Phase II Trial Assessing Toxicity of Personalized Response-Based Radiation Treatment in Patients with Locally Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: Local failure rates after treatment for locally advanced non-small-cell lung cancer (NSCLC) remain high. Efforts to improve local control with uniform dose-escalation or dose-escalation to mid-treatment PET-avid residual disease have been limited by heightened toxicity. This trial aimed to refine response-based adaptive radiation (RT) and minimize toxicity by incorporating FDG-PET and V/Q SPECT imaging mid-treatment. METHODS: 47 patients with Stage IIA-III unresectable NSCLC were prospectively enrolled in this single-institution trial (NCT02492867). Patients received concurrent chemoradiation with personalized response-based adaptive RT over 30 fractions incorporating V/Q SPECT and FDG-PET. The first 21 fractions (46.2Gy at 2.2 Gy/fraction) were delivered to the tumor while minimizing dose to SPECT-defined functional lung. The plan was then adapted for the final 9 fractions (2.2-3.8Gy/fraction) up to a total of 80.4Gy, based on mid-treatment FDG-PET tumor response to escalate dose to residual tumor while minimizing dose to SPECT-defined functional lung. Non-progressing patients received consolidative carboplatin/paclitaxel or durvalumab. The primary endpoint of the study was ≥ grade 2 lung and esophageal toxicities. Secondary endpoints included time to local progression, tumor response, and overall survival. RESULTS: At one year post-treatment, the rates of grade 2 and grade 3 pneumonitis were 21.3% and 2.1%, respectively, with no difference in pneumonitis rates among patients who received and did not receive adjuvant durvalumab (p=0.74). While there were no grade 3 esophageal-related toxicities, 66.0% of patients experienced grade 2 esophagitis. 1- and 2-year local control rates were 94.5% (95% CI, 87.4% - 100%) and 87.5% (95% CI, 76.7% - 100%), respectively. Overall survival was 82.8% (95% CI, 72.6% -94.4%) at 1 year and 62.3% (95% CI, 49.6%-78.3%) at 2 years. CONCLUSIONS: Response-based adaptive dose-escalation accounting for tumor change and normal tissue function during treatment provided excellent local control, comparable toxicity to standard chemoradiation, and did not increase toxicity with adjuvant immunotherapy.

Longitudinal associations between exclusive, dual and polytobacco use and respiratory illness among youth.

Background: The health consequences of polytobacco use are still well not understand. We evaluated prospective associations between exclusive, dual, and polytobacco use and diagnosed bronchitis, pneumonia, or chronic cough among US youth. Methods: Data came from Waves 1-5 of the Population Assessment of Tobacco and Health Study. We categorized time-varying past 30-day tobacco use into seven categories: (1) non-current use; exclusive use of 2) cigarettes, 3) electronic nicotine delivery systems (ENDS), or 4) other combustible products (OC; pipes, hookah, and cigars); dual use of 5) ENDS + cigarettes or ENDS + OC 6) cigarettes + OC; or 7) polyuse of all three products. The outcome was incident diagnosis of bronchitis, pneumonia, or chronic cough. We conducted weighted multilevel Poisson models (person n = 17,517, 43,290 observations) to examine the longitudinal exposure-outcome relationship, adjusting for covariates: sex, age, race and ethnicity, parental education, body mass index, secondhand smoke exposure, and household use of combustible products. Results: Compared to nonuse, exclusive cigarette use (Incidence Rate Ratio (IRR) = 1.83, 95% CI 1.25-2.68), exclusive ENDS use (IRR = 1.53, 95% CI 1.08-2.15), combustible product + ENDS dual use (IRR = 1.90, 95% CI 1.18-3.04), cigarettes + OC dual use (IRR = 1.96, 95% CI 1.11-3.48), and polytobacco use (IRR = 3.06 95% CI 1.67-5.63) were associated with a higher incidence of bronchitis, pneumonia, or chronic cough. Conclusion: We found that exclusive, dual, and poly tobacco use was associated with higher incidence of bronchitis, pneumonia, or chronic cough; Moreover, the incidence rate ratio for polytobacco use was higher than the incidence rate ratio for exclusive use compared to non-current use.

Barriers to Timely Lung Cancer Care in Early Stage Non-Small Cell Lung Cancer and Impact on Patient Outcomes.

BACKGROUND: Optimal time to treatment for early-stage lung cancer is uncertain. We examined causes of delays in care for Veterans who presented with early-stage non-small cell lung cancer (NSCLC) and whether workup time was associated with increased upstaging or all-cause mortality. METHODS: We performed a retrospective analysis of Veterans referred to our facility with radiographic stage I or II NSCLC between January 2013 to December 2017, with follow-up through October 2021. Patient demographics, tumor characteristics, time intervals of care, and reasons for delays were collected. Guideline concordance (GC) was defined as treatment within 14 weeks of abnormal image. Multivariable analyses were performed to determine association between delays in care, survival, and upstaging. RESULTS: Data from 203 Veterans were analyzed. Median time between abnormal imaging to treatment was 17.7 weeks (IQR 12.7-26.6). Only 33% of Veterans received GC care. Most common patient-related delays were: intercurrent hospitalization/comorbidity (23%), no-shows (16%) and inability to reach Veteran (17%). Most common system-related delay: lack of scheduling availability (25%). Delays associated with upstaging: transportation issues, request for coordination of appointments, and unforeseen appointment changes. Rates of upstaging did not differ between GC and discordant groups (P = .6). GC care was not an independent predictor of mortality. Post-hoc, treatment within 8 weeks was associated with lower rates of upstaging (P = .05). CONCLUSION: Although GC care did not impact survival or upstaging for early-stage NSCLC, shorter timeframes may be beneficial. Modifiable delays in care exist which may be addressed at an institutional level to improve timeliness of care.

ENDS, Cigarettes, and Respiratory Illness: Longitudinal Associations Among U.S. Youth.

INTRODUCTION: ENDS use is highly prevalent among U.S. youth, and there is concern about its respiratory health effects. However, evidence from nationally representative longitudinal data is limited. METHODS: Using youth (aged 12-17 years) data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study, multilevel Poisson regression models were estimated to examine the association between ENDS use; cigarettes; and diagnosed bronchitis, pneumonia, or chronic cough. Current product use was lagged by 1 wave and categorized as (1) never/noncurrent use, (2) exclusive cigarette use, (3) exclusive ENDS use, and (4) dual ENDS/cigarette use. Multivariable models adjusted for age, sex, race and ethnicity; parental education; asthma; BMI; cannabis use; secondhand smoke exposure; and household use of combustible products. Data analysis was conducted in 2022-2023. RESULTS: A total of 7.4% of respondents were diagnosed with bronchitis, pneumonia, or chronic cough at follow-up. In the multivariable model, exclusive cigarette use (incident rate ratio=1.85, 95% CI=1.29, 2.65), exclusive ENDS use (incident rate ratio=1.49, 95% CI=1.06, 2.08), and dual use (incident rate ratio=2.70, 95% CI=1.61, 3.50) were associated with a higher risk of diagnosed bronchitis, pneumonia, or chronic cough than never/noncurrent use. CONCLUSIONS: These results suggest that ENDS and cigarettes, used exclusively or jointly, increased the risk of diagnosed bronchitis, pneumonia, or chronic cough among U.S. youth. However, dual use was associated with the highest risk. Targeted policies aimed at continuing to reduce cigarette smoking and ENDS use among youth, especially among those with dual use, are needed.

Longitudinal Association Between Exclusive and Dual Use of Cigarettes and Electronic Nicotine Delivery Systems and Asthma Among U.S. Adolescents.

PURPOSE: Electronic Nicotine Delivery Systems (ENDS) use among adolescents has increased greatly over the past decade, but its impact on chronic respiratory health conditions, like asthma, is not fully understood. METHODS: We examined data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study using discrete time hazard models to analyze the association between time-varying tobacco product use and incident diagnosed asthma among adolescents aged 12-17 years at baseline. We lagged the time-varying exposure variable by one wave and categorized respondents by current use status (1+ days in the past 30 days): never or non-current, exclusive cigarette, exclusive ENDS, and dual cigarette and ENDS use. We also controlled for sociodemographic (age, sex, race/ethnicity, parental education) and other risk factors (urban/rural setting, secondhand smoke exposure, household combustible tobacco use, body mass index). RESULTS: At baseline, over half the analytic sample (n = 9,141) was 15-17 years old (50.4%), female (50.2%), and non-Hispanic White (55.3%). Adolescents who exclusively smoked cigarettes had a statistically significant higher risk of incident diagnosed asthma at follow-up (adjusted Hazard Ratio (aHR): 1.68, 95% confidence interval (CI): 1.21-2.32) compared to those not currently using cigarettes or ENDS, but adolescents using ENDS exclusively (aHR: 1.25, 95% CI: 0.77-2.04) or in combination with cigarettes (aHR: 1.54, 95% CI: 0.92-2.57) did not. DISCUSSION: Short-term exclusive cigarette use was associated with a higher risk of incident diagnosed asthma over five years of follow-up among adolescents. We did not find conclusive evidence for an association between exclusive ENDS or dual use and incident diagnosed asthma.

Causes of and Clinical Features Associated with Death in Tobacco Cigarette Users by Lung Function Impairment.

Rationale: Cigarette smoking contributes to the risk of death through different mechanisms. Objectives: To determine how causes of and clinical features associated with death vary in tobacco cigarette users by lung function impairment. Methods: We stratified current and former tobacco cigarette users enrolled in Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) into normal spirometry, PRISm (Preserved Ratio Impaired Spirometry), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-2 COPD, and GOLD 3-4 COPD. Deaths were identified via longitudinal follow-up and Social Security Death Index search. Causes of death were adjudicated after a review of death certificates, medical records, and next-of-kin interviews. We tested associations between baseline clinical variables and all-cause mortality using multivariable Cox proportional hazards models. Measurements and Main Results: Over a 10.1-year median follow-up, 2,200 deaths occurred among 10,132 participants (age 59.5 ± 9.0 yr; 46.6% women). Death from cardiovascular disease was most frequent in PRISm (31% of deaths). Lung cancer deaths were most frequent in GOLD 1-2 (18% of deaths vs. 9-11% in other groups). Respiratory deaths outpaced competing causes of death in GOLD 3-4, particularly when BODE index ⩾7. St. George's Respiratory Questionnaire score ⩾25 was associated with higher mortality in all groups: Hazard ratio (HR), 1.48 (1.20-1.84) normal spirometry; HR, 1.40 (1.05-1.87) PRISm; HR, 1.80 (1.49-2.17) GOLD 1-2; HR, 1.65 (1.26-2.17) GOLD 3-4. History of respiratory exacerbations was associated with higher mortality in GOLD 1-2 and GOLD 3-4, quantitative emphysema in GOLD 1-2, and airway wall thickness in PRISm and GOLD 3-4. Conclusions: Leading causes of death vary by lung function impairment in tobacco cigarette users. Worse respiratory-related quality of life is associated with all-cause mortality regardless of lung function.

Longitudinal associations between exclusive, dual, and polytobacco use and asthma among US youth.

Little is known about the respiratory health effects of dual (two products) and polytobacco (three or more products) use among youth in the United States. Thus, we followed a longitudinal cohort of youth into adulthood using data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study, examining incident asthma at each follow-up (Waves 2-5). We classified past 30-day tobacco use as 1) no products (never/former use), 2) exclusive cigarettes, 3) exclusive electronic nicotine delivery systems (ENDS), 4) exclusive other combustible (OC) tobacco products (cigars, hookah, pipe), 5) dual cigarettes/OC and ENDS, 6) dual cigarettes and OCs, and 7) polytobacco use (cigarettes, OCs, and ENDS). Using discrete time survival models, we analyzed the incidence of asthma across Waves 2-5, predicted by time-varying tobacco use lagged by one wave, and adjusted for potential baseline confounders. Asthma was reported by 574 of the 9141 respondents, with an average annual incidence of 1.44% (range 0.35% to 2.02%, Waves 2-5). In adjusted models, exclusive cigarette use (HR: 1.71, 95% CI: 1.11-2.64) and dual cigarette and OC use (HR: 2.78, 95% CI: 1.65-4.70) were associated with incident asthma compared to never/former use, while exclusive ENDS use (HR: 1.50, 95% CI: 0.92-2.44) and polytobacco use (HR: 1.95, 95% CI: 0.86-4.44) were not. To conclude, youth who use cigarettes with or without OCs had higher risk of incident asthma. Further longitudinal studies on the respiratory health effects of ENDS and dual/polytobacco use are needed as products continue to evolve.

Time-varying association between cigarette and ENDS use on incident hypertension among US adults: a prospective longitudinal study.

OBJECTIVE: Electronic nicotine delivery systems (ENDS) products have emerged as the most popular alternative to combustible cigarettes. However, ENDS products contain potentially dangerous toxicants and chemical compounds, and little is known about their health effects. The aim of the present study was to examine the prospective association between cigarette and ENDS use on self-reported incident hypertension. DESIGN: Longitudinal cohort study. SETTING: Nationally representative sample of the civilian, non-institutionalised population in the USA. PARTICIPANTS: 17 539 adults aged 18 or older who participated at follow-up and had no self-reported heart condition or previous diagnosis of hypertension or high cholesterol at baseline. MEASURES: We constructed a time-varying tobacco exposure, lagged by one wave, defined as no use, exclusive established use (every day or some days) of ENDS or cigarettes, and dual use. We controlled for demographics (age, sex, race/ethnicity and household income), clinical risk factors (family history of heart attack, obesity, diabetes and binge drinking) and smoking history (cigarette pack-years). OUTCOMES: Self-reported incident hypertension diagnosis. RESULTS: The self-reported incidence of hypertension was 3.7% between wave 2 and wave 5. At baseline, 18.0% (n=5570) of respondents exclusively smoked cigarettes; 1.1% (n=336) exclusively used ENDS; and 1.7% (n=570) were dual users. In adjusted models, exclusive cigarette use was associated with an increased risk of self-reported incident hypertension compared with non-use (adjusted HR (aHR) 1.21, 95% CI 1.06 to 1.38), while exclusive ENDS use (aHR 1.00, 95% CI 0.68 to 1.47) and dual use (aHR 1.15, 95% CI 0.87 to 1.52) were not. CONCLUSIONS: We found that smoking increased the risk of self-reported hypertension, but ENDS use did not. These results highlight the importance of using prospective longitudinal data to examine the health effects of ENDS use.

Smoking Cessation, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

Although the harmful effects of smoking after a cancer diagnosis have been clearly demonstrated, many patients continue to smoke cigarettes during treatment and beyond. The NCCN Guidelines for Smoking Cessation emphasize the importance of smoking cessation in all patients with cancer and seek to establish evidence-based recommendations tailored to the unique needs and concerns of patients with cancer. The recommendations contained herein describe interventions for cessation of all combustible tobacco products (eg, cigarettes, cigars, hookah), including smokeless tobacco products. However, recommendations are based on studies of cigarette smoking. The NCCN Smoking Cessation Panel recommends that treatment plans for all patients with cancer who smoke include the following 3 tenets that should be done concurrently: (1) evidence-based motivational strategies and behavior therapy (counseling), which can be brief; (2) evidence-based pharmacotherapy; and (3) close follow-up with retreatment as needed.

Cigarettes, ENDS Use, and Chronic Obstructive Pulmonary Disease Incidence: A Prospective Longitudinal Study.

INTRODUCTION: Understanding the relationship between ENDS use and chronic obstructive pulmonary disease (COPD) and other respiratory conditions is critical. However, most previous studies have not fully adjusted for cigarette smoking history. METHODS: Using Waves 1-5 of the U.S. Population Assessment of Tobacco and Health study, the association between ENDS use and self-reported incident COPD was examined among adults aged 40+ years using discrete-time survival models. Current ENDS use was measured as a time-varying covariate, lagged by 1 wave, defined as established daily or some days of use. Multivariable models were adjusted for baseline demographics (age, sex, race/ethnicity, education), health characteristics (asthma, obesity, exposure to second-hand smoke), and smoking history (smoking status and cigarette pack years). Data were collected between 2013 and 2019, and the analysis was conducted in 2021-2022. RESULTS: Incident COPD was self-reported by 925 respondents during the 5-year follow-up. Before adjusting for other covariates, time-varying ENDS use appeared to double COPD incidence risk (hazard ratio=1.98, 95% CI=1.44, 2.74). However, ENDS use was no longer associated with COPD (adjusted hazard ratio=1.10, 95% CI=0.78, 1.57) after adjusting for current cigarette smoking and cigarette pack years. CONCLUSIONS: ENDS use did not significantly increase the risk of self-reported incident COPD over a 5-year period once current smoking status and cigarette pack years were included. Cigarette pack years, by contrast, remained associated with a net increase in COPD incidence risk. These findings highlight the importance of using prospective longitudinal data and adequately controlling for cigarette smoking history to assess the independent health effects of ENDS.

Temporal Trends and Variation in Bronchoscopy Use for Acute Respiratory Failure in the United States.

BACKGROUND: National data on bronchoscopy for the evaluation of acute respiratory failure are lacking, and the limited available data suggest wide variation in use. RESEARCH QUESTION: How commonly is bronchoscopy performed among hospitalizations with acute respiratory failure? How has use changed over time and across hospitals? STUDY DESIGN AND METHODS: This was an observational cohort study of adult hospitalizations (2012-2018) treated with invasive mechanical ventilation (IMV) using the National Inpatient Sample, which represents 97% of all hospitalizations in the United States. We measured the proportion of hospitalizations treated with IMV who underwent bronchoscopy and assessed trends in bronchoscopy use over time. Multilevel linear regression models were used to quantify hospital-level variation, adjusting for differences in patient and hospital characteristics. RESULTS: We identified 6,101,070 IMV-treated hospitalizations (2012-2018), of whom 609,405 underwent bronchoscopy; among hospitalizations receiving bronchoscopy, mean age was 61 years, 41.8% were women, and in-hospital mortality was 30.8%. The percentage of IMV-treated hospitalizations receiving bronchoscopy increased from 9.5% (95% CI, 9.1%-9.9%) in 2012 to 10.8% (95% CI, 10.4%-11.2%) in 2018 (P < .001 for difference). In 2018, bronchoscopy use varied from 0% to 57.1% among 1,787 hospitals, and in multilevel models adjusted for patient and hospital characteristics, 16.0% of the variation was explained at the hospital level. The median OR was 2.13 (95% CI, 2.05-2.21), indicating 113% increased odds of receiving bronchoscopy if moving from a lower-use to a higher-use hospital. INTERPRETATION: Bronchoscopy use among hospitalizations treated with IMV has increased over time. The large variation in use of bronchoscopy across hospitals suggests potentially unwarranted practice variation and need for further studies to clarify which patients benefit from bronchoscopy.

Longitudinal Associations Between Exclusive and Dual Use of Electronic Nicotine Delivery Systems and Cigarettes and Self-Reported Incident Diagnosed Cardiovascular Disease Among Adults.

INTRODUCTION: The cardiovascular health effects of electronic nicotine delivery systems (ENDS) use are not well characterized, making it difficult to assess ENDS as a potential harm reduction tool for adults who use cigarettes. AIMS AND METHODS: Using waves 1-5 of the Population Assessment of Tobacco and Health Study (2013-2019), we analyzed the risk of self-reported incident diagnosed myocardial infarction (MI; 280 incident cases) and stroke (186 incident cases) associated with ENDS and/or cigarette use among adults aged 40 + using discrete time survival models. We employed a time-varying exposure lagged by one wave, defined as exclusive or dual established use of ENDS and/or cigarettes every day or some days, and controlled for demographics, clinical factors, and past smoking history. RESULTS: The analytic samples (MI = 11 031; stroke = 11 076) were predominantly female and non-Hispanic White with a mean age of 58 years. At baseline, 14.2% of respondents exclusively smoked cigarettes, 0.6% exclusively used ENDS, and 1.0% used both products. Incident MI and stroke were rare during follow-up (< 1% at each wave). Compared to no cigarette or ENDS use, exclusive cigarette use increased the risk of MI (aHR 1.99, 95% CI = 1.40-2.84) and stroke (aHR 2.26, 95% CI = 1.51-3.39), while exclusive ENDS use (MI: aHR 0.61, 95% CI = 0.12-3.04; stroke: aHR 1.74, 95% CI = 0.55-5.49) and dual use (MI: aHR 1.84, 95% CI = 0.64-5.30; stroke: aHR 1.12, 95% CI = 0.33-3.79) were not significantly associated with the risk of either outcome. CONCLUSIONS: Compared to non-use, exclusive cigarette use was associated with an increased risk of self-reported incident diagnosed cardiovascular disease over a 5-year period, while ENDS use was not associated with a statistically significant increase in the outcomes. IMPLICATIONS: Existing literature on the health effects of ENDS use has important limitations, including potential reverse causation and improper control for cigarette smoking. We accounted for these issues by using a prospective design and adjusting for current and former smoking status and cigarette pack-years. In this context, we did not find that ENDS use was associated with a statistically significant increase in self-reported incident diagnosed myocardial infarction or stroke over a 5-year period. While more studies are needed, this analysis provides an important foundation and key methodological considerations for future research on the health effects of ENDS use.

Prevalence and consequences of non-adherence to an evidence-based approach for incidental pulmonary nodules.

IMPORTANCE: Distinguishing benign from malignant pulmonary nodules is challenging. Evidence-based guidelines exist, but their impact on patient-centered outcomes is unknown. OBJECTIVE: To understand if the evaluation of incidental pulmonary nodules that follows an evidence-based management strategy is associated with fewer invasive procedures for benign lesions and/or fewer delays in cancer diagnosis. DESIGN: Retrospective cohort study. SETTING: Large academic medical center. PARTICIPANTS: Adults (≥18 years age) with an incidental pulmonary nodule discovered between January 2012 and December 2014. Patients with calcified nodules, prior nodules, prior diagnosis of cancer, high suspicion for pulmonary metastasis, or limited life expectancy were excluded. EXPOSURE: Nodule management strategy (pre-specified based on evidence-based practices). OUTCOME: Composite of any invasive procedure for a benign nodule or delay in diagnosis in patients with cancer (>3 month delay once probability of cancer was >15%). RESULTS: Of 314 patients that met inclusion criteria, median age was 61, 46.5% were men, and 66.5% had current or former tobacco use. The mean nodule size was 10.3 mm, mean probability of cancer was 11.8%, and 14.3% of nodules were malignant. Evaluation followed an evidence-based strategy in 245 patients (78.0%), and deviated in 69 patients (22%). The composite outcome occurred in 26 (8.3%) patients. Among patients whose nodule evaluation was concordant with an evidence-based evaluation, 6.1% (15/245) experienced the composite outcome versus 15.9% (11/69) of patients with an evaluation that deviated from evidence-based recommendations (P<0.01). CONCLUSIONS AND RELEVANCE: At a large academic medical center, more than 1 in 5 patients with an incidental pulmonary nodule underwent evaluation that deviated from evidence-based practice recommendations. Nodule evaluation that deviated from an evidence-based strategy was associated with biopsy of benign lesions and delays in cancer diagnosis, suggesting a need to improve guideline uptake.

NAVIGATE 24-Month Results: Electromagnetic Navigation Bronchoscopy for Pulmonary Lesions at 37 Centers in Europe and the United States.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive, image-guided approach to access lung lesions for biopsy or localization for treatment. However, no studies have reported prospective 24-month follow-up from a large, multinational, generalizable cohort. This study evaluated ENB safety, diagnostic yield, and usage patterns in an unrestricted, real-world observational design. METHODS: The NAVIGATE single-arm, pragmatic cohort study (NCT02410837) enrolled subjects at 37 academic and community sites in seven countries with prospective 24-month follow-up. Subjects underwent ENB using the superDimension navigation system versions 6.3 to 7.1. The prespecified primary end point was procedure-related pneumothorax requiring intervention or hospitalization. RESULTS: A total of 1388 subjects were enrolled for lung lesion biopsy (1329; 95.7%), fiducial marker placement (272; 19.6%), dye marking (23; 1.7%), or lymph node biopsy (36; 2.6%). Concurrent endobronchial ultrasound-guided staging occurred in 456 subjects. General anesthesia (78.2% overall, 56.6% Europe, 81.4% United States), radial endobronchial ultrasound (50.6%, 4.0%, 57.4%), fluoroscopy (85.0%, 41.7%, 91.0%), and rapid on-site evaluation use (61.7%, 17.3%, 68.5%) differed between regions. Pneumothorax and bronchopulmonary hemorrhage occurred in 4.7% and 2.7% of subjects, respectively (3.2% [primary end point] and 1.7% requiring intervention or hospitalization). Respiratory failure occurred in 0.6%. The diagnostic yield was 67.8% (range: 61.9%-70.7%; 55.2% Europe, 69.8% United States). Sensitivity for malignancy was 62.6%. Lung cancer clinical stage was I to II in 64.7% (55.3% Europe, 65.8% United States). CONCLUSIONS: Despite a heterogeneous cohort and regional differences in procedural techniques, ENB demonstrates low complications and a 67.8% diagnostic yield while allowing biopsy, staging, fiducial placement, and dye marking in a single procedure.

Management of Stage III Non-Small-Cell Lung Cancer: ASCO Guideline.

PURPOSE: To provide evidence-based recommendations to practicing clinicians on management of patients with stage III non-small-cell lung cancer (NSCLC). METHODS: An Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary oncology, community oncology, research methodology, and advocacy experts was convened to conduct a literature search, which included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2021. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 127 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS: Evidence-based recommendations were developed to address evaluation and staging workup of patients with suspected stage III NSCLC, surgical management, neoadjuvant and adjuvant approaches, and management of patients with unresectable stage III NSCLC.Additional information is available at www.asco.org/thoracic-cancer-guidelines.