Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses.

To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single-cell analysis of the tumor, non-involved lung, and blood cells, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments. Moreover, we identified changes in tumor-infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor T cell immunity. Paired single-cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies. VIDEO ABSTRACT.

A conserved dendritic-cell regulatory program limits antitumour immunity.

Checkpoint blockade therapies have improved cancer treatment, but such immunotherapy regimens fail in a large subset of patients. Conventional type 1 dendritic cells (DC1s) control the response to checkpoint blockade in preclinical models and are associated with better overall survival in patients with cancer, reflecting the specialized ability of these cells to prime the responses of CD8+ T cells1-3. Paradoxically, however, DC1s can be found in tumours that resist checkpoint blockade, suggesting that the functions of these cells may be altered in some lesions. Here, using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, we identify a cluster of dendritic cells (DCs) that we name 'mature DCs enriched in immunoregulatory molecules' (mregDCs), owing to their coexpression of immunoregulatory genes (Cd274, Pdcd1lg2 and Cd200) and maturation genes (Cd40, Ccr7 and Il12b). We find that the mregDC program is expressed by canonical DC1s and DC2s upon uptake of tumour antigens. We further find that upregulation of the programmed death ligand 1 protein-a key checkpoint molecule-in mregDCs is induced by the receptor tyrosine kinase AXL, while upregulation of interleukin (IL)-12 depends strictly on interferon-γ and is controlled negatively by IL-4 signalling. Blocking IL-4 enhances IL-12 production by tumour-antigen-bearing mregDC1s, expands the pool of tumour-infiltrating effector T cells and reduces tumour burden. We have therefore uncovered a regulatory module associated with tumour-antigen uptake that reduces DC1 functionality in human and mouse cancers.

Author Correction: A conserved dendritic-cell regulatory program limits antitumour immunity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Longitudinal quality of life after sublobar resection and stereotactic body radiation therapy for early-stage non-small cell lung cancer.

BACKGROUND: Many patients with early-stage lung cancer are not candidates for lobectomy because of various factors, with treatment options including sublobar resection or stereotactic body radiation therapy (SBRT). Limited information exists regarding patient-centered outcomes after these treatments. METHODS: Subjects with stage I-IIA non-small cell lung cancer (NSCLC) at high risk for lobectomy who underwent treatment with sublobar resection or SBRT were recruited from five medical centers. Quality of life (QOL) was compared with the Short Form 8 (SF-8) for physical and mental health and Functional Assessment of Cancer Therapy-Lung (FACT-L) surveys at baseline (pretreatment) and 7 days, 30 days, 6 months, and 12 months after treatment. Propensity score methods were used to control for confounders. RESULTS: Of 337 subjects enrolled before treatment, 63% received SBRT. Among patients undergoing resection, 89% underwent minimally invasive video-assisted thoracic surgery or robot-assisted resection. Adjusted analyses showed that SBRT-treated patients had both higher physical health SF-8 scores (difference in differences [DID], 6.42; p = .0008) and FACT-L scores (DID, 2.47; p = .004) at 7 days posttreatment. Mental health SF-8 scores were not different at 7 days (p = .06). There were no significant differences in QOL at other time points, and all QOL scores returned to baseline by 12 months for both groups. CONCLUSIONS: SBRT is associated with better QOL immediately posttreatment compared with sublobar resection. However, both treatment groups reported similar QOL at later time points, with a return to baseline QOL. These findings suggest that sublobar resection and SBRT have a similar impact on the QOL of patients with early-stage lung cancer deemed ineligible for lobectomy.

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

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

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

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

Disparities in clinical and demographic characteristics among Asian/Pacific Islander and Non-Hispanic White newly diagnosed lung cancer patients.

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 (ORadj 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 (ORadj 0.85, 95% CI 0.83-0.86), and unmarried (ORadj 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 (ORadj 1.31, 95% CI 1.27-1.35). API had significantly less squamous cell carcinoma (ORadj 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: ORadj[Other] 1.24, 95% CI 1.09-1.41; ORadj[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.

Modulation of chemoimmunotherapy efficacy in non-small cell lung cancer by sex and histology: a real-world, patient-level analysis.

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 (HRadj: 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 (HRadj: 0.73, 95% CI: 0.58-0.91 vs HRadj: 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.

A Neighborhood Analysis of Time Trends in COVID-19 Infection in NYC.

To understand how observed COVID-19 diagnostic testing disparities across New York City (NYC) have impacted infection rates and COVID-19 spread, we examined neighborhood-level factors associated with, and the spatial distribution of, antibody test and infection rates, and compared changes over time by NYC ZIP code tabulation area (ZCTA). Data were obtained from 2019 American Community Survey 5-year estimates to create an SES index by ZCTA. Other predictors obtained from 2018 census data were the proportions of white residents, Hispanic residents and residents ≥ 65 years old. Multivariable Poisson regressions were performed to assess the rate of change for antibody testing and positivity, and to assess the independent associations with SES, race and age. Results: There was a significant association between the rate of antibody tests and SES quartiles (Q1: ßadj = 0.04, Q2: ßadj = 0.03 and Q3: ßadj = - 0.03, compared to Q4), and the proportion of residents who are white (ßadj = 0.004, p < .0001), Hispanic   (ßadj = 0.001, p < .0001), and ≥ 65 years (ßadj = 0.01, p < .0001). Total number of positive antibody tests was significantly inversely associated with SES quartile (Q1: ßadj = 0.50, Q2: ßadj = 0.48 and Q3: ßadj = 0.29, compared to Q4), and proportion of white residents (ß = - 0.001, p < .0001) and ≥ 65 years (ß = - 0.02, p < .0001), and significantly positively associated with proportion of Hispanic residents (ß = 0.003, p < .0001). There are disparities in antibody testing and positivity, reflecting disproportionate impacts and undercounts of COVID-19 infection across NYC ZCTAs. Future public health response should increase testing in these vulnerable areas to diminish infection spread.

Major modifications to minimize thoracic esophago-gastric leak and eradicate esophageal stricture after Ivor Lewis esophagectomy.

BACKGROUND: The Ivor Lewis esophagectomy (ILE) remains the procedure of choice for localized middle or lower esophageal carcinoma. Nevertheless, anastomotic leak remains a common complication with rates from 3% to 25% and a stricture rate as high as 40%. The frequency of these complications suggests that the procedure itself may have inherent limitations including the use of potentially ischemic tissue for the esophagogastric anastomosis. We introduce a modified technique that reduces operative steps, preserves blood supply, and uses a modified esophagogastric anastomosis. METHODS: All consecutive patients undergoing ILE with the described modified technique were identified. An esophagram was performed on postoperative day six or seven. To ensure that all cases were identified, anastomotic leaks were defined as any radiographic evidence of contrast extravasation. RESULTS: A total of 110 patients underwent the modified esophagectomy with 2 anastomotic leaks (1.82%) and zero strictures. There was 1 late death but no early deaths (<30 or 90 days) or early re-admissions (<30 days). The average number of risk factors was 2.12, and 98 patients (90%) had at least 1 risk factor in their medical history. CONCLUSIONS: The modifications proposed simplify procedural steps, limit unnecessary dissection and introduce a technique that ends the practice of connecting ischemic tissue. We believe this technique contributes to surgical durability and reduces the rate of postoperative leak and eliminates stricture.

Lifestyle behaviors and intervention preferences of early-stage lung cancer survivors and their family caregivers.

PURPOSE: Lung cancer (LC) is a highly prevalent disease with more survivors diagnosed and treated at earlier stages. There is a need to understand psychological and lifestyle behavior needs to design interventions for this population. Furthermore, understanding the needs and role of family caregivers, especially given the risks associated with second-hand smoke, is needed. METHODS: Thirty-one early-stage (stages I or IIA) LC survivors of (52% men) and 22 (50% women) caregivers (N = 53 total) completed surveys after surgery (baseline) and at 3- and 6-month follow-ups. Participants reported on psychological functioning, smoking, and physical activity (PA) as well as intervention preferences. RESULTS: Survivors reported low levels of psychological distress and 3% were current smokers during the study. Approximately 79% were sedentary and not meeting national PA guidelines. Caregivers also reported minimal psychological distress and were sedentary (62% not meeting guidelines), but a larger proportion continued to smoke following the survivor's cancer diagnosis (14%). Both survivors and caregivers expressed interest in home-based PA interventions but differed regarding preferred format for delivery. Most (64%) caregivers preferred a dyadic format, where survivors and caregivers participate in the intervention together. However, most survivors preferred an individual or group format (57%) for intervention delivery. CONCLUSION: Both LC survivors and family caregivers could benefit from PA interventions, and flexible, dyadic interventions could additionally support smoking cessation for family caregivers.

A risk index for COVID-19 severity is associated with COVID-19 mortality in New York City.

BACKGROUND: New York City (NYC) was the epicenter of the COVID-19 pandemic, and is home to underserved populations with higher prevalence of chronic conditions that put them in danger of more serious infection. Little is known about how the presence of chronic risk factors correlates with mortality at the population level. Here we determine the relationship between these factors and COVD-19 mortality in NYC. METHODS: A cross-sectional study of mortality data obtained from the NYC Coronavirus data repository (03/02/2020-07/06/2020) and the prevalence of neighborhood-level risk factors for COVID-19 severity was performed. A risk index was created based on the CDC criteria for risk of severe illness and complications from COVID-19, and stepwise linear regression was implemented to predict the COVID-19 mortality rate across NYC zip code tabulation areas (ZCTAs) utilizing the risk index, median age, socioeconomic status index, and the racial and Hispanic composition at the ZCTA-level as predictors. RESULTS: The COVID-19 death rate per 100,000 persons significantly decreased with the increasing proportion of white residents (ßadj = - 0.91, SE = 0.31, p = 0.0037), while the increasing proportion of Hispanic residents (ßadj = 0.90, SE = 0.38, p = 0.0200), median age (ßadj = 3.45, SE = 1.74, p = 0.0489), and COVID-19 severity risk index (ßadj = 5.84, SE = 0.82, p <  0.001) were statistically significantly positively associated with death rates. CONCLUSIONS: Disparities in COVID-19 mortality exist across NYC and these vulnerable areas require increased attention, including repeated and widespread testing, to minimize the threat of serious illness and mortality.

Analyzing disparities in COVID-19 testing trends according to risk for COVID-19 severity across New York City.

BACKGROUND: Given the interplay between race and comorbidities on COVID-19 morbidity and mortality, it is vital that testing be performed in areas of greatest need, where more severe cases are expected. The goal of this analysis is to evaluate COVID-19 testing data in NYC relative to risk factors for COVID-19 disease severity and demographic characteristics of NYC neighborhoods. METHODS: COVID-19 testing and the racial/ethnic composition of NYC Zip Code Tabulation Areas (ZCTA) were obtained from the NYC Coronavirus data repository and the American Community Survey, respectively. The prevalence of neighborhood-level risk factors for COVID-19 severity according to the Centers for Disease Control and Prevention criteria for risk of severe illness and complications from COVID-19 were used to create a ZCTA-level risk index. Poisson regressions were performed to study the ratio of total tests relative to the total ZCTA population and the proportion of positive tests relative to the total tests performed over time. RESULTS: From March 2nd-April 6th, the total tests/population (%) was positively associated with the proportion of white residents (IRRadj: 1.0003, 95% CI: 1.0003-1.0004) and the COVID risk index (IRRadj: 1.038, 95% CI: 1.029-1.046). The risk index (IRRadj: 1.017, 95% CI: 0.939-1.101) was not associated with total tests performed from April 6th-May 12th, and inversely associated from May 12th-July 6th (IRRadj: 0.862, 95% CI: 0.814-0.913). From March 2nd-April 6th the COVID risk index was not statistically associated (IRRadj: 1.010, 95% CI: 0.987-1.034) with positive tests/total tests. From April 6th-May 12th, the COVID risk index was positively associated (IRRadj: 1.031, 95% CI: 1.002-1.060), while from May 12th-July 6th, the risk index was inversely associated (IRRadj: 1.135, 95% CI: 1.042-1.237) with positivity. CONCLUSIONS: Testing in NYC has suffered from the lack of availability in high-risk populations, and was initially limited as a diagnostic tool for those with severe symptoms, which were mostly concentrated in areas where vulnerable residents live. Subsequent time periods of testing were not targeted in areas according to COVID-19 disease risk, as these areas still experience more positive tests.

The Association of Cerebral Desaturation During One-Lung Ventilation and Postoperative Recovery: A Prospective Observational Cohort Study.

OBJECTIVES: This study was designed to investigate whether cerebral oxygen desaturations during thoracic surgery are predictive of patients' quality of recovery. As a secondary aim, the authors investigated the relationship among cerebral desaturations and postoperative delirium and hospital length of stay. DESIGN: This study was a prospective observational cohort study. SETTING: A single tertiary-care medical center from September 2012 through March 2014. PATIENTS: Adult patients scheduled for elective pulmonary surgery requiring one-lung ventilation. INTERVENTIONS: All patients were monitored with the ForeSight cerebral oximeter. MEASUREMENTS AND MAIN RESULTS: The primary assessment tool was the Postoperative Quality of Recovery Scale. Delirium was assessed using the Confusion Assessment Method. Of the 117 patients analyzed in the study, 60 of the patients desaturated below a cerebral oximetry level of 65% for a minimum of 3 minutes (51.3%). Patients who desaturated were significantly less likely to have cognitive recovery in the immediate postoperative period (p = 0.012), which did not persist in the postoperative period beyond day 0. Patients who desaturated also were more likely to have delirium (p = 0.048, odds ratio 2.81 [95% CI 1.01-7.79]) and longer length of stay (relative duration 1.35, 95% CI 1.05-1.73; p = 0.020). CONCLUSIONS: Intraoperative cerebral oxygen desaturations, frequent during one-lung ventilation, are associated significantly with worse early cognitive recovery, high risk of postoperative delirium, and prolonged length of stay. Large interventional studies on cerebral oximetry in the thoracic operating room are warranted.

Deferred Action for Childhood Arrivals (DACA) medical students - an examination of their journey and experiences as medical students in limbo.

BACKGROUND: Although the value of DACA medical students has been hypothesized, no data are available on their contribution to US healthcare. While the exact number of DACA recipients in medical school is unknown, DACA medical students are projected to represent an increasing proportion of physicians in the future. The current literature on DACA students has not analyzed the experiences of these students. METHODS: A mixed-methods study on the career intentions and experiences of DACA medical students was performed utilizing survey data and in-depth interviews. The academic performance of a convenience sample of DACA medical students was compared to that of matriculated medical students from corresponding medical schools, national averages, and first-year residents according to specialty. RESULTS: Thirty-three DACA medical students completed the survey and five participated in a qualitative interview. The average undergraduate GPA (SD) of the DACA medical student sample was 3.7 (0.3), the same as the national GPA of 2017-2018 matriculated medical students. The most common intended residency programs were Internal Medicine (27.2%), Emergency Medicine (15.2%), and Family Medicine (9.1%). In interviews, DACA students discussed their motivation for pursuing medicine, barriers and facilitators that they faced in attending medical school, their experiences as medical students, and their future plans. CONCLUSIONS: The intent of this sample to pursue medical specialties in which there is a growing need further exemplifies the unique value of these students. It is vital to protect the status of DACA recipients and realize the contributions that DACA physicians provide to US healthcare.

Serum cotinine levels and nicotine addiction potential of e-cigarettes: an NHANES analysis.

This study aims to compare serum cotinine levels in e-cigarette and combustible cigarette smokers, in an attempt to quantify the potential chronic nicotine addiction risk that e-cigarettes pose. We analyzed 428 participants in 2015-2016 NHANES: 379 (87.03%) smoked combustible cigarettes alone and 49 (12.97%) smoked e-cigarettes. Serum cotinine levels were measured by isotope-dilution high-performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometric method with a detection limit of 0.015 ng/ml. Electronic cigarette smokers were younger than combustible cigarette smokers (mean age 36.79 versus 42.69 years, P = 0.03), more likely to be male (64.93% versus 48.32%, P = 0.09) and significantly less likely to live with other smokers (50.17% versus 90.07%, P < 0.01). Serum cotinine levels increased linearly with self-reported days of smoking in both electronic cigarette and combustible cigarette smokers, after accounting for living with a smoker. The analysis of the subgroup who reported daily use show non-statistically significantly higher serum cotinine levels in electronic cigarette smokers versus combustible cigarette smokers (ß adj = 52.50, P = 0.10). This analysis of recent US data demonstrates that electronic cigarettes expose users to nicotine levels proportionate to, and potentially higher than combustible cigarettes, and thus pose a serious risk of chronic nicotine addiction. This could be particularly relevant in otherwise tobacco naive individuals; future risk of tobacco-related dependence, addiction and relapse, as well as of tobacco-related cancers in these subjects needs to be investigated.

Racial Disparities in Resection of Early Stage Non-Small Cell Lung Cancer: Variability Among Surgeons.

BACKGROUND: Racial disparities in resection of non-small cell lung cancer (NSCLC) are well documented. Patient-level and system-level factors only partially explain these findings. Although physician-related factors have been suggested as mediators, empirical evidence for their contribution is limited. OBJECTIVE: To determine if racial disparities in receipt of thoracic surgery persisted after patients had a surgical consultation and whether there was a physician contribution to disparities in care. METHODS: The authors identified 19,624 patients with stage I-II NSCLC above 65 years of age from the Surveillance-Epidemiology and End-Results-Medicare database. They studied black and white patients evaluated by a surgeon within 6 months of diagnosis. They assessed for racial differences in resection rates among surgeons using hierarchical linear modeling. Our main outcome was receipt of NSCLC resection. A random intercept was included to test for variability in resection rates across surgeons. Interaction between patient race and the random surgeon intercept was used to evaluate for heterogeneity between surgeons in resection rates for black versus white patients. RESULTS: After surgical consultation, black patients were less likely to undergo resection (adjusted odds ratio, 0.57; 95% confidence interval, 0.47-0.69). Resection rates varied significantly between surgeons (P<0.001). A significant interaction between the surgeon intercept and race (P<0.05) showed variability beyond chance across surgeons in resection rates of black versus white patients. When the model included thoracic surgery specifalization the physician contribution to disparities in care was decreased. CONCLUSIONS: Racial disparities in resection of NSCLC exist even among patients who had access to a surgeon. Heterogeneity between surgeons in resection rates between black and white patients suggests a physician's contribution to observed racial disparities. Specialization in thoracic surgery attenuated this contribution.

An overview of existing mesothelioma registries worldwide, and the need for a US Registry.

The association between asbestos exposure, mainly in occupational settings, and malignant mesothelioma has been well established; this has prompted several countries to establish mesothelioma epidemiologic surveillance programs often at the request of national agencies. This review compares currently existing mesothelioma registries worldwide to develop a concept model for a US real-time case capture mesothelioma registry. Five countries were identified with a mesothelioma specific registry, including Italy, France, UK, Australia, and South Korea. All, except the UK, used interviews to collect exposure data. Linkage with the national death index was available or was in future plans for all registries. The registries have limited information on treatment, quality of life, and other patient-centered outcomes such as symptoms and pain management. To thoroughly collect exposure data, "real-time" enrollment is preferable; to maximize the capture of mesothelioma cases, optimal coverage, and a simplified consent process are needed.

Biomarkers for malignant pleural mesothelioma: a meta-analysis.

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.

Prognostic factors of survival in patients with malignant pleural mesothelioma: an analysis of the National Cancer Database.

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.