Publications by authors named "Eric L Grogan"

69 Publications

Preoperative coronary artery calcifications in veterans predict higher all-cause mortality in early-stage lung cancer: a cohort study.

J Thorac Dis 2021 Mar;13(3):1427-1433

Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Lung cancer patients often have comorbidities that may impact survival. This observational cohort study examines whether coronary artery calcifications (CAC) impact all-cause mortality in patients with resected stage I non-small cell lung cancer (NSCLC).

Methods: Veterans with stage I NSCLC who underwent resection at a single institution between 2005 and 2018 were selected from a prospectively collected database. Radiologists blinded to patient outcomes graded CAC severity (mild, moderate, or severe) in preoperative CT scans using a visual estimation scoring system. Inter-rater reliability was calculated using the kappa statistic. All-cause mortality was the primary outcome. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to compare time-to-death by varying CAC.

Results: The Veteran patients (n=195) were predominantly older (median age of 67) male (98%) smokers (96%). The majority (68%) were pathologic stage IA. Overall, 12% of patients had no CAC, 27% mild, 26% moderate, and 36% severe CAC. Median unadjusted survival was 8.8 years for patients with absent or mild CAC versus 6.3 years for moderate and 5.9 years for severe CAC (P=0.01). The adjusted hazard ratio for moderate CAC was 1.44 (95% CI, 0.85-2.46) and for severe CAC was 1.73 (95% CI, 1.03-2.88; P for trend <0.05).

Conclusions: The presence of severe CAC on preoperative imaging significantly impacted the all-cause survival of patients undergoing resection for stage I NSCLC. This impact on mortality should be taken into consideration by multidisciplinary teams when making treatment plans for patients with early-stage disease.
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http://dx.doi.org/10.21037/jtd-20-2102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024847PMC
March 2021

Establishing a Cohort and a Biorepository to Identify Biomarkers for Early Detection of Lung Cancer: The Nashville Lung Cancer Screening Cohort.

Ann Am Thorac Soc 2021 Jan 5. Epub 2021 Jan 5.

Vanderbilt University Medical Center, 12328, Medicine, Nashville, Tennessee, United States.

Rationale: A prospective longitudinal cohort of individuals at high-risk of developing lung cancer was established to build a biorepository of carefully annotated biological specimens and low-dose computed tomography (LDCT) chest images for derivation and validation of candidate biomarkers for early detection of lung cancer.

Objective: The goal of this study is to characterize individuals with high-risk for lung cancer, accumulating valuable biospecimens and LDCT chest scan longitudinally over five years.

Methods: Participants 55-80 years of age and with a 5-year estimated risk of developing lung cancer greater than 1.5% were recruited and enrolled from clinics at Vanderbilt University Medical Center, the Veteran Affairs Medical Center, and Meharry Medical Center. Individual demographic characteristics were assessed via questionnaire at baseline. Participants underwent a LDCT scan, spirometry, sputum cytology, and research bronchoscopy at the time of enrollment. Participants will be followed yearly for five years. Positive LDCT scans are followed-up according to standard of care. The clinical, imaging and biospecimen data are collected prospectively and stored in a biorepository. Participants are offered smoking cessation counseling at each study visit.

Results: A total of 480 participants were enrolled at study baseline and consented to sharing of their data and biospecimens for research. Participants are followed with yearly clinic visits to collect imaging data and biospecimens. To date, a total of 19 cancers (13 adenocarcinomas, 4 squamous cell carcinoma, 1 large cell neuroendocrine and 1 small cell lung cancer) have been identified.

Conclusion: We established a unique prospective cohort of individuals at high-risk for lung cancer, enrolled at three institutions for which full clinical data, well-annotated LDCT and biospecimens are being collected longitudinally. This repository will allow for the derivation of independent validation of clinical, imaging and molecular biomarkers of risk or diagnosis of lung cancer. Clinical trial registered with ClinicalTrials.gov (NCT01475500).
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http://dx.doi.org/10.1513/AnnalsATS.202004-344OCDOI Listing
January 2021

Cost-Effectiveness Analysis of Fibrinolysis versus Thoracoscopic Decortication for Early Empyema.

Ann Thorac Surg 2020 Nov 27. Epub 2020 Nov 27.

Vanderbilt University Medical Center, Nashville, TN; Tennessee Valley Healthcare System, Nashville, TN. Electronic address:

Background: Surgical decortication is recommended by national guidelines for management of early empyema, but intrapleural fibrinolysis is frequently used as a first-line therapy in clinical practice. This study compared the cost effectiveness of video-assisted thoracoscopic surgery (VATS) decortication with intrapleural fibrinolysis for early empyema.

Methods: A decision analysis model was developed. The base clinical case was a 65-year-old male with early empyema treated either by VATS decortication or intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease. The likelihood of key outcomes occurring was derived from the literature. Medicare diagnosis-related groups and manufacturers' drug prices were used for cost estimates. Successful treatment was defined as complete or near-complete resolution of empyema on imaging. Effectiveness was defined as health utility one-year post-empyema.

Results: Intrapleural tPA and deoxyribonuclease was more cost-effective than VATS decortication for treating early empyema for the base scenario. Surgical decortication had a slightly lower cost than fibrinolysis ($13,345 vs $13,965), but fibrinolysis had a marginally higher effectiveness at one year (health utility of 0.80 vs. 0.71) resulting in fibrinolysis being the more cost-effective option. Sensitivity analyses found that fibrinolysis as the initial therapy was more cost-effective when the probability of success was greater than 60% or the initial cost was less than $13,000.

Conclusions: Surgical decortication and intrapleural fibrinolysis have nearly equivalent cost-effectiveness for early empyema in patients that can tolerate both procedures. Surgeons should consider patient-specific factors as well as the cost and effectiveness of both modalities when deciding the initial treatment for early empyema.
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http://dx.doi.org/10.1016/j.athoracsur.2020.11.005DOI Listing
November 2020

Mortality for Robotic- vs Video-Assisted Lobectomy-Treated Stage I Non-Small Cell Lung Cancer Patients.

JNCI Cancer Spectr 2020 Oct 15;4(5):pkaa028. Epub 2020 Apr 15.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

Background: To address the US Food and Drug Administration's recent safety concern on robotic surgery procedures, we compared short- and long-term mortality for stage I non-small cell lung cancer (NSCLC) patients treated by robotic-assisted thoracoscopic surgical lobectomy (RATS-L) vs video-assisted thoracoscopic surgical lobectomy (VATS-L).

Methods: From the National Cancer Database, we identified 18 908 stage I NSCLC patients who underwent RATS-L or VATS-L as the primary operation from 2010 to 2014. Cox proportional hazards models were used to estimate hazard ratios (HRs) for short- and long-term mortality using unmatched and propensity score-matched analyses. All statistical tests were 2-sided.

Results: Patients treated by RATS-L had higher 90-day mortality than those with VATS-L (6.6% vs 3.8%, = .03) if conversion to open thoracotomy occurred. After excluding first-year observation, multiple regression analyses showed RATS-L was associated with increased long-term mortality, compared with VATS-L, in cases with tumor size 20 mm or less: hazard ratio (HR) = 1.33 (95% confidence interval [CI] = 1.15 to 1.55), HR = 1.36 (95% CI = 1.17 to 1.58), and HR = 1.33 (95% CI = 1.11 to 1.61) for unmatched, N:1 matched, and 1:1 matched analyses, respectively, in the intention-to-treat analysis. Among patients without conversion to an open thoracotomy, the respective hazard ratios were 1.19 (95% CI = 1.10 to 1.29), 1.19 (95% CI = 1.10 to 1.29), and 1.17 (95% CI = 1.06 to 1.29). Similar associations were observed when follow-up time started 18 or 24 months postsurgery. No statistically significant mortality difference was found for patients with tumor size of greater than 20 mm. These associations were not related to case volume of VATS-L or RATS-L performed at treatment institutes.

Conclusions: Patients with small (≤20 mm) stage I NSCLC treated with RATS-L had statistically significantly higher long-term mortality risk than VATS-L after 1 year postsurgery.
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http://dx.doi.org/10.1093/jncics/pkaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660043PMC
October 2020

Modeling the impact of delaying surgery for early esophageal cancer in the era of COVID-19.

Surg Endosc 2020 Nov 2. Epub 2020 Nov 2.

Department of Surgery, Tennessee Valley Healthcare System, Nashville, TN, USA.

Background: Surgical society guidelines have recommended changing the treatment strategy for early esophageal cancer during the novel coronavirus (COVID-19) pandemic. Delaying resection can allow for interim disease progression, but the impact of this delay on mortality is unknown. The COVID-19 infection rate at which immediate operative risk exceeds benefit is unknown. We sought to model immediate versus delayed surgical resection in a T1b esophageal adenocarcinoma.

Methods: A decision analysis model was developed, and sensitivity analyses performed. The base case was a 65-year-old male smoker presenting with cT1b esophageal adenocarcinoma scheduled for esophagectomy during the COVID-19 pandemic. We compared immediate surgical resection to delayed resection after 3 months. The likelihood of key outcomes was derived from the literature where available. The outcome was 5-year overall survival.

Results: Proceeding with immediate esophagectomy for the base case scenario resulted in slightly improved 5-year overall survival when compared to delaying surgery by 3 months (5-year overall survival 0.74 for immediate and 0.73 for delayed resection). In sensitivity analyses, a delayed approach became preferred when the probability of perioperative COVID-19 infection increased above 7%.

Conclusions: Immediate resection of early esophageal cancer during the COVID-19 pandemic did not decrease 5-year survival when compared to resection after 3 months for the base case scenario. However, as the risk of perioperative COVID-19 infection increases above 7%, a delayed approach has improved 5-year survival. This balance should be frequently re-examined by surgeons as infection risk changes in each hospital and community throughout the COVID-19 pandemic.
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http://dx.doi.org/10.1007/s00464-020-08101-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605488PMC
November 2020

Modeling the Impact of Delaying Bariatric Surgery due to COVID-19: a Decision Analysis.

Obes Surg 2021 03 26;31(3):1387-1391. Epub 2020 Oct 26.

Department of Thoracic Surgery, Vanderbilt University Medical Center, 609 Oxford House, 1313 21st Ave. South, Nashville, TN, 37232, USA.

We developed a decision analysis model to evaluate risks and benefits of delaying scheduled bariatric surgery during the novel coronavirus disease (COVID-19) pandemic. Our base case was a 45-year-old female with diabetes and a body mass index of 45 kg/m. We compared immediate with delayed surgery after 6 months to allow for COVID-19 prevalence to decrease. We found that immediate and delayed bariatric surgeries after 6 months resulted in similar 20-year overall survival. When the probability of COVID-19 infection exceeded 4%, then delayed surgery improved survival. If future COVID-19 infection rates were at least half those in the immediate scenario, then immediate surgery was favored and local infection rates had to exceed 9% before surgical delay improved survival. Surgeons should consider local disease prevalence and patient comorbidities associated with increased mortality before resuming bariatric surgery programs.
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http://dx.doi.org/10.1007/s11695-020-05054-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587518PMC
March 2021

Modeling the Impact of Delaying the Diagnosis of Non-Small Cell Lung Cancer during COVID-19.

Ann Thorac Surg 2020 Oct 19. Epub 2020 Oct 19.

Vanderbilt University Medical Center, Nashville, TN; Department of Thoracic Surgery; Tennessee Valley Healthcare System, Nashville, TN; Department of Surgery. Electronic address:

Background: The novel coronavirus (COVID-19) pandemic has led surgical societies to recommend delaying diagnosis and treatment of suspected lung cancer in lesions <2 cm. Delaying diagnosis can lead to disease progression, but the impact of this delay on mortality is unknown. The COVID-19 infection rate at which immediate operative risk exceeds benefit is unknown. We sought to model immediate versus delayed surgical resection in a suspicious lung nodule <2 cm.

Methods: A decision analysis model was developed, and sensitivity analyses performed. The base case was a 65-year-old male smoker with COPD presenting for surgical biopsy of 1.5-2.0 cm lung nodule highly suspicious for cancer during the COVID-19 pandemic. We compared immediate surgical resection to delayed resection after three months. The likelihood of key outcomes was derived from the literature where available. The outcome was 5-year overall survival.

Results: Immediate surgical resection resulted in a similar but slightly higher 5-year overall survival when compared to delayed resection (0.77 versus 0.74), due to the risk of disease progression. However, if the probability of acquired COVID-19 infection is greater than 13%, delayed resection is favorable (0.74 vs 0.73).

Conclusions: Immediate surgical biopsy of lung nodules suspicious for cancer in hospitals with low COVID-19 prevalence likely results in improved 5-year survival. However, as the risk of perioperative COVID-19 infection increases above 13%, a delayed approach has similar or improved survival. This balance should be frequently re-examined at each healthcare facility throughout the curve of the pandemic.
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http://dx.doi.org/10.1016/j.athoracsur.2020.08.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571353PMC
October 2020

Preparing for Bundled Payments: Impact of Complications Post-Coronary Artery Bypass Grafting on Costs.

Ann Thorac Surg 2021 04 5;111(4):1258-1263. Epub 2020 Sep 5.

Department of Cardiac Surgery, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

Background: Bundled payments for coronary artery bypass grafting (CABG) provide a single reimbursement for care provided from admission through 90 days post-discharge. We aim to explore the impact of complications on total institutional costs, as well as the drivers of high costs for index hospitalization.

Methods: We linked clinical and internal cost data for patients undergoing CABG from 2014 to 2017 at a single institution. We compared unadjusted average variable direct costs, reporting excess cost from an uncomplicated baseline. We stratified by The Society of Thoracic Surgeons preoperative risk and quality outcome measures as well as value-based outcomes (readmission, post-acute care utilization). We performed multivariable linear regression to evaluate drivers of high costs, adjusting for preoperative and intraoperative characteristics and postoperative complications.

Results: We reviewed 1789 patients undergoing CABG with an average of 2.7 vessels (SD 0.89). A significant proportion of patients were diabetic (51.2%) and obese (mean body mass index 30.6, SD 6.1). Factors associated with increased adjusted costs were preoperative renal failure (P = .001), diabetes (P = .001) and body mass index (P = .05), and postoperative stroke (P < .001), prolonged ventilation (P < .001), rebleeding requiring reoperation (P < .001) and renal failure (P < .001) with varying magnitude. Preoperative ejection fraction and insurance status were not associated with increased adjusted costs.

Conclusions: Preoperative characteristics had less of an impact on costs post-CABG than postoperative complications. Postoperative complications vary in their impact on internal costs, with reoperation, stroke, and renal failure having the greatest impact. In preparation for bundled payments, hospitals should focus on understanding and preventing drivers of high cost.
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http://dx.doi.org/10.1016/j.athoracsur.2020.06.105DOI Listing
April 2021

Validation of Histoplasmosis Enzyme Immunoassay to Evaluate Suspicious Lung Nodules.

Ann Thorac Surg 2021 02 16;111(2):416-420. Epub 2020 Jul 16.

Vanderbilt University Medical Center, Nashville, Tennessee; Tennessee Valley Healthcare System, Nashville, Tennessee.

Background: Granulomas caused by infectious lung diseases can present as indeterminate pulmonary nodules (IPN). This study aims to validate an enzyme immunoassay (EIA) for Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) for diagnosing benign IPN in areas with endemic histoplasmosis.

Methods: Prospectively collected serum samples from patients at Vanderbilt University Medical Center (VUMC [n = 204]), University of Pittsburgh Medical Center (n = 71), and University of Cincinnati (n = 51) with IPN measuring 6 to 30 mm were analyzed for Histoplasma IgG and IgM with EIA. Diagnostic test characteristics were compared with results from the VUMC pilot cohort (n = 127). A multivariable logistic regression model was developed to predict granuloma in IPN.

Results: Cancer prevalence varied by cohort: VUMC pilot 60%, VUMC validation 65%, University of Pittsburgh Medical Center 35%, and University of Cincinnati 75%. Across all cohorts, 19% of patients had positive IgG titers, 5% had positive IgM, and 3% had positive both IgG and IgM. Of patients with benign disease, 33% were positive for at least one antibody. All patients positive for both IgG and IgM antibodies at acute infection levels had benign disease (n = 13), with a positive predictive value of 100%. The prediction model for granuloma in IPN demonstrated an area under the receiver-operating characteristics curve of 0.84 and Brier score of 0.10.

Conclusions: This study confirmed that Histoplasma EIA testing can be useful for diagnosing benign IPN in areas with endemic histoplasmosis in a population at high risk for lung cancer. Integrating Histoplasma EIA testing into the current diagnostic algorithm where histoplasmosis is endemic could improve management of IPN and potentially decrease unnecessary invasive biopsies.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.101DOI Listing
February 2021

The Society of Thoracic Surgeons Composite Score Rating for Pulmonary Resection for Lung Cancer.

Ann Thorac Surg 2020 03 2;109(3):848-855. Epub 2019 Nov 2.

Department of Surgery, Washington University School of Medicine, St Louis, Missouri.

Background: The Society of Thoracic Surgeons (STS) General Thoracic Surgery Database (GTSD) has developed composite quality measures for lobectomy and esophagectomy. This study sought to develop a composite measure including all resections for lung cancer.

Methods: The STS lung cancer composite score is based on 2 outcomes: risk-adjusted mortality and morbidity. GTSD data were included from January 2015 to December 2017. "Star ratings" were created for centers with 30 or more cases by using 95% Bayesian credible intervals. The Bayesian model was performed with and without inclusion of the minimally invasive approach to assess the impact of approach on the composite measure.

Results: The study population included 38,461 patients from 256 centers. Overall operative mortality was 1.3% (495 of 38,461). The major complication rate was 7.9% (3045 of 38,461). The median number of nodes examined was 10 (interquartile range, 5 to 16); the median number of nodal stations sampled was 4 (interquartile range, 3 to 5). Positive resection margins were identified in 3.7% (1420 of 38,461). A total of 214 centers with 30 or more cases were assigned star ratings. There were 7 1-star, 194 2-star, and 13 3-star programs; 70.6% of resections were performed through a minimally invasive approach. Inclusion of minimally invasive approach, which was adjusted for in previous models, altered the star ratings for 3% (6 of 214) of the programs.

Conclusions: Participants in the STS GTSD perform lung cancer resection with low morbidity and mortality. Lymph node data suggest that participants are meeting contemporary staging standards. There is wide variability among participants in application of minimally invasive approaches. The study found that risk adjustment for approach altered ratings in 3% of participants.
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http://dx.doi.org/10.1016/j.athoracsur.2019.08.114DOI Listing
March 2020

Association of a Lung Screening Program Coordinator With Adherence to Annual CT Lung Screening at a Large Academic Institution.

J Am Coll Radiol 2020 Feb 6;17(2):208-215. Epub 2019 Sep 6.

Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research, Education and Clinical Center (GRECC), Nashville, Tennessee; Department of Internal Medicine/Division of General Internal Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Detection of early-stage lung cancer improves during subsequent rounds of screening with low-dose CT and potentially leads to saving lives with curative treatment. Therefore, adherence to annual lung screening is important. We hypothesized that adherence to annual screening would increase after hiring of a dedicated program coordinator.

Methods: We performed a mixed-methods study in a retrospective cohort of patients who underwent lung screening at our academic institution between January 1, 2014, and March 31, 2018. Patients with baseline lung screening examinations performed between January 1, 2014, and September 30, 2016, with Lung CT Screening Reporting & Data System 1 or 2 scores and a 12-month follow-up recommendation were included. We tracked patient adherence to annual follow-up lung screening over time (before and after hiring of a program coordinator) and conducted a cross-sectional survey of patients nonadherent to annual follow-up to elicit quantitative and qualitative feedback.

Results: Of the 319 patients who completed baseline lung screening with normal results, 189 (59%) were adherent to annual follow-up recommendations and 130 (41%) were nonadherent. Patient adherence varied over time: 21.7% adherence (10 of 46) before hiring a program coordinator and 65.6% adherence (179 of 273) after the program coordinator's hire date. Patients reported the following reasons for nonadherence to annual lung screening: lack of transportation, financial cost, lack of communication by physicians, and lack of current symptoms.

Conclusions: Adherence to annual lung screening after normal baseline studies increased significantly over time. Hiring a full-time program coordinator was likely associated with this increased in adherence.
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http://dx.doi.org/10.1016/j.jacr.2019.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767624PMC
February 2020

Risk Prediction in Clinical Practice: A Practical Guide for Cardiothoracic Surgeons.

Ann Thorac Surg 2019 11 27;108(5):1573-1582. Epub 2019 Jun 27.

Department of Thoracic Surgery, Tennessee Valley Healthcare System, Nashville, Tennessee; Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

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http://dx.doi.org/10.1016/j.athoracsur.2019.04.126DOI Listing
November 2019

Evaluation of USPSTF Lung Cancer Screening Guidelines Among African American Adult Smokers.

JAMA Oncol 2019 Jun 27. Epub 2019 Jun 27.

Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.

Importance: The United States Preventive Services Task Force (USPSTF) recommends low-dose computed tomography screening for lung cancer. However, USPSTF screening guidelines were derived from a study population including only 4% African American smokers, and racial differences in smoking patterns were not considered.

Objective: To evaluate the diagnostic accuracy of USPSTF lung cancer screening eligibility criteria in a predominantly African American and low-income cohort.

Design, Setting, And Participants: The Southern Community Cohort Study prospectively enrolled adults visiting community health centers across 12 southern US states from March 25, 2002, through September 24, 2009, and followed up for cancer incidence through December 31, 2014. Participants included African American and white current and former smokers aged 40 through 79 years. Statistical analysis was performed from May 11, 2016, to December 6, 2018.

Exposures: Self-reported race, age, and smoking history. Cumulative exposure smoking histories encompassed most recent follow-up questionnaires.

Main Outcomes And Measures: Incident lung cancer cases assessed for eligibility for lung cancer screening using USPSTF criteria.

Results: Among 48 364 ever smokers, 32 463 (67%) were African American and 15 901 (33%) were white, with 1269 incident lung cancers identified. Among all 48 364 Southern Community Cohort Study participants, 5654 of 32 463 African American smokers (17%) were eligible for USPSTF screening compared with 4992 of 15 901 white smokers (31%) (P < .001). Among persons diagnosed with lung cancer, a significantly lower percentage of African American smokers (255 of 791; 32%) was eligible for screening compared with white smokers (270 of 478; 56%) (P < .001). The lower percentage of eligible lung cancer cases in African American smokers was primarily associated with fewer smoking pack-years among African American vs white smokers (median pack-years: 25.8 [interquartile range, 16.9-42.0] vs 48.0 [interquartile range, 30.2-70.5]; P < .001). Racial disparity was observed in the sensitivity and specificity of USPSTF guidelines between African American and white smokers for all ages. Lowering the smoking pack-year eligibility criteria to a minimum 20-pack-year history was associated with an increased percentage of screening eligibility of African American smokers and with equitable performance of sensitivity and specificity compared with white smokers across all ages (for a 55-year-old current African American smoker, sensitivity increased from 32.2% to 49.0% vs 56.5% for a 55-year-old white current smoker; specificity decreased from 83.0% to 71.6% vs 69.4%; P < .001).

Conclusions And Relevance: Current USPSTF lung cancer screening guidelines may be too conservative for African American smokers. The findings suggest that race-specific adjustment of pack-year criteria in lung cancer screening guidelines would result in more equitable screening for African American smokers at high risk for lung cancer.
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http://dx.doi.org/10.1001/jamaoncol.2019.1402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604090PMC
June 2019

Developing prediction models for clinical use using logistic regression: an overview.

J Thorac Dis 2019 Mar;11(Suppl 4):S574-S584

Vanderbilt University Medical Center, Nashville, TN, USA.

Prediction models help healthcare professionals and patients make clinical decisions. The goal of an accurate prediction model is to provide patient risk stratification to support tailored clinical decision-making with the hope of improving patient outcomes and quality of care. Clinical prediction models use variables selected because they are thought to be associated (either negatively or positively) with the outcome of interest. Building a model requires data that are computer-interpretable and reliably recorded within the time frame of interest for the prediction. Such models are generally defined as either diagnostic, likelihood of disease or disease group classification, or prognostic, likelihood of response or risk of recurrence. We describe a set of guidelines and heuristics for clinicians to use to develop a logistic regression-based prediction model for binary outcomes that is intended to augment clinical decision-making.
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http://dx.doi.org/10.21037/jtd.2019.01.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465431PMC
March 2019

The Impact of an Interventional Pulmonary Program on Nontherapeutic Lung Resections.

J Bronchology Interv Pulmonol 2019 Oct;26(4):287-289

Department of Surgery, Vanderbilt University Medical Center.

Background: Pulmonary resection can concurrently diagnose and treat known or suspected lung cancer, but is not without risk. Benign resection rates range widely (9% to 40%). We evaluated the impact of an Interventional Pulmonology (IP) program and dedicated Pulmonary Nodule Clinic on surgical benign resection rates at a single institution.

Methods: An IP program was initiated in August 2010 that offered advanced diagnostic techniques and a dedicated Pulmonary Nodule Clinic was opened in August 2013. We retrospectively reviewed all patients who underwent resection for known or suspected lung cancer between 2005 and 2015 at our tertiary referral hospital. Demographics, preoperative tissue diagnoses, surgical procedure, final pathology, and staging were collected. Quarterly benign resection rates were calculated and plotted on a statistical quality control chart (P-Chart) to determine the impact of the IP program and Pulmonary Nodule Clinic on benign resection rates over time.

Results: Of 1112 resections, 209 (19%) were benign. Variation in quarterly benign resection rates decreased after introduction of the IP program in 2010, and a significant (P<0.05) sustained decrease in the quarterly benign resection rate occurred after introduction of the pulmonary nodule clinic in 2013 to a new baseline of 12% compared with 24% before 2010. After introduction of the IP program, mean quarterly preoperative tissue diagnostic rates increased from 45% to 58% (P<0.01).

Conclusion: Integration of an IP program employing advanced diagnostic bronchoscopic techniques has improved preoperative diagnostic rates of suspicious pulmonary nodules and in combination with a pulmonary nodule clinic has resulted in fewer benign resections.
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http://dx.doi.org/10.1097/LBR.0000000000000592DOI Listing
October 2019

Uptake of Video-Assisted Thoracoscopic Lung Resections Within the Veterans Affairs for Known or Suspected Lung Cancer.

JAMA Surg 2019 06;154(6):524-529

Tennessee Valley Healthcare System, Nashville.

Importance: Minimally invasive lobectomy for early-stage lung cancer has become more prevalent. Video-assisted thoracoscopic surgery has lower rates of morbidity, better long-term survival, and equivalent oncologic outcomes compared with thoracotomy. However, little has been published on the use and outcomes of video-assisted thoracoscopic surgery within Veterans Affairs. There is a public assumption that the the Veterans Affairs is slow to adopt new procedures and technologies.

Objective: To determine the uptake of video-assisted thoracoscopic surgery within the Veterans Affairs for patients with known or suspected lung cancer.

Design, Setting, And Participants: In this retrospective cohort study of national Veterans Affairs Corporate Data Warehouse data from January 2002 to December 2015, a total of 11 004 veterans underwent lung resection for known or suspected lung cancer. Data were analyzed from March to November 2018.

Exposures: Open or video-assisted thoracoscopic lobectomy or wedge resection.

Main Outcomes And Measures: Patient demographic characteristics and procedure and diagnosis International Classification of Diseases, Ninth Revision codes were abstracted from Corporate Data Warehouse data.

Results: Of the 11 004 included veterans, 10 587 (96.2%) were male, and the median (interquartile range) age was 66.0 (61.0-72.0) years. Of 11 004 included procedures, 8526 (77.5%) were lobectomies and 2478 (22.5%) were wedge resections. The proportion of video-assisted thoracoscopic lung resections increased steadily from 15.6% in 2002 to 50.6% in 2015. Video-assisted thoracoscopic surgery use by Veterans Integrated Service Networks ranged from 0% to 81.7%, and higher Veterans Integrated Service Network volume was correlated with higher video-assisted thoracoscopic surgery use (Pearson r = 0.35; 95% CI, 0.15-0.52; P < .001). Video-assisted thoracoscopic surgery use and rate of uptake varied widely across Veteran Affairs regions (P < .001 by Wilcoxon signed rank test).

Conclusions And Relevance: Paralleling academic hospitals, most lung resections are now performed in the Veterans Affairs using video-assisted thoracoscopic surgery. More research is needed to identify reasons behind the heterogeneous uptake of video-assisted thoracoscopic surgery across Veterans Affairs regions.
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http://dx.doi.org/10.1001/jamasurg.2019.0035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583397PMC
June 2019

Outcomes of Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation.

Ann Thorac Surg 2019 05 18;107(5):1456-1463. Epub 2019 Feb 18.

Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

Background: Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (BTT) has become a critical component of caring for patients with end-stage lung disease. This study examined outcomes of patients who received ECMO as a BTT.

Methods: Statistical analysis was performed on data gathered retrospectively from the electronic medical records of adult patients who received ECMO as BTT at Columbia University Medical Center from April 2009 through July 2018.

Results: A total of 121 adult patients were placed on ECMO as BTT, and 70 patients (59%) were successfully bridged to lung transplantation. Simplified Acute Physiology Score II, unplanned endotracheal intubation, renal replacement therapy, and cerebrovascular accident were identified as independent predictors of unsuccessful BTT. Ambulation was the only independent predictor of successful BTT (odds ratio, 7.579; 95% confidence interval, 2.158 to 26.615; p = 0.002). Among the 64 patients (91%) who survived to hospital discharge, survival was 88% at 1 year and 83% at 3 years. Propensity matching between BTT and non-BTT lung transplant recipients did not show a significant difference in survival (log-rank = 0.53) despite significant differences in the lung allocation score (median, 92.2 [interquartile range, 89.0 to 94.2] vs 49.6 [interquartile range, 40.6 to 72.3], p < 0.01).

Conclusions: ECMO can be used successfully to bridge patients with end-stage lung disease to lung transplantation. When implemented by an experienced team with adherence to stringent protocols and patient selection, outcomes in BTT patients were comparable to patients who did not receive pretransplant support.
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http://dx.doi.org/10.1016/j.athoracsur.2019.01.032DOI Listing
May 2019

Accuracy of a Novel Histoplasmosis Enzyme Immunoassay to Evaluate Suspicious Lung Nodules.

Cancer Epidemiol Biomarkers Prev 2019 02 19;28(2):321-326. Epub 2018 Oct 19.

Tennessee Valley VA Healthcare System, Nashville, Tennessee.

Background: Granulomas caused by infectious lung diseases present as indeterminate pulmonary nodules (IPNs) on radiography. Newly available serum enzyme immunoassay (EIA) for histoplasmosis has not been studied for the evaluation of IPNs. We investigated serum biomarkers of histoplasmosis antibodies as an indication of benign disease in IPNs from a highly endemic region.

Methods: A total of 152 serum samples from patients presenting with pulmonary nodules ≤30 mm in maximum diameter were analyzed for histoplasmosis antibodies by immunodiffusion and EIA IgG and IgM tests. Serology and FDG-PET/CT scan diagnostic test characteristics were estimated and compared.

Results: Cancer prevalence was 55% ( = 83). Thirty-nine (26%) individuals were positive for IgG histoplasmosis antibodies. Twelve samples were IgM antibody positive. Immunodiffusion serology was similar to IgM antibody results with 13 positive tests. Diagnostic likelihood ratios for benign disease were 0.62, 0.33, and 0.28 for FDG-PET/CT, IgG, and IgM antibodies, respectively. When both IgG and IgM were positive ( = 8), no nodules were cancerous and six were FDG-PET/CT avid.

Conclusions: A positive EIA test for both IgM and IgG strongly suggested histoplasmosis etiology and benign granuloma for 12% of benign nodules arising from a highly endemic region. Presence of either IgG or IgM histoplasma antibodies was associated with benign disease. The EIA test was more sensitive in assessing histoplasma exposure than immunodiffusion serology.

Impact: A new CLIA-certified histoplasmosis antibody EIA test measures histoplasmosis exposure, offers a possible alternative clinical diagnosis for benign IPNs, and may improve IPN evaluation while avoiding harmful invasive biopsies.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363824PMC
February 2019

Defining Proficiency for The Society of Thoracic Surgeons Participants Performing Thoracoscopic Lobectomy.

Ann Thorac Surg 2019 01 28;107(1):202-208. Epub 2018 Sep 28.

Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

Background: Parameters defining attainment and maintenance of proficiency in thoracoscopic video-assisted thoracic surgery (VATS) lobectomy remain unknown. To address this knowledge gap, this study investigated the institutional performance curve for VATS lobectomy by using risk-adjusted cumulative sum (Cusum) analysis.

Methods: Using The Society of Thoracic Surgeons General Thoracic Surgery Database, the study investigators identified centers that had performed a total of 30 or more VATS lobectomies. Major morbidity, mortality, and blood transfusion were deemed primary outcomes, with expected incidence derived from risk-adjusted regression models. Acceptable and unacceptable failure rates for outcomes were set a priori according to clinical relevance and informed by regression model output.

Results: Between 2001 and 2016, 24,196 patients underwent VATS lobectomy at 159 centers with a median volume of 103 (range, 30 to 760). Overall rates of operative mortality, major morbidity, and transfusion were 1% (244 of 24,189), 17.1% (4,145 of 24,196), and 4% (975 of 24,196), respectively. Of the highest-volume centers (≥100 cases), 84% (65 of 77) and 82 % (63 of 77) (p = 0.48) were proficient by major morbidity standards by their 50th and 100th cases, respectively. Similarly, 92% (71 of 77) and 90% (69 of 77) (p = 0.41) of centers showed proficiency by transfusion standards by their 50th and 100th cases, respectively. Three performance patterns were observed: (1) initial and sustained proficiency, (2) crossing unacceptability thresholds with subsequent improved performance; and (3) crossing unacceptability thresholds without subsequent improved performance.

Conclusions: VATS lobectomy outcomes have improved with lower mortality and transfusion rates. The majority of high-volume centers demonstrated proficiency after 50 cases; however, maintenance of proficiency is not ensured. Cusum provides a simple yet powerful tool that can trigger internal audits and performance improvement initiatives.
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http://dx.doi.org/10.1016/j.athoracsur.2018.07.074DOI Listing
January 2019

Mapping Histoplasma capsulatum Exposure, United States.

Emerg Infect Dis 2018 10;24(10):1835-1839

Maps of Histoplasma capsulatum infection prevalence were created 50 years ago; since then, the environment, climate, and anthropogenic land use have changed drastically. Recent outbreaks of acute disease in Montana and Nebraska, USA, suggest shifts in geographic distribution, necessitating updated prevalence maps. To create a weighted overlay geographic suitability model for Histoplasma, we used a geographic information system to combine satellite imagery integrating land cover use (70%), distance to water (20%), and soil pH (10%). We used logistic regression modeling to compare our map with state-level histoplasmosis incidence data from a 5% sample from the Centers for Medicare and Medicaid Services. When compared with the state-based Centers data, the predictive accuracy of the suitability score-predicted states with high and mid-to-high histoplasmosis incidence was moderate. Preferred soil environments for Histoplasma have migrated into the upper Missouri River basin. Suitability score mapping may be applicable to other geographically specific infectious vectors.
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http://dx.doi.org/10.3201/eid2410.180032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154167PMC
October 2018

Long-Term Physical HRQOL Decreases After Single Lung as Compared With Double Lung Transplantation.

Ann Thorac Surg 2018 12 16;106(6):1633-1639. Epub 2018 Aug 16.

Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee; Transplant Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Single lung transplantation (SLT) and double lung transplantation (DLT) are associated with differences in morbidity and mortality, although the effects of transplant type on patient-reported outcomes are not widely reported and conclusions have differed. Previous studies compared mean health-related quality of life (HRQOL) scores but did not evaluate potentially different temporal trajectories in the context of longitudinal follow-up. To address this uncertainty, this study was designed to evaluate longitudinal HRQOL after SLT and DLT with the hypothesis that temporal trajectories differ between SLT and DLT.

Methods: Patients transplanted at a single institution were eligible to be surveyed at 1 month, 3 months, 6 months, and then annually after transplant using the Short Form 36 Health Survey, with longitudinal physical component summary (PCS) and mental component summary (MCS) scores as the primary outcomes. Multivariable mixed-effects models were used to evaluate the effects of transplant type and time posttransplant on longitudinal PCS and MCS after adjusting age, diagnosis, rejection, Lung Allocation Score quartile, and intubation duration. Time by transplant type interaction effects were used to test whether the temporal trajectories of HRQOL differ between SLT and DLT recipients. HRQOL scores were referenced to general population norms (range, 40 to 60; mean, 50 ± 10) using accepted standards for a minimally important difference (½ SD, 5 points).

Results: Postoperative surveys (n = 345) were analyzed for 136 patients (52% male, 23% SLT, age 52 ± 13 years, LAS 42 ± 12, follow-up 37 ± 29 months [range, 0.6 to 133]) who underwent lung transplantation between 2005 and 2016. After adjusting for model covariates, overall posttransplant PCS scores have a significant downward trajectory (p = 0.015) whereas MCS scores remain stable (p = 0.593), with both averaging within general population norms. The time by transplant type interaction effect (p = 0.002), however, indicate that posttransplant PCS scores of SLT recipients decline at a rate of 2.4 points per year over the total observation period compared to DLT. At approximately 60 months, the PCS scores of SLT recipients, but not DLT recipients, fall below general population norms.

Conclusions: The trajectory of physical HRQOL in patients receiving SLT declines over time compared with DLT, indicating that, in the longer term, SLT recipients are more likely to have physical HRQOL scores that fall substantively below general population norms. Physical HRQOL after 5 years may be a consideration for lung allocation and patient counseling regarding expectations when recommending SLT or DLT.
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http://dx.doi.org/10.1016/j.athoracsur.2018.06.072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240480PMC
December 2018

Racial Disparities in Lung Cancer Survival: The Contribution of Stage, Treatment, and Ancestry.

J Thorac Oncol 2018 10 6;13(10):1464-1473. Epub 2018 Jun 6.

Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

Introduction: Lung cancer is a leading cause of cancer-related death worldwide. Racial disparities in lung cancer survival exist between blacks and whites, yet they are limited by categorical definitions of race. We sought to examine the impact of African ancestry on overall survival among blacks and whites with NSCLC cases.

Methods: Incident cases of NSCLC in blacks and whites from the prospective Southern Community Cohort Study (N = 425) were identified through linkage with state cancer registries in 12 southern states. Vital status was determined by linkage with the National Death Index and Social Security Administration. We evaluated the impact of African ancestry (as estimated by using genome-wide ancestry-informative markers) on overall survival by calculating the time-dependent area under the curve (AUC) for Cox proportional hazards models, adjusting for relevant covariates such as stage and treatment. We replicated our findings in an independent population of NSCLC cases in blacks.

Results: Global African ancestry was not significantly associated with overall survival among NSCLC cases. There was no change in model performance when Cox proportional hazards models with and without African ancestry were compared (AUC = 0.79 for each model). Removal of stage and treatment reduced the average time-dependent AUC from 0.79 to 0.65. Similar findings were observed in our replication study.

Conclusions: Stage and treatment are more important predictors of survival than African ancestry is. These findings suggest that racial disparities in lung cancer survival may disappear with similar early detection efforts for blacks and whites.
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http://dx.doi.org/10.1016/j.jtho.2018.05.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153049PMC
October 2018

Communication About the Probability of Cancer in Indeterminate Pulmonary Nodules.

JAMA Surg 2018 04;153(4):353-357

Department of Surgery, Tennessee Valley Healthcare System, Nashville.

Importance: Clinical guidelines recommend that clinicians estimate the probability of malignancy for patients with indeterminate pulmonary nodules (IPNs) larger than 8 mm. Adherence to these guidelines is unknown.

Objectives: To determine whether clinicians document the probability of malignancy in high-risk IPNs and to compare these quantitative or qualitative predictions with the validated Mayo Clinic Model.

Design, Setting, And Participants: Single-institution, retrospective cohort study of patients from a tertiary care Department of Veterans Affairs hospital from January 1, 2003, through December 31, 2015. Cohort 1 included 291 veterans undergoing surgical resection of known or suspected lung cancer from January 1, 2003, through December 31, 2015. Cohort 2 included a random sample of 239 veterans undergoing inpatient or outpatient pulmonary evaluation of IPNs at the hospital from January 1, 2003, through December 31, 2012.

Exposures: Clinician documentation of the quantitative or qualitative probability of malignancy.

Main Outcomes And Measures: Documentation from pulmonary and/or thoracic surgery clinicians as well as information from multidisciplinary tumor board presentations was reviewed. Any documented quantitative or qualitative predictions of malignancy were extracted and summarized using descriptive statistics. Clinicians' predictions were compared with risk estimates from the Mayo Clinic Model.

Results: Of 291 patients in cohort 1, 282 (96.9%) were men; mean (SD) age was 64.6 (9.0) years. Of 239 patients in cohort 2, 233 (97.5%) were men; mean (SD) age was 65.5 (10.8) years. Cancer prevalence was 258 of 291 cases (88.7%) in cohort 1 and 110 of 225 patients with a definitive diagnosis (48.9%) in cohort 2. Only 13 patients (4.5%) in cohort 1 and 3 (1.3%) in cohort 2 had a documented quantitative prediction of malignancy prior to tissue diagnosis. Of the remaining patients, 217 of 278 (78.1%) in cohort 1 and 149 of 236 (63.1%) in cohort 2 had qualitative statements of cancer risk. In cohort 2, 23 of 79 patients (29.1%) without any documented malignancy risk statements had a final diagnosis of cancer. Qualitative risk statements were distributed among 32 broad categories. The most frequently used statements aligned well with Mayo Clinic Model predictions for cohort 1 compared with cohort 2. The median Mayo Clinic Model-predicted probability of cancer was 68.7% (range, 2.4%-100.0%). Qualitative risk statements roughly aligned with Mayo predictions.

Conclusions And Relevance: Clinicians rarely provide quantitative documentation of cancer probability for high-risk IPNs, even among patients drawn from a broad range of cancer probabilities. Qualitative statements of cancer risk in current practice are imprecise and highly variable. A standard scale that correlates with predicted cancer risk for IPNs should be used to communicate with patients and other clinicians.
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http://dx.doi.org/10.1001/jamasurg.2017.4878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910256PMC
April 2018

Assessment of Fluorodeoxyglucose F18-Labeled Positron Emission Tomography for Diagnosis of High-Risk Lung Nodules.

JAMA Surg 2018 04;153(4):329-334

Tennessee Valley Healthcare System, Nashville, Tennessee.

Importance: Clinicians rely heavily on fluorodeoxyglucose F18-labeled positron emission tomography (FDG-PET) imaging to evaluate lung nodules suspicious for cancer. We evaluated the performance of FDG-PET for the diagnosis of malignancy in differing populations with varying cancer prevalence.

Objective: To determine the performance of FDG-PET/computed tomography (CT) in diagnosing lung malignancy across different populations with varying cancer prevalence.

Design, Setting, And Participants: Multicenter retrospective cohort study at 6 academic medical centers and 1 Veterans Affairs facility that comprised a total of 1188 patients with known or suspected lung cancer from 7 different cohorts from 2005 to 2015.

Exposures: 18F fluorodeoxyglucose PET/CT imaging.

Main Outcome And Measures: Final diagnosis of cancer or benign disease was determined by pathological tissue diagnosis or at least 18 months of stable radiographic follow-up.

Results: Most patients were male smokers older than 60 years. Overall cancer prevalence was 81% (range by cohort, 50%-95%). The median nodule size was 22 mm (interquartile range, 15-33 mm). Positron emission tomography/CT sensitivity and specificity were 90.1% (95% CI, 88.1%-91.9%) and 39.8% (95% CI, 33.4%-46.5%), respectively. False-positive PET scans occurred in 136 of 1188 patients. Positive predictive value and negative predictive value were 86.4% (95% CI, 84.2%-88.5%) and 48.7% (95% CI, 41.3%-56.1%), respectively. On logistic regression, larger nodule size and higher population cancer prevalence were both significantly associated with PET accuracy (odds ratio, 1.027; 95% CI, 1.015-1.040 and odds ratio, 1.030; 95% CI, 1.021-1.040, respectively). As the Mayo Clinic model-predicted probability of cancer increased, the sensitivity and positive predictive value of PET/CT imaging increased, whereas the specificity and negative predictive value dropped.

Conclusions And Relevance: High false-positive rates were observed across a range of cancer prevalence. Normal PET/CT scans were not found to be reliable indicators of the absence of disease in patients with a high probability of lung cancer. In this population, aggressive tissue acquisition should be prioritized using a comprehensive lung nodule program that emphasizes advanced tissue acquisition techniques such as CT-guided fine-needle aspiration, navigational bronchoscopy, and endobronchial ultrasonography.
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http://dx.doi.org/10.1001/jamasurg.2017.4495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910279PMC
April 2018

Timeliness of Care and Lung Cancer Tumor-Stage Progression: How Long Can We Wait?

Ann Thorac Surg 2017 Dec 21;104(6):1791-1797. Epub 2017 Oct 21.

Tennessee Valley Healthcare System, Nashville, Tennessee; Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

Background: Timely care of lung cancer is presumed critical, yet clear evidence of stage progression with delays in care is lacking. We investigated the reasons for delays in treatment and the impact these delays have on tumor-stage progression.

Methods: We queried our retrospective database of 265 veterans who underwent cancer resection from 2005 to 2015. We extracted time intervals between nodule identification, diagnosis, and surgical resection; changes in nodule radiographic size over time; final pathologic staging; and reasons for delays in care. Pearson's correlation and Fisher's exact test were used to compare cancer growth and stage by time to treatment.

Results: Median time from referral to surgical evaluation was 11 days (interquartile range, 8 to 17). Median time from identification to therapeutic resection was 98 days (interquartile range, 66 to 139), and from diagnosis to resection, 53 days (interquartile range, 35 to 77). Sixty-eight patients (26%) were diagnosed at resection; the remainder had preoperative tissue diagnoses. No significant correlation existed between tumor growth and time between nodule identification and resection, or between tumor growth and time between diagnosis and resection. Among 197 patients with preoperative diagnoses, 42% (83) had intervals longer than 60 days between diagnosis and resection. Most common reasons for delay were cardiac clearance, staging, and smoking cessation. Larger nodules had fewer days between identification and resection (p = 0.03).

Conclusions: Evaluation, staging, and smoking cessation drive resection delays. The lack of association between tumor growth and time to treatment suggests other clinical or biological factors, not time alone, underlie growth risk. Until these factors are identified, delays to diagnosis and treatment should be minimized.
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http://dx.doi.org/10.1016/j.athoracsur.2017.06.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813822PMC
December 2017

Germline Genetic Variants and Lung Cancer Survival in African Americans.

Cancer Epidemiol Biomarkers Prev 2017 08 15;26(8):1288-1295. Epub 2017 Jun 15.

Department of Thoracic Surgery, Vanderbilt University Medical School, Nashville, Tennessee.

African Americans have the highest lung cancer mortality in the United States. Genome-wide association studies (GWASs) of germline variants influencing lung cancer survival have not yet been conducted with African Americans. We examined five previously reported GWAS catalog variants and explored additional genome-wide associations among African American lung cancer cases. Incident non-small cell lung cancer cases ( = 286) in the Southern Community Cohort Study were genotyped on the Illumina HumanExome BeadChip. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CIs) for overall mortality. Two independent African American studies ( = 316 and 298) were used for replication. One previously reported variant, rs1878022 on 12q23.3, was significantly associated with mortality (HR = 0.70; 95% CI: 0.54-0.92). Replication findings were in the same direction, although attenuated (HR = 0.87 and 0.94). Meta-analysis had a HR of 0.83 (95% CI, 0.71-0.97). Analysis of common variants identified an association between chromosome 6q21.33 and mortality (HR = 0.46; 95% CI, 0.33-0.66). We identified an association between rs1878022 in and lung cancer survival. However, our results in African Americans have a different direction of effect compared with a prior study in European Americans, suggesting a different genetic architecture or presence of gene-environment interactions. We also identified variants on chromosome 6 within the gene-rich HLA region, which has been previously implicated in lung cancer risk and survival. We found evidence that inherited genetic risk factors influence lung cancer survival in African Americans. Replication in additional populations is necessary to confirm potential genetic differences in lung cancer survival across populations. .
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http://dx.doi.org/10.1158/1055-9965.EPI-16-0998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540773PMC
August 2017

68Ga-DOTATATE PET/CT imaging of indeterminate pulmonary nodules and lung cancer.

PLoS One 2017 9;12(2):e0171301. Epub 2017 Feb 9.

Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, United States of America.

Purpose: 18F-FDG PET/CT is widely used to evaluate indeterminate pulmonary nodules (IPNs). False positive results occur, especially from active granulomatous nodules. A PET-based imaging agent with superior specificity to 18F-FDG for IPNs, is badly needed, especially in areas of endemic granulomatous nodules. Somatostatin receptors (SSTR) are expressed in many malignant cells including small cell and non-small cell lung cancers (NSCLCs). 68Ga-DOTATATE, a positron emitter labeled somatostatin analog, combined with PET/CT imaging, may improve the diagnosis of IPNs over 18F-FDG by reducing false positives. Our study purpose was to test this hypothesis in our region with high endemic granulomatous IPNs.

Methods: We prospectively performed 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT scans in the same 30 patients with newly diagnosed, treatment-naïve lung cancer (N = 14) or IPNs (N = 15) and one metastatic nodule. 68Ga-DOTATATE SUVmax levels at or above 1.5 were considered likely malignant. We analyzed the scan results, correlating with ultimate diagnosis via biopsy or 2-year chest CT follow-up. We also correlated 68Ga-DOTATATE uptake with immunohistochemical (IHC) staining for SSTR subtype 2A (SSTR2A) in pathological specimens.

Results: We analyzed 31 lesions in 30 individuals, with 14 (45%) being non-neuroendocrine lung cancers and 1 (3%) being metastatic disease. McNemar's result comparing the two radiopharmaceuticals (p = 0.65) indicates that their accuracy of diagnosis in this indication are equivalent. 68Ga-DOTATATE was more specific (94% compared to 81%) and less sensitive 73% compared to 93%) than 18F-FDG. 68Ga-DOTATATE uptake correlated with SSTR2A expression in tumor stroma determined by immunohistochemical (IHC) staining in 5 of 9 (55%) NSCLCs.

Conclusion: 68Ga-DOTATATE and 18F-FDG PET/CT had equivalent accuracy in the diagnosis of non-neuroendocrine lung cancer and 68Ga-DOTATATE was more specific than 18F-FDG for the diagnosis of IPNs. IHC staining for SSTR2A receptor expression correlated with tumor stroma but not tumor cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171301PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300187PMC
September 2017

Predictors of Major Morbidity or Mortality After Resection for Esophageal Cancer: A Society of Thoracic Surgeons General Thoracic Surgery Database Risk Adjustment Model.

Ann Thorac Surg 2016 Jul 28;102(1):207-14. Epub 2016 May 28.

Department of General Thoracic Surgery, University of Virginia Health System, Charlottesville, Virginia.

Background: The purpose of this analysis was to revise the model for perioperative risk for esophagectomy for cancer utilizing The Society of Thoracic Surgeons General Thoracic Surgery Database to provide enhanced risk stratification and quality improvement measures for contributing centers.

Methods: The Society of Thoracic Surgeons General Thoracic Surgery Database was queried for all patients treated for esophageal cancer with esophagectomy between July 1, 2011, and June 30, 2014. Multivariable risk models for major morbidity, perioperative mortality, and combined morbidity and mortality were created with the inclusion of surgical approach as a risk factor.

Results: In all, 4,321 esophagectomies were performed by 164 participating centers. The most common procedures included Ivor Lewis (32.5%), transhiatal (21.7%), minimally invasive esophagectomy, Ivor Lewis type (21.4%), and McKeown (10.0%). Sixty-nine percent of patients received induction therapy. Perioperative mortality (inpatient and 30-day) was 135 of 4,321 (3.4%). Major morbidity occurred in 1,429 patients (33.1%). Major morbidities include unexpected return to operating (15.6%), anastomotic leak (12.9%), reintubation (12.2%), initial ventilation beyond 48 hours (3.5%), pneumonia (12.2%), renal failure (2.0%), and recurrent laryngeal nerve paresis (2.0%). Statistically significant predictors of combined major morbidity or mortality included age more than 65 years, body mass index 35 kg/m(2) or greater, preoperative congestive heart failure, Zubrod score greater than 1, McKeown esophagectomy, current or former smoker, and squamous cell histology.

Conclusion: Thoracic surgeons participating in The Society of Thoracic Surgeons General Thoracic Surgery Database perform esophagectomy with low morbidity and mortality. McKeown esophagectomy is an independent predictor of combined postoperative morbidity or mortality. Revised predictors for perioperative outcome were identified to facilitate quality improvement processes and hospital comparisons.
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http://dx.doi.org/10.1016/j.athoracsur.2016.04.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016796PMC
July 2016

A Successful Institutional Strategy to Increase the Number of Therapeutic Operations Among Patients With Lung Lesions.

JAMA Surg 2016 Feb;151(2):193-4

Tennessee Valley Healthcare System, Nashville2Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.

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http://dx.doi.org/10.1001/jamasurg.2015.3253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758861PMC
February 2016