BACKGROUND:The aim of this study was to implement and prospectively validate a previously published decision-aid tool to guide ordering of preoperative type and screen (preT&S) tests. STUDY DESIGN:In this interrupted time-series quasi-experimental study, we implemented a decision-aid tool for patients undergoing elective thoracic surgery at a single academic institution. Data were collected 6 months before and prospectively after implementation. The tool, a previously published nomogram, predicts the need for a preT&S using age, BMI, planned operation, approach, and preoperative hemoglobin. We excluded patients who had previous transfusions, neoadjuvant therapy, redo operations, and/or inpatient consults. We validated the tool using multivariable logistic regression, regression discontinuity, c-index, sensitivity, predictive values, and cost savings. RESULTS:One hundred seventy-seven consecutive patients met the inclusion criteria. Eighty-eight were after implementation and 89 patients were before implementation. No differences were observed between the groups in terms of age, sex, BMI, comorbidities, approach, or preoperative hemoglobin (all p > 0.05). Overall transfusion rates were similar (6.8% vs 6.7%; p > 0.99); however, the rate of ordering preT&S was reduced significantly (94.4% vs 60.2%; p < 0.001). At our institution, the decision-aid tool resulted in cost savings of $25,048 over 6 months alone. With a c-index of 0.977, our validation demonstrated 100% sensitivity, 90.3% specificity, and 100% negative predictive value. CONCLUSIONS:Implementation and validation of the preT&S nomogram proved feasible, accurate, and resulted in reducing unnecessary testing and costs before elective noncardiac thoracic surgery. Wider implementation has the potential for substantial cost savings.

The symptomatic burden of malignant pleural mesothelioma (MPM) remains unsurmountable due to not only the insidious nature of its development and abrupt nature of progression, but also due to our relatively limited capabilities to treat it or even slow down its progress and the associated toll such a disease has on an individual's overall quality of life (QoL). The majority of cases are linked to occupational asbestos exposure and arise after a latency period of up to 40 years. Overall survival (OS) drastically varies across studies and treatments, with pooled analyses approximating 13 months post-diagnosis median survival and 10% 5-year survival. As a result of its very grim prognosis and significant deterioration in QoL, treatment strategies began to incorporate the effects of a particular treatment on a patient's QoL. Treatment is often multimodal and consists of surgery, chemotherapy, and radiotherapy (RT). Recent investigations have utilized standardized QoL measurement tools, such as the Lung Cancer Symptom Scale for mesothelioma (LCSS-Meso) and the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), to make studies more comparable so treatments and their effects can be better understood and expanded on. Overall, surgery remains the mainstay of therapy with recent studies finding pleurectomy and decortication leads to improved QoL when compared to extrapleural pneumonectomy (EPP). Chemotherapy and immunotherapy are the most rapidly advancing segment of trimodality therapy due to technological advances which have improved development, synthesis, administration, and efficacy. RT's impact on QoL continues to be debated despite its significant palliative potential due to a high risk of radiation toxicity even after approach, dose, and timing modifications. Given the complexities in MPM treatment, understanding the standardized data generated by these questionnaires and investigating their generalizability in assessing patient QoL will be crucial in the advancement of MPM treatment.

Supplementary Figure 5 from Paxillin Is a Target for Somatic Mutations in Lung Cancer: Implications for Cell Growth and Invasion

Supplementary Table 3 from Paxillin Is a Target for Somatic Mutations in Lung Cancer: Implications for Cell Growth and Invasion

Supplementary Figure 1 from Paxillin Is a Target for Somatic Mutations in Lung Cancer: Implications for Cell Growth and Invasion

Background:Limited data exists for robotic chest wall resection; we report institutional and national experience of robotic chest wall resection.Methods:In this comparative retrospective case series we describe patients who underwent robotic chest wall resection at our institution and enrich this case series with data from the National Cancer Database (NCDB). We describe our preoperative workup, operative technique, and postoperative care. Outcomes included conversion to open, length of stay, readmissions, and 30- and 90-day mortality. The results are descriptively reported and compared.Results:We describe 6 patients institutionally and 96 NCDB patients. At our institution 66.7% were males, median age was 70.0 (range, 39-91) years, and 50% were primary chest wall tumors. Median tumor size was 5.25 (range, 2.3-8.3) cm. Outcomes were as follows: no open conversions, median length of stay 3 (range, 1-6) days, no unplanned 30-day readmissions or 90-day mortality. In the NCDB, 55.2% were males with median age of 68.5 (range, 30-89) years. Median tumor size was 3.90 (range, 2.4-6.0) cm. NCDB outcomes were as follows: 18.8% open conversion, median length of stay 7 (range, 5-10) days, 3.1% unplanned 30-day readmission, and 8.3% 90-day mortality. Our institutional case series had 18.0 months median follow-up (range, 6-54 months) with no functional deficits. Median survival in NCDB was 49.6 months.Conclusions:Robotic chest wall resection is feasible and is performed nationally with acceptable short- and long-term outcomes. Our institutional experience reports our technique, resultant short hospital stay, and excellent functional outcomes.

Supplementary Table 4 from Paxillin Is a Target for Somatic Mutations in Lung Cancer: Implications for Cell Growth and Invasion

PURPOSE:Lung cancer is one of the most common and the deadliest malignancy globally.Thromboembolic events have been associated with increased mortality and adverse outcomes.This study compared the levels of thrombo-inflammatory and oxidative stress biomarkers in patients with non-small cell lung cancer (NSCLC) to normal human population (NHP) and investigated the association between thrombo-inflammatory and oxidative stress-related biomarker levels. METHODS:After obtaining written informed consent, pre-operative plasma samples of 49 patients with pathologically confirmed NSCLC were obtained in accordance with an IRB-approved protocol.Control samples were obtained from 34 healthy individuals.Thrombo-inflammation and oxidative stress-related plasma biomarkers were determined by enzyme-linked immunosorbent assay. RESULTS:Comparison of plasma biomarker levels revealed tissue plasminogen activator (tPA) to be significantly higher in NSCLC patients (p¼0.011) and urokinase-type plasminogen activator (uPA) levels to be significantly higher in NHP (p¼0.009).NSCLC patient plasma also demonstrated significantly higher levels of nitrotyrosine and myeloperoxidase (MPO) (p¼0.002 and p¼0.012, respectively).Among NSCLC patients, tPA and uPA plasma levels demonstrated significant correlation (r¼0.328,p¼0.005).Correlations were also observed between thrombin activatable fibrinolysis inhibitor (TAFI) and factor IX (FIX) levels (r¼0.481,p<0.001) and endogenous glycosaminoglycans and MPO levels (r¼0.386,p¼0.006).Linear regression analysis found TAFI to be an independent predictor of FIX levels (p¼0.006,OR 0.454).CONCLUSIONS: Levels of tPA, nitrotyrosine, and MPO are significantly elevated, while the levels of uPA are lower in NSCLC patients relative to NHP.Additionally, we found positive correlations between tPA and uPA, as well as between TAFI and FIX plasma levels in NSCLC patients.These findings also underscore the fibrinolytic deficit in NSCLC. CLINICAL IMPLICATIONS:As oxidative stress is an important factor influencing clinical course of patients with NSCLC and due to the fact that these patients have a significantly increased risk for thromboembolic events, biomarkers related to these two pathophysiologic conditions chould be included in regular management of patients with NSCLC.

e15030 Background: Interplay between oxidative stress and inflammation play major role in the development and progression of various malignancies. As one of the most common and the deadliest malignancy, lung cancer has a prominent vicious cycle of oxidative stress and immune response. The aim of this study is to examine the inter-relationship between basic oxidative stress and inflammation-related plasma biomarkers in patients with non-small cell lung cancer (NSCLC) undergoing surgical resection procedure. Methods: After obtaining informed consent, pre-operative plasma levels of alpha-fetoprotein, nitrotyrosine, urokinase-type plasminogen activator, and myeloperoxidase (MPO) as oxidative stress-related biomarkers were determined in 49 patients with diagnosed NSCLC. In the same patient group, plasma levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), interferon gamma, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and epidermal growth factor were also evaluated. Control samples were obtained from 34 healthy individuals. Plasma biomarkers were determined by enzyme-linked immunosorbent assay. Applicable statistical methods were used to analyze the data. Results: Positive correlation was observed between MPO and levels of the following inflammation-related biomarkers: IL-6 (r = 0.397, p = 0.007), VEGF (r = 0.494, p = 0.001), TNF-α (r = 0.348, p = 0.019), and MCP-1 (r = 0.377, p = 0.011). Biomarkers showing significance in correlation analysis were further analyzed by linear logistic regression in order to determine presence and strength of causality in each direction (oxidative stress to inflammation and inflammation to oxidative stress). IL-6 and VEGF were observed as a predictors of MPO levels (B = 0.334, p = 0.031, and B = 0.391, p = 0.039, respectively). Furthermore, causality was observed in the opposite direction as well. MPO levels were shown as a slightly better predictor of both IL-6 and VEGF plasma levels (B = 0.349, p = 0.007, and B = 0.433, p = 0.001, respectively), but also as a predictor of TNF-α and MCP-1 levels (B = 0.193, p = 0.019, and B = 0.217, p = 0.011, respectively). Conclusions: Conclusion: These studies showed a strong correlation between measured oxidative stress-related and inflammatory biomarkers. Furthermore, these observations underscore the importance of oxidative stress in the pathogenesis of lung cancer.

Supplementary Table 2 from Paxillin Is a Target for Somatic Mutations in Lung Cancer: Implications for Cell Growth and Invasion

BACKGROUND In December 2013 the US Preventative Services Task Force (USPSTF) recommended annual lung cancer screening for high-risk patients. The Centers for Medicare & Medicaid Services (CMS) later announced coverage in 2015. The impact of these federal decisions at the population level is unknown.METHODS Using the Surveillance, Epidemiology, and End Results database, we studied changes in lung cancer incidence by stage and linked to US census data to obtain age-adjusted estimates standardized to the US popu-lation. Based on age at diagnosis we stratified patients as age-eligible or age-ineligible for screening. We used difference-in-differences regression to determine the effect of screening on lung cancer incidence by stage.RESULTS For all age groups the incidence of early-stage lung cancer both before and after the USPSTF guidelines remained relatively stable at 12.8 +/- 0.52 and 13.5 +/- 0.92 per 100,000 patients, respectively (P = .068). However the difference-in-differences analysis estimated an absolute increase in the age-adjusted incidence by 3.4 per 100,000 persons in the age-eligible group after the announcement of the guidelines (P = .007). The effect was even larger after the CMS decision (4.3/100,000 persons, P < .001). Similarly there was a 14.2 per 100,000 persons absolute reduction in the incidence of advanced-stage lung cancer (P < .001).CONCLUSIONS The 2013 USPSTF lung cancer screening guidelines and CMS coverage decisions were associated with an increased incidence of early-stage lung cancer and decreased incidence of advance-staged lung cancer at the population level.(Ann Thorac Surg 2023;115:827-34)Published by Elsevier Inc. on behalf of The Society of Thoracic Surgeons

Background: Lung cancer has progressed from an exceedingly rare disease to the leading cause of all cancer-related deaths, a phenomenon largely attributed to the impact of tobacco smoking and resulting global epidemic. Methods: A thorough literature search was conducted to identify relevant factors in the epidemiology of lung cancer with a focus on recent studies and developments that had the most significant impact on the current understanding of lung cancer. Results: Most recent data suggests the global burden of lung cancer is continuing to rise with 2.2 million new cases in 2020 alone. Although no difference is noted among men, a higher rate of lung cancer deaths among women in the industrialized countries are observed compared to developing nations. Incidence and deaths are closely linked to cigarette smoking. Other risk factors include occupational hazards, increasing air pollution with pulmonary infectious diseases and inflammatory conditions, and genetic factors. Tobacco continues to cause approximately 90% of all lung cancer deaths with a markedly wide variety of incidence rates both geographically and between males and females. Lung cancer incidence has been falling in US and UK since 1990 largely due to comprehensive tobacco control programs. In contrast higher rates of cigarette smoking among emerging nations is a concern. The unprecedented, widespread adoption of electronic-cigarette use among adolescents may pose major obstacles in the prevention and treatment of lung cancer. Conclusions: While the vast majority of current lung cancer cases and deaths continue to be caused by tobacco consumption, shifts in population behaviors, geographical location, and potential new causes may alter this distribution. Further work is crucial in order to better understand the risk factors for lung cancer in the modern world so that a more holistic proactive approach, rather than a reactive approach, can be taken.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has changed the landscape of professional activities, emphasizing virtual meetings and social media (SoMe) presence. Whether cardiothoracic programs increased their SoMe presence is unknown. We examined SoMe use and content creation by cardiothoracic surgery programs during the COVID-19 pandemic. Methods: We searched the Accreditation Council for Graduate Medical Education to identify all cardiothoracic surgery residency programs (n = 122), including independent (n = 74), integrated (n = 33), and congenital (n = 15) training programs at 78 US cardiothoracic surgery teaching institutions. We then manually searched Google, Facebook, Instagram, LinkedIn, and Twitter to identify the associated residency and departmental accounts. The timeline for our search was between 10/2021 and 4/2022. March 2020 was used as the starting point for the COVID-19 pandemic. We also contacted the account managers to identify account content creators. The data are descriptively reported and analyzed. Results: Of 137 SoMe accounts from 78 US cardiothoracic surgery teaching institutions, 72 of 137 (52.6%) were on Twitter, 34 of 137 (24.8%) on Facebook, and 31 of 137 (22.6%) on Instagram. Most accounts were departmental accounts (105/137 = 76.6%) versus 32 of 137 (23.4%) training program accounts. Most training program-specific SoMe accounts across all platforms were created after the COVID-19 pandemic, whereas departmental accounts were pre-existing (P < .001). The most pronounced SoMe growth was on Instagram at the training program level, with 91.7% of Instagram accounts created after the pandemic. Trainees are the content creators for 94.4% of residency accounts and 33.3% of departmental accounts. Facebook's presence was stagnant. Congenital training programs did not have a specific SoMe presence. Conclusions: SoMe presence by cardiothoracic surgery training programs and departments has increased during the pandemic. Twitter is the most common platform, with a recent increased trend on Instagram. Trainees largely create content. SoMe education and training pathways may be needed for involved trainees to maximize their benefits.

Malignant pleural mesothelioma is a rare disease with an annual incidence of around 3000 cases a year in the United States. Most cases are caused by asbestos exposure, with a latency period of up to 40 years. Pleural mesothelioma is an aggressive disease process with overall survival of roughly 6-12 months after the time of diagnosis. It is divided into three subtypes: epithelioid, mixed type, and sarcomatoid type, with the epithelioid subtype having the best overall survival. Often, the treatment is multimodality with surgery, chemotherapy, and radiation. The survival benefit is improved but remains marginal. New treatment options involving targeted immune therapies appear to offer some promise. The tumor microenvironment is the ecosystem within the tumor that interacts and influences the host immune system. Understanding this complex interaction and how the host immune system is involved in the progression of the disease process is important to define and guide potential treatment options for this devastating and rare disease.

BACKGROUND Traditionally, neoadjuvant chemoradiation therapy is followed by resection in patients with locally advanced non-small cell lung cancer (NSCLC). The risks and benefits of this approach are not well defined in patients requiring a sleeve lung resection. In this context, we compare the short-and long-term outcomes of neoadjuvant chemotherapy alone vs chemoradiation therapy followed by sleeve lung resection.METHODS We used the National Cancer Database to identify locally advanced NSCLC patients who received chemotherapy-alone or chemoradiation therapy in the neoadjuvant setting, followed by a sleeve lung resection, between 2006 and 2017. Our outcomes of interest were 30-day mortality, 90-day mortality, and overall survival. To minimize confounding by indication, we used propensity score adjustment, logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards models to identify associations.RESULTS Of 176 patients undergoing sleeve lung resection, 92 (52.3%) received neoadjuvant chemotherapy-alone, and 84 (47.7%) received neoadjuvant chemoradiation therapy. Patients in both groups were well balanced in age, sex, race, Charlson-Deyo comorbidity index, insurance status, median income, and education (all P > .05). Similarly, the groups were well balanced in histology, tumor location, and stage (all P > .05). Patients receiving neoadjuvant che-moradiation therapy had higher 90-day mortality (11.96% vs 2.38%, P = .015), and there was no difference in overall survival between the neoadjuvant chemotherapy-alone vs chemoradiation therapy cohorts (P = .621).CONCLUSIONS In this national study of patients with locally advanced resectable NSCLC requiring a sleeve lung resection, neoadjuvant chemoradiation therapy was associated with a 5-fold increase in 90-day mortality without an overall survival benefit over neoadjuvant chemotherapy-alone.(Ann Thorac Surg 2022;114:2041-9) (c) 2022 by The Society of Thoracic Surgeons

Background: Lung cancer has the highest mortality rates and one of the lowest 5-year survival rates amongst cancer types in the world. Although there are constant advancements in treatment, the overall prognosis for lung cancer continues to be poor. In order to achieve early detection and personalized targeted treatment, an effective method is needed to make prognostic and treatment decisions. Methods: A thorough literature search was conducted to identify tumor tissue, blood, and expired breath markers that have been discovered in lung cancer. Articles were chosen by determining main markers holding promise for future clinical use. Results: Data suggests significance in using tumor tissue markers as promising diagnostic, prognostic and predictive of treatment response and outcome. Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) and ROS-1 biomarkers can be used to decide to treat with EGFR-TKI and ALK-TKI, respectively. KRAS and p53 mutations suggest a likelihood of developing EGFR-TKI resistance. And c-MET is showing pertinence in predicting disease recurrence. Blood and expired breath markers are two more novel sources for biomarkers that is gaining more ground in lung cancer research. Circulating tumor cells (CTC) and DNA (ctDNA) were shown to be important markers in lung cancer prognosis and treatment response prediction. Circulating tumor cells suggest negative prognosis and increased likelihood of recurrence, while ctDNA data indicates use in treatment monitoring to help make decisions without keeping patients on disagreeable therapies. Volatile organic compounds (VOC) are the least studied, but investigators have noticed changes in VOC profiles between healthy and lung cancer patients. Blood and expired breath markers continue to be studied as these would be a welcome alternative to invasive biopsies. Recently there had been interest in using specific tumor biomarkers for imaging to localize tumors and determine disease progression. Conclusions: Years of research have elucidated multiple candidates as biomarkers found in tumor tissues, circulation, and even in exhaled air. Although more studies need to be performed on some markers mentioned in this review, such as EGFR, KRAS, ALK, and ROS-1, there is enough evidence for some use of these biomarkers to guide decisions in clinic, as well as evidence for promising future developments.

Objectives: Stereotactic body radiation therapy (SBRT) is an established primary treatment modality in patients with lung cancer who have multiple comorbidities and/or advanced-stage disease. However, its role in otherwise healthy patients with stage I lung cancer is unclear. In this context, we compared the effectiveness of SBRT versus surgery on overall survival using a national database. Methods: We identified all patient with clinical stage I non-small cell lung cancer from the National Cancer Database from 2004 to 2016. We defined otherwise healthy patients as those with a Charlson-Deyo comorbidity index of 0 and whose treatment plan included options for either SBRT or surgery. We further excluded patients who received SBRT due to a contraindication to surgery. We first used propensity score matching and Cox proportional hazard models to identify associations. Next, we fit 2-stage residual inclusion models using an instrumental variables approach to estimate the effects of SBRT versus surgery on long-term survival. We used the hospital SBRT utilization rate as the instrument. Results: Of 25,963 patients meeting all inclusion/exclusion criteria, 5465 (21%) were treated with SBRT. On both Cox proportional hazards modeling and propensityscore matched Kaplan-Meier analysis, surgical resection was associated with improved survival relative to SBRT. In the instrumental-variable-adjusted model, SBRT remained associated with decreased survival (hazard ratio, 2.64; P < .001). Both lobectomy (hazard ratio, 0.17) and sublobar resections (hazard ratio, 0.28) were associated with improved overall survival compared with SBRT (P < .001). Conclusions: In otherwise healthy patients with stage I NSCLC, surgical resection is associated with a survival benefit compared with SBRT. This is true for both lobar and sublobar resections. (JTCVS Open 2022;9:249-61)