, family income to poverty ratio, health insurance, and secondhand smoking exposure (SHS) at home. All analyses took into account the complex survey design., Results: Approximately 9.3% (n = 2335, equivalent to 8.82 million weighted population) of all adults who currently smoke or formerly smoked were eligible for LCS. The prevalence of current smoking was 52.6% and 60.8% based on self-report and cotinine, respectively. The Se and Sp were 86.4% (95%CI: 83.9%-88.9%) and 99.7% (95%CI: 99.4%-100%), respectively; PPV and NPV were 99.8% (95%CI: 99.6%-100%) and 82.6% (95%CI: 79.4%-85.7%), respectively; and Kappa was 0.83 (95%CI: 0.80-0.86). The reliability Kappa was higher among females than males (0.87 (95%CI: 0.82-0.93)) vs 0.80 (95%CI: 0.77-0.84), the lowest among non-Hispanic white (0.82 (95%CI: 0.78-0.86)), and higher among those with SHS (0.72 (95%CI: 0.63-0.80) vs (0.68 (95%CI: 0.61-0.76))., Conclusion: Self-reported smoking status is reasonably reliable among adults with high risk for developing lung cancer in the general population., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) has been a reimbursable preventive service covered by Medicare since 2015. Geographic disparities in the access to LDCT providers may contribute to the low uptake of LCS. We evaluated LDCT service availability for older adults in the United States (US) based on Medicare claims data and explored its ecological correlation with smoking prevalence. Materials and Methods: We identified providers who provided at least 11 LDCT services in 2016 using the Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File. We constructed a 30-mile Euclidian distance buffer around each provider's location to estimate individual LDCT coverage areas. We then mapped the county-level density of LDCT providers and the county-level prevalence of current daily cigarette smoking in a bivariate choropleth map. Results: Approximately 1/5 of census tracts had no LDCT providers within 30 miles and 46% of counties had no LDCT services. At the county level, the median LDCT density was 0.5 (interquartile range (IQR): 0-5.3) providers per 1000 Medicare fee-for-service beneficiaries, and cigarette smoking prevalence was 17.5% (IQR: 15.2-19.8%). High LDCT service availability was most concentrated in the northeast US, revealing a misalignment with areas of high current smoking prevalence, which tended to be in the central and southern US. Conclusions: Our maps highlight areas in need for enhanced workforce and capacity building aimed at reducing disparities in the access and utilization of LDCT services among older adults in the US.

Background: Robotic-assisted surgery (RAS) is a novel surgical approach increasingly used for patients with non-small cell lung cancer (NSCLC). However, data comparing the effectiveness and costs of RAS vs open thoracotomy and video-assisted thoracoscopic surgery (VATS) for NSCLC are limited., Methods: Patients > 65 years old with stage I to IIIA NSCLC treated with RAS, VATS, or open thoracotomy were identified from the Surveillance, Epidemiology, and End Results-Medicare database and matched according to age, sex, stage, and extent of resection. Propensity score methods were used to compare adjusted rates of postoperative complications, adequate lymph node staging, survival, and treatment-related costs., Results: In this matched study cohort of 2,766 patients with resected NSCLC, RAS was associated with lower complication rates (OR, 0.57; 95% CI, 0.42-0.79) compared with open thoracotomy, and similar complication rates (OR, 1.02; 95% CI, 0.76-1.37) compared with VATS. Patients undergoing RAS were as likely to have adequate lymph node sampling as those undergoing open thoracotomy (OR, 1.28; 95% CI, 0.94-1.74) or VATS (OR, 0.88; 95% CI, 0.66-1.18). There was no significant difference in overall survival after RAS vs open thoracotomy (hazard ratio, 0.81; 95% CI, 0.63-1.04) or VATS (hazard ratio, 0.91; 95% CI, 0.70-1.18). Costs were similar for RAS ($54,702) vs open thoracotomy ($57,104; P = .08), and higher compared with VATS ($48,729; P = .02)., Conclusions: RAS led to improved operative outcomes compared with open thoracotomy but may not offer an advantage over VATS. The comparative effectiveness of RAS should be further evaluated prior to widespread adoption., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Lung cancer screening (LCS) is an important secondary prevention measure to reduce lung cancer mortality. The goal of this study was to assess state-level variations in LCS among the US elderly during the first 3 years since Medicare began its LCS reimbursement policy in 2015., Methods: This ecological study examined the relations between LCS utilization density, defined as the number of low-dose CT (LDCT) or shared decision-making and counseling (SDMC) services per 1,000 Medicare fee-for-service (FFS) beneficiaries derived from the Medicare Provider Utilization and Payment Data: Physician and Other Supplier public use file, and state-level factors from several publicly available data sources. The study included Kruskal-Wallis tests and a cluster analysis., Results: In 2017, the median utilization density per 1,000 Medicare FFS beneficiaries was 3.32 for LDCT and 0.46 for SDMC, which was 24 and 13 times the 2015 level, respectively. From 2015 to 2017, the total number of unique providers billed for LCS increased from 222 to 3,444 for LDCT imaging and from 20 to 523 for SDMC. Higher utilizations for both LDCT and SDMC services tended to concentrate in the northeastern and upper Midwest states than in the southwest states. The cluster of states with high utilization density did not include those states with the most lung cancer mortality and/or smoking prevalence., Conclusions: A steady increase was noted in LCS utilization since Medicare began its reimbursement policy. The utilization and its growth varied across the United States and differed between LDCT imaging and SDMC, indicating large growth potentials for LCS and for states with high lung cancer mortality and smoking prevalence., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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

Background: Surgery is the preferred treatment for stage I non-small cell lung cancer (NSCLC), with radiation reserved for those not receiving surgery. Previous studies have shown lower rates of surgery among Blacks with stage I NSCLC than among Whites., Methods: Black and White men ages ≥65 years with stage I NSCLC diagnosed between 2001 and 2009 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and Veterans Affairs (VA) cancer registry. Logistic regression and Cox proportional hazards models were used to examine associations between race, treatment, and survival., Results: Among the patients in the VA ( n = 7,895) and SEER ( n = 8,744), the proportion of Blacks was 13% and 7%, respectively. Overall, 16.2% of SEER patients (15.4% of Whites, 26.0% of Blacks) and 24.5% of VA patients received no treatment (23.4% of Whites, 31.4% of Blacks). In both cohorts, Blacks were less likely to receive any treatment compared with Whites [OR adj = 0.57; 95% confidence interval (CI), 0.47-0.69 for SEER-Medicare; OR adj = 0.68; 95% CI, 0.58-0.79 for VA]. Among treated patients, Blacks were less likely than Whites to receive surgery only (OR adj = 0.57; 95% CI, 0.47-0.70 for SEER-Medicare; OR adj = 0.73; 95% CI, 0.62-0.86 for VA), but more likely to receive chemotherapy only and radiation only. There were no racial differences in survival., Conclusions: Among VA and SEER-Medicare patients, Blacks were less likely to get surgical treatment. Blacks and Whites had similar survival outcomes when accounting for treatment., Impact: This supports the hypothesis that equal treatment correlates with equal outcomes and emphasizes the need to understand multilevel predictors of lung cancer treatment disparities., (©2019 American Association for Cancer Research.)

Background: An appropriate treatment of older lung cancer patients has become an important issue. The aim of this study is to evaluate the short and long-term surgical outcomes in lung cancer patients using 70 years as a cut-point, and to identify prognostic factors of cancer-specific mortality in patients older than 70 years., Methods: Medical records of non-small cell lung cancer (NSCLC) patients who underwent pulmonary resection at Chiang Mai University Hospital from January 2002 through December 2016 were retrospectively reviewed. Patients were divided into age less than 70 years (control group) and 70 years or more (study group). Primary outcomes were major post-operative complications and in-hospital death (POM); secondary outcome was long-term survival. Multivariable regression analysis was used., Results: This study included 583 patients, 167 for study group, and 416 for control group. There were no differences in POM, both at univariable and multivariable analyses, however, for long-term cancer-specific mortality, the study group was more likely to die (HR adj  = 1.40, 95%CI = 1.03-1.89). Adverse prognostic factors for long-term mortality in study group were having universal coverage scheme (HR adj  = 1.70, 95%CI = 1.03-2.79), the presence of intratumoral lymphatic invasion (HR adj  = 2.83, 95%CI = 1.28-6.29), perineural invasion (HR adj  = 2.80, 95%CI = 1.13-6.94), underwent lymph node sampling (HR adj  = 2.23, 95%CI = 1.16-4.30) and higher stage of disease (HR adj  = 2.02, 95%CI = 1.06-3.85 for stage III, HR adj  = 3.40, 95%CI = 1.29-8.94 for stage IV)., Conclusions: In-hospital mortality and composite post-operative complications are acceptable in pulmonary resection for NSCLC patients older than 70 years. However, these patients had shorter long-term survival, especially who have some adverse prognostic factors. Further studies with larger sample size are warranted., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Background: Patients who have undergone curative surgery for stage I lung cancer require continued surveillance owing to the risk of a second primary lung cancer developing. Early diagnosis allows for prompt intervention. However, as in primary cancers, the role of wedge vs lobar resections remains controversial., Methods: The Surveillance Epidemiology and End Results database was examined from 2004 to 2012 and all pathologically proven stage I lung cancer patients who underwent cancer-directed surgery were selected. Cases in which a second primary lung cancer developed 6 or more months after diagnosis of the first cancer were analyzed for survival after surgical treatment., Results: Second primary lung cancer was identified in 625 patients, of whom 331 (53%) were diagnosed with stage I disease; 43.8% of patients underwent surgery alone, 30.9% received radiation alone, and 21.0% received neither surgery nor radiation. Of the patients who underwent surgery, 57.7% received wedge resection and 36.5% received a lobectomy. Surgical intervention was a positive predictor of survival-both wedge resection and lobectomy exhibited improved outcomes vs no surgery-but there was no statistically significant difference between the two surgical modalities., Conclusions: Wedge and lobar resections demonstrate similar survival for second primary lung cancers., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer, and early detection is associated with better survival. Mesothelin, fibulin-3 and osteopontin have been suggested as screening biomarkers. The study conducted a meta-analysis of the mean differences of mesothelin, osteopontin and fibulin-3 in blood and pleural samples. PubMed searches were conducted for studies that measured levels of mesothelin, osteopontin and fibulin-3 in participants with MPM compared with malignancy, benign lung disease or healthy participants. Thirty-two studies with mesothelin levels, 12 studies with osteopontin levels and 9 studies with fibulin-3 levels were included in the meta-analysis. Statistically significant mean differences were seen between MPM patients and all other comparison groups for mesothelin blood and pleural levels. Statistically significant differences in blood osteopontin levels were seen between participants with benign lung disease and healthy participants compared with participants with MPM, but not when comparing participants with cancer with MPM participants. There were not enough studies that reported osteopontin levels in pleural fluid to complete a meta-analysis. Statistically significant differences were seen in both blood and pleural levels of fibulin-3 in MPM patients compared with all other groups. On the basis of these results, mesothelin and fibulin-3 levels appear to be significantly lower in all control groups compared with those with MPM, making them good candidates for screening biomarkers. Osteopontin may be a useful biomarker for screening healthy individuals or those with benign lung disease but would not be useful for screening patients with malignancies., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Rationale: Characteristics and outcomes of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) in the United States remain understudied. Objectives: To determine the tumor characteristics and survival of patients with IPF with non-small cell lung cancer (NSCLC) using U.S. population-based data. Methods: We selected Medicare beneficiaries from the Surveillance, Epidemiology, and End Results registry with histologically confirmed NSCLC diagnosed between 2007 and 2011. IPF was identified using two validated claims-based algorithms. We compared tumor characteristics and used logistic and Cox regression to compare rates of stage-appropriate therapy and of overall and lung cancer-specific survival in those with IPF and without IPF. Results: A total of 54,453 patients with NSCLC were included. Those with IPF were more likely to be diagnosed at an earlier stage ( P  < 0.01) and to have squamous histology (46% vs. 35%; P  < 0.01) and lower-lobe tumors (38% vs. 28%; P  < 0.01) than those without IPF. Patients with IPF and stages I-II disease had odds of receiving stage-appropriate therapy similar to patients without IPF who had stages I-II disease (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.89-1.43); however, those with advanced disease were less likely to be treated (OR, 0.82; 95% CI, 0.68-0.99). Overall and lung cancer-specific survival were worse in patients with IPF (respectively, hazard ratio [HR], 1.35; 95% CI, 1.26-1.45; and HR, 1.21; 95% CI, 1.10-1.32). Conclusions: NSCLC has a unique presentation in patients with IPF and is associated with poorer prognosis. Further research is needed to identify optimal treatment strategies in this population.

Malignant pleural mesothelioma (MPM) is a rare disease with a very poor prognosis. Previous studies have indicated that women experience longer survival compared with men. We analyzed 16 267 eligible patients (21.3% females) in the National Cancer Database to evaluate which clinical factors are independently predictive of longer survival. After adjusting for all covariates, survival was significantly better in females compared with males [HRadj: 0.81, 95% confidence interval (CI): 0.77-0.85]. Other factors significantly associated with better survival were younger age at diagnosis, higher income, lower comorbidity score, epithelial histology, earlier stage and receipt of surgical or medical treatment. After propensity matching, survival was significantly better for females compared with males [hazard ratio (HR): 0.86, 95% CI: 0.80-0.94]. After propensity matching within the epithelial group, survival remained significantly better for females compared with males (HR: 0.85, 95% CI: 0.74-0.97). This study adds information to the known significant gender survival difference in MPM by disentangling the effect of gender from the effect of age and histology, two known independent factors affecting survival. Circulating estrogen, present in young but not older women, and higher expression of the estrogen receptor beta in epithelial mesothelioma have been suggested to play a role in gender survival differences. These findings may lead to exploring new therapeutic options, such as targeting estrogen receptor beta, and considering hormonal therapy including estrogens for patients with otherwise limited prognosis., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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

Objective: Although the incidence of lung cancer has decreased over the past decades, disparities in survival and treatment modalities have been observed for black and white patients with early-stage non-small cell lung cancer, despite the fact that surgical resection has been established as the standard of care. Possible contributors to these disparities are stage at diagnosis, comorbidities, socioeconomic factors, and patient preference. This study examines racial disparities in treatment, adjusting for clinicodemographic factors., Methods: The Surveillance, Epidemiology, and End Results-Medicare dataset was queried to identify patients diagnosed with primary stage I non-small cell lung cancer between 1992 and 2009. Multivariable logistic regressions were performed to assess the association between race and treatment modalities within 1 year of diagnosis, adjusted for clinical and demographic factors. Adjusted Cox proportional hazards models were performed to evaluate disparities in survival, accounting for mode of treatment., Results: We identified 22,724 patients; 21,230 (93.4%) white and 1494 (6.6%) black. Black patients were less likely to receive treatment (odds ratio [OR] adj , 0.62; 95% confidence interval [CI], 0.53-0.73) and less likely to receive surgery only when treated (OR adj , 0.70, 95% CI, 0.61-0.79). Although univariate survival for black patients was worse, when accounting for treatment mode, there was no difference in survival (hazard ratio adj , 0.97; 95% CI, 0.90-1.04 for all patients, hazard ratio adj , 0.98; 95% CI: 0.90-1.06 for treated patients)., Conclusions: Treatment disparities persist, even when adjusting for clinical and demographic factors. However, when black patients receive similar treatment, survival is comparable with white patients., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Sublobar resection is often used as an alternative surgical approach in lung cancer patients who are unlikely to tolerate a full lobe resection. This study aims to assess outcomes of video-assisted thoracoscopic surgeries (VATS) sublobar resection as a surgical technique., Materials and Methods: The SEER-Medicare database was queried to identify patients with primary lung cancer who had VATS or open sublobar resection. Baseline clinical differences between VATS and open patients were adjusted for in logistic regression and by propensity score matching to investigate surgical outcomes., Results: Patients undergoing VATS had a greater number of comorbidities (adjusted odds ratio [ORadj], 0.90; 95% confidence interval [CI], 0.85-0.96) and were less likely to have later stage cancer (ORadj, 0.80; 95% CI, 0.67-0.95), squamous compared with adenocarcinoma (ORadj, 0.82; 95% CI, 0.68-0.99), large (>30 mm) tumor size (ORadj, 0.56; 95% CI, 0.0.41-0.75). VATS patients were less likely to have nodes removed for examination during surgery (ORadj, 0.76; 95% CI, 0.64-0.90). After propensity matching (n=2148), patients who underwent VATS were less likely to experience in-hospital complications, blood transfusions, and a prolonged length of hospital stay than those who had open surgery. There was no statistically significant difference in in-hospital or long-term mortality between patients with VATS and open surgery., Conclusion: In the most compromised lung cancer patients, VATS sublobar resection might be the best option.

Background: Few studies have focused on quality of life (QoL) after treatment of malignant pleural mesothelioma (MPM). There are still questions as to which surgical procedure, extrapleural pneumonectomy (EPP) or pleurectomy decortication (P/D) is most effective and results in better survival outcomes, involves fewer complications, and results in better QoL. Here we performed a literature review on MPM patients to assess and compare QoL changes after P/D and EPP., Methods: Research articles concerning QoL after mesothelioma surgery were identified through May 2018 in Medline. For inclusion, studies were 1) cohort or randomized controlled trials (RCT) design, 2) included standardized QoL instruments, 3) reported QoL measurement after surgery, 4) described the type of surgery performed (EPP or P/D), 5) were written in English. Measures of lung function (FEV1, FVC) and measures from the EORTC-C30 were compared 6 months following surgery with preoperative values., Results: QoL data was extracted from 17 articles (14 datasets), encompassing 659 patients (102 EPP, 432 P/D); the available evidence was of low quality. While two studies directly compared QoL between the two surgical procedures, additional data was available from one arm of two RCTs, as the RCTs were not comparing EPP and P/D. The remaining data was reported from observational studies. While QoL was still compromised 6 months following surgery, from the limited and low quality data available it would appear that P/D patients had better QoL than EPP patients across all measures. Physical function, social function and global health were better at follow-up for P/D than for EPP, while other indicators such as pain and cough were similar. Forced Expiratory Volume (FEV1) and Forced Vital Capacity (FVC) were reported in one study only, and were higher at follow-up for P/D compared to EPP., Conclusions: Although the existing evidence is limited and of low quality, it suggests that P/D patients have better QoL than EPP patients following surgery. QoL outcomes should be factored into the choice of surgical procedure for MPM patients, and the possible effects on lung function and QoL should be discussed with patients when presenting surgical treatment options.

On March 28- 29, 2017, the National Cancer Institute (NCI) Thoracic Malignacy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation convened the NCI-International Association for the Study of Lung Cancer- Mesothelioma Applied Research Foundation Mesothelioma Clinical Trials Planning Meeting in Bethesda, Maryland. The goal of the meeting was to bring together lead academicians, clinicians, scientists, and the U.S. Food and Drug Administration to focus on the development of clinical trials for patients in whom malignant pleural mesothelioma has been diagnosed. In light of the discovery of new cancer targets affecting the clinical development of novel agents and immunotherapies in malignant mesothelioma, the objective of this meeting was to assemble a consensus on at least two or three practice-changing multimodality clinical trials to be conducted through NCI's National Clinical Trials Network., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Background: There are no published reports on predictors of oxygen (O 2 ) use after lung cancer surgery. The prospect of O 2 use after lung cancer surgery may affect a patient's therapy choice., Methods: The Surveillance, Epidemiology, and End Results (SEER)-Medicare data set was queried to identify patients diagnosed with primary lung cancer (stage I/II) who underwent surgical resection from 1994 to 2010. Patients with a second resection within 6 months of their first and those with preoperative O 2 use were excluded. Multivariable logistic regression was performed to evaluate the odds ratios and 95% confidence intervals of O 2 use (defined as being billed for home O 2 ) after discharge for lung cancer surgery., Results: Of 21,245 eligible patients from 1994 to 2010, 3,255 (15.3%) were billed for O 2 use in the first month of discharge. Of these, 13.7% (447 of 3,255) stopped using within 1 month, and 1.47% died. By 6 months, an additional 6.7% died, and 46.27% (1,384 of 2,991) were still alive and using O 2. Discharge on O 2 was associated with higher odds of death within 6 months (odds ratio, 1.35; 95% confidence interval, 1.17 to 1.55). The significant, independent risk factors for O 2 use at discharge were procedure, sex, race, histology, pulmonary comorbidities, obesity, length of stay, pulmonary complications, and discharge mode., Conclusions: Home O 2 use after lung cancer surgery comprises a sizable portion of this population and is correlated with death in the first 6 months. Various predictors significantly increased the risk of O 2 use at discharge. However, 49.3% of those originally discharged on O 2 were alive and off O 2 at 6 months., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: To maximize the benefits of computed tomographic screening for lung cancer, optimal treatment for small, early lung cancers is needed. Limiting the extent of surgery spares lung tissue, preserves pulmonary function, and decreases operative time, complications, and morbidities. It also increases the likelihood of resecting future new primary lung cancers. The goal is to assess alternative treatments in a timely manner., Methods: The focus sessions with patients and physicians separately highlighted the need to consider their perceptions. Literature reviews and analyses of treatment results using large databases were performed to formulate critical questions about long-term treatment outcomes, recurrence, and quality of life of alternative treatments. Based on these analyses, the investigators developed a prospective multi-institutional cohort study, the Initiative for Early Lung Cancer Research for Treatment, to compare treatments for stage I NSCLC. HIPAA compliant institutional review board approval was obtained and we performed a feasibility study of the first 206 surgical patients., Results: Lobectomy was performed in 89 (43.2%) patients, and sublobar resection was performed in 117 (56.7%) patients. Mediastinal lymph node resection was performed in 173 (84.0%) patients, 8 had N1 and 3 N2 lymph node metastases. Patients stated that both the surgeon's opinion (93%) and the patient's own opinion (93%) were extremely important, followed by the patients' view that the chosen procedure would provide the best quality of life (90%)., Conclusions: It was feasible to obtain pre- and postsurgical information from patients and surgeons. We anticipate statistically meaningful results about treatment alternatives in 3 to 5 years., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The effect of insurance type on lung cancer diagnosis, treatment, and survival in Asian patients living in the United States is still under debate. We have analyzed this issue using the Surveillance, Epidemiology, and End Results database. There were 102,733 lung cancer patients age 18-64 years diagnosed between 2007 and 2013. Multilevel regression analysis was performed to identify the association between insurance types, stage at diagnosis, treatment modalities, and overall mortality in Asian and non-Hispanic White (NHW) patients. Clinical characteristics were significantly different between Asian and NHW patients, except for gender. Asian patients were more likely to present with advanced disease than NHW patients (OR adj  = 1.12, 95% CI = 1.06-1.19). Asian patients with non-Medicaid insurance underwent lobectomy more than NHW patients with Medicaid or uninsured; were more likely to undergo mediastinal lymph node evaluation (MLNE) (OR adj  = 1.98, 95% CI = 1.72-2.28) and cancer-directed surgery and/or radiation therapy (OR adj  = 1.41, 95% CI = 1.20-1.65). Asian patients with non-Medicaid insurance had the best overall survival. Uninsured or Medicaid-covered Asian patients were more likely to be diagnosed with advanced disease, less likely to undergo MLNE and cancer-directed treatments, and had shorter overall survival than their NHW counterpart., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Lung cancer screening with low-dose computed tomography has been shown to significantly reduce lung cancer-related mortality in high-risk patients. However, patients diagnosed with lung cancer are typically older and often have multiple age- and smoking-related comorbidities. As a result, cancer screening in older adults remains a complex decision, requiring careful consideration of patients' risk characteristics and life expectancy to ensure that the benefits outweigh the risks of screening. In this review, we evaluate the evidence regarding lung cancer screening, with a focus on older patients., Methods: PubMed was searched to identify relevant studies evaluating the clinical outcomes of lung cancer screening. The key words used in our search included non-small cell lung cancer (NSCLC), screening, older, comorbidities, computed tomography, and survival. While we primarily looked for articles specific to older patients, we also focused on subgroup analysis in older patients in larger studies. Finally, we reviewed all relevant guidelines regarding lung cancer screening., Findings: Guidelines recommend that lung cancer screening be considered in adults aged 55 to 80 years who are at high risk based on smoking history (ie, 30-pack-year smoking history; having smoked within the past 15 years). Patients who fit these criteria have been shown to have a 20% reduction in lung cancer-related mortality with the use of low-dose computed tomography versus chest radiography. High rates of false-positive results and potential overdiagnoses were also observed. Therefore, screening is generally not recommended in adults with severe comorbidities or short life expectancy, who may experience limited benefit and higher risks with screening. However, several studies have shown a benefit with continued lung cancer screening with appropriate selection of older individuals at the highest risk and with the lowest comorbidities., Implications: Older patients experience the highest risk for lung cancer incidence and mortality, and stand to be the most likely to benefit from lung cancer screening. However, careful consideration must be given to higher rates of false-positives and overdiagnosis in this population, as well as tolerability of surgery and competing risks for death from other causes. The appropriate selection of older individuals for lung cancer screening can be greatly optimized by using validated risk-based targeting., (Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.)

Background: Studies reporting the benefits of video-assisted thoracoscopic surgery (VATS) lung cancer resection over thoracotomy have been subject to selection bias. We evaluated patient and hospital characteristics associated with type of surgery and the independent effect of VATS on outcomes., Methods: The Statewide Planning and Research Cooperative System of New York State database was queried to identify all lung cancer patients undergoing lobectomy or sublobar resection between 2007 and 2012. Multivariable logistic regression was performed to identify patient (age, sex, race, comorbidities, year, and insurance) and hospital (urban, teaching, and total lung surgery volume) cofactors associated with surgical technique and propensity scores were used to evaluate whether technique was independently associated with complications or in-hospital mortality., Results: There were 5,505 lobectomy and 4,282 sublobar resection patients, with 2,318 (42%) and 2,416 (56%) undergoing VATS, respectively. For lobectomy, VATS was associated with being female, lower comorbidity index, private insurance, older age, surgery in recent year, nonteaching hospital, and higher annual lung surgery volume. For sublobar resection, VATS was associated with black race, lower comorbidity index, Medicaid or other insurance, surgery in recent year, rural hospital, and higher annual lung surgery volume. Complication rate was significantly lower for VATS lobectomy and not sublobar resection, whereas in-hospital mortality was lower for VATS in both resection groups., Conclusions: Numerous patient- and hospital-related variables that affect morbidity and mortality also affect whether a patient undergoes VATS or open lung resection. Studies evaluating VATS must account more accurately for selection bias and adjust for these confounders., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Mediastinal lymph node evaluation (MLNE) is considered to be the standard of care in curative lung cancer surgery although it is not always performed. This study identifies factors associated with patients not being evaluated (non-MLNE) in cases of resectable non-small cell lung cancer., Methods: A retrospective observational study using the Surveillance, Epidemiology, and End Results Program database was conducted. Adult patients diagnosed with non-small cell lung cancer stage I to IIIA (2004 to 2013) were included. Multilevel logistic regression analysis was performed to identify factors that were associated with non-MLNE., Results: There were 86,721 patients included in this study: 73,034 (84.2%) with MLNE and 13,687 (15.8%) without. The use of MLNE gradually increased from 82.7% in 2004 to 85.8% in 2013. In multivariable analysis, factors associated with non-MLNE included the following: age more than 75 years (adjusted odds ratio [OR adj ] 1.20, 95% confidence interval [CI]: 1.13 to 1.27); black (OR adj 1.11, 95% CI: 1.32 to 1.20); Native American/Alaskan (OR adj 1.63, 95% CI: 1.15 to 2.31); uninsured (OR adj 1.28, 95% CI: 1.05 to 1.56); residing in a low-income county (OR adj 1.12, 95% CI: 1.04 to 1.21); lesion at the middle lobe (OR adj 1.42, 95% CI: 1.29 to 1.56); lower lobe (OR adj 1.06, 95% CI: 1.01 to 1.11) or main bronchus (OR adj 2.38, 95% CI: 1.93 to 2.94); stage IA (OR adj 1.24, 95% CI: 1.17 to 1.32); sublobar resection (OR adj 11.08, 95% CI: 11.30 to 12.33); and preoperative treatment (OR adj 1.21, 95% CI: 1.08 to 1.36). Non-MLNE was less likely to occur in patients with adenocarcinoma (OR adj 0.88, 95% CI: 0.83 to 0.92) and more likely in other cell types (OR adj 1.23, 95% CI: 1.15 to 1.32), compared with squamous cell carcinoma., Conclusions: Patient demographics and socioeconomic status are associated with the decision to perform MLNE. Thoracic surgeons should access these factors and perform MLNE to accurately determine tumor stage and improve survival., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

This review summarizes the literature on QoL in early stage lung cancer patients who underwent surgery. PubMed and PsycINFO were searched. Twelve articles from 10 distinct studies were identified for a total of 992 patients. Five QoL measures were used. One study reported only on pre-surgical QoL, six only on post-surgical QoL and three studies reported on both pre- and post-surgical QoL. Timing for the administration of post-surgical QoL surveys varied. The literature on QoL in Stage I non-small-cell lung cancer patients is very sparse. Additional research is needed to explore the impact of different surgical approaches on QoL.