Uptake of Lung Cancer Screening CT After a Provider Order for Screening in the PROSPR-Lung Consortium.

BACKGROUND: Uptake of lung cancer screening (LCS) has been slow with less than 20% of eligible people who currently or formerly smoked reported to have undergone a screening CT. OBJECTIVE: To determine individual-, health system-, and neighborhood-level factors associated with LCS uptake after a provider order for screening. DESIGN AND SUBJECTS: We conducted an observational cohort study of screening-eligible patients within the Population-based Research to Optimize the Screening Process (PROSPR)-Lung Consortium who received a radiology referral/order for a baseline low-dose screening CT (LDCT) from a healthcare provider between January 1, 2015, and June 30, 2019. MAIN MEASURES: The primary outcome is screening uptake, defined as LCS-LDCT completion within 90 days of the screening order date. KEY RESULTS: During the study period, 18,294 patients received their first order for LCS-LDCT. Orders more than doubled from the beginning to the end of the study period. Overall, 60% of patients completed screening after receiving their first LCS-LDCT order. Across health systems, uptake varied from 41 to 87%. In both univariate and multivariable analyses, older age, male sex, former smoking status, COPD, and receiving care in a centralized LCS program were positively associated with completing LCS-LDCT. Unknown insurance status, other or unknown race, and lower neighborhood socioeconomic status, as measured by the Yost Index, were negatively associated with screening uptake. CONCLUSIONS: Overall, 40% of patients referred for LCS did not complete a LDCT within 90 days, highlighting a substantial gap in the lung screening care pathway, particularly in decentralized screening programs.

Application of bronchoscopy in the diagnosis and treatment of peripheral pulmonary lesions in China: a national cross-sectional study.

Background: Bronchoscopy has gradually become valuable armamentarium in evaluating and applying endoscopic therapy to peripheral pulmonary lesions (PPLs) around the world. We aimed to make a comprehensive understanding of the application of bronchoscopy in the diagnosis and treatment of PPLs in China. Methods: A cross-sectional survey was carried out in China between January 2022 and March 2022. The survey was in the form of an online questionnaire which was filled in with real-time data by the respondents. Results: A total of 347 doctors from 284 tertiary hospitals (81.8%) and 63 secondary general hospitals (18.2%) were included in the data analysis. More than half of the surveyed doctors (55.0%) had independently performed respiratory endoscopy for 5-15 years. Higher proportions of hospitals with a fixed nursing team, anesthesiologists and rapid on-site evaluation (ROSE) during bronchoscopic procedures were performed in tertiary hospitals than those in secondary general hospitals (P<0.001 each). There were 316 hospitals (91.7%) eligible for performing biopsies of PPLs less than 30mm, while more than 300 PPLs biopsies were performed in only 78 hospitals (24.7%) per year. Radial probe endobronchial ultrasound (r-EBUS) (50.3%) was the commonest type of technique used in the guidance of a bronchoscope to PPLs, followed by navigational bronchoscopy (30.3%) and cone beam CT (CBCT) (17.0%). Although two thirds of the surveyed hospitals had at least one bronchoscopic guidance devices, the actual utilization of these devices was not high due to high capital costs and absence of training. To note, more diagnostic procedures and allocated devices were concentrated in the southeast region and coastal cities. Furthermore, therapeutic bronchoscopic interventions for peripheral lung cancer and/or high-risk PPLs could be performed in 124 (35.7%) of the 347 involved hospitals. Conclusions: Bronchoscopy for the diagnosis of PPLs has been carried out in most hospitals in China and yields in different hospitals and regions varied greatly. To date, only a few hospitals in China can develop therapeutic bronchoscopy for PPLs.

Clinical Outcome in Patients With Early-Stage Small Cell Lung Cancer Treated With Surgery or Radiation in the Absence of Prophylactic Cranial Irradiation: A Single-Center Retrospective Study.

Purpose: As screening chest computed tomography for patients at high risk for cancer has become more widely accepted, increasing numbers of patients with early-stage small cell lung cancer (SCLC) are being diagnosed. Although surgery is an accepted option for patients with early-stage SCLC, for patients who decline or cannot undergo surgery, stereotactic body radiation treatment (SBRT) is an alternative. Although prophylactic cranial irradiation (PCI) improves survival in patients with limited-stage SCLC, PCI for early-stage SCLC (stage T1-T2) has not been explored. This study defines survival and recurrence patterns in patients with early-stage SCLC who were treated with surgery or SBRT in the absence of PCI. Methods and Materials: In this single-institution retrospective study, 14 patients diagnosed with early-stage SCLC (stage T1-T2) between July 2015 and May 2021 at a single tertiary care hospital were treated with SBRT or surgery with no PCI. Primary outcomes were locoregional cancer recurrence, distant recurrence, recurrence-free survival, and overall survival. The secondary outcome was development of brain metastasis. Analyses included Cox regression, Kaplan-Meier survival, and log-rank tests. Results: A total of 14 patients (5 women and 9 men) were included in the study: 9 with stage T1 and 5 with stage T2 SCLC. Six patients (43%) received SBRT and 8 (57%) had surgical treatment. All patients except 1 received adjuvant chemotherapy. Median follow-up was 14.3 months (range, 2.4-64.4 months), and the median age at diagnosis was 71.5 years (range, 54-81 years). Cox regression and log-rank tests showed no significant differences in any outcomes between the surgery and SBRT groups, and no patients developed brain metastases during the study period. Conclusions: Data are lacking regarding the benefit of PCI in early-stage SCLC. Although the sample size in this study was too small to draw any conclusions, the findings add to the ongoing dialogue regarding the importance of PCI in this patient population. No difference was identified in survival and cancer recurrence in patients who received either surgery or SBRT in the absence of PCI.

Stage Migration and Lung Cancer Incidence After Initiation of Low-Dose Computed Tomography Screening.

INTRODUCTION: Despite evidence from clinical trials of favorable shifts in cancer stage and improvements in lung cancer-specific mortality, the effectiveness of lung cancer screening (LCS) in clinical practice has not been clearly revealed. METHODS: We performed a multicenter cohort study of patients diagnosed with a primary lung cancer between January 1, 2014, and September 30, 2019, at one of four U.S. health care systems. The primary outcome variables were cancer stage distribution and annual age-adjusted lung cancer incidence. The primary exposure variable was receipt of at least one low-dose computed tomography for LCS before cancer diagnosis. RESULTS: A total of 3678 individuals were diagnosed with an incident lung cancer during the study period; 404 (11%) of these patients were diagnosed after initiation of LCS. As screening volume increased, the proportion of patients diagnosed with lung cancer after LCS initiation also rose from 0% in the first quartile of 2014 to 20% in the third quartile of 2019. LCS did not result in a significant change in the overall incidence of lung cancer (average annual percentage change [AAPC]: -0.8 [95% confidence interval (CI): -4.7 to 3.2]) between 2014 and 2018. Stage-specific incidence rates increased for stage I cancer (AAPC = 8.0 [95% CI: 0.8-15.7]) and declined for stage IV disease (AAPC = -6.0 [95% CI: -11.2 to -0.5]). CONCLUSIONS: Implementation of LCS at four diverse health care systems has resulted in a favorable shift to a higher incidence of stage I cancer with an associated decline in stage IV disease. Overall lung cancer incidence did not increase, suggesting a limited impact of overdiagnosis.

Artificial Intelligence Tool for Assessment of Indeterminate Pulmonary Nodules Detected with CT.

Background Limited data are available regarding whether computer-aided diagnosis (CAD) improves assessment of malignancy risk in indeterminate pulmonary nodules (IPNs). Purpose To evaluate the effect of an artificial intelligence-based CAD tool on clinician IPN diagnostic performance and agreement for both malignancy risk categories and management recommendations. Materials and Methods This was a retrospective multireader multicase study performed in June and July 2020 on chest CT studies of IPNs. Readers used only CT imaging data and provided an estimate of malignancy risk and a management recommendation for each case without and with CAD. The effect of CAD on average reader diagnostic performance was assessed using the Obuchowski-Rockette and Dorfman-Berbaum-Metz method to calculate estimates of area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Multirater Fleiss κ statistics were used to measure interobserver agreement for malignancy risk and management recommendations. Results A total of 300 chest CT scans of IPNs with maximal diameters of 5-30 mm (50.0% malignant) were reviewed by 12 readers (six radiologists, six pulmonologists) (patient median age, 65 years; IQR, 59-71 years; 164 [55%] men). Readers' average AUC improved from 0.82 to 0.89 with CAD (P < .001). At malignancy risk thresholds of 5% and 65%, use of CAD improved average sensitivity from 94.1% to 97.9% (P = .01) and from 52.6% to 63.1% (P < .001), respectively. Average reader specificity improved from 37.4% to 42.3% (P = .03) and from 87.3% to 89.9% (P = .05), respectively. Reader interobserver agreement improved with CAD for both the less than 5% (Fleiss κ, 0.50 vs 0.71; P < .001) and more than 65% (Fleiss κ, 0.54 vs 0.71; P < .001) malignancy risk categories. Overall reader interobserver agreement for management recommendation categories (no action, CT surveillance, diagnostic procedure) also improved with CAD (Fleiss κ, 0.44 vs 0.52; P = .001). Conclusion Use of computer-aided diagnosis improved estimation of indeterminate pulmonary nodule malignancy risk on chest CT scans and improved interobserver agreement for both risk stratification and management recommendations. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Yanagawa in this issue.

Racial Disparities in Adherence to Annual Lung Cancer Screening and Recommended Follow-Up Care: A Multicenter Cohort Study.

Rationale: Black patients receive recommended lung cancer screening (LCS) follow-up care less frequently than White patients, but it is unknown if this racial disparity persists across both decentralized and centralized LCS programs. Objectives: To determine adherence to American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS) recommendations among individuals undergoing LCS at either decentralized or centralized programs and to evaluate the association of race with LCS adherence. Methods: We performed a multicenter retrospective cohort study of patients receiving LCS at five heterogeneous U.S. healthcare systems. We calculated adherence to annual LCS among patients with a negative baseline screen (Lung-RADS 1 or 2) and recommended follow-up care among those with a positive baseline screen (Lung-RADS 3, 4A, 4B, or 4X) stratified by type of LCS program and evaluated the association between race and adherence using multivariable modified Poisson regression. Results: Of the 6,134 total individuals receiving LCS, 5,142 (83.8%) had negative baseline screens, and 992 (16.2%) had positive baseline screens. Adherence to both annual LCS (34.8% vs. 76.1%; P < 0.001) and recommended follow-up care (63.9% vs. 74.6%; P < 0.001) was lower at decentralized compared with centralized programs. Among individuals with negative baseline screens, a racial disparity in adherence was observed only at decentralized screening programs (interaction term, P < 0.001). At decentralized programs, Black race was associated with 27% reduced adherence to annual LCS (adjusted relative risk [aRR], 0.73; 95% confidence interval [CI], 0.63-0.84), whereas at centralized programs, no effect by race was observed (aRR, 0.98; 95% CI, 0.91-1.05). In contrast, among those with positive baseline screens, there was no significant difference by race for adherence to recommended follow-up care by type of LCS program (decentralized aRR, 0.95; 95% CI, 0.81-1.11; centralized aRR, 0.81; 95% CI, 0.71-0.93; interaction term, P = 0.176). Conclusions: In this large multicenter study of individuals screened for lung cancer, adherence to both annual LCS and recommended follow-up care was greater at centralized screening programs. Black patients were less likely to receive annual LCS than White patients at decentralized compared with centralized LCS programs. Our results highlight the need for further study of healthcare system-level mechanisms to optimize longitudinal LCS care.

Comparing Smoking Cessation Interventions among Underserved Patients Referred for Lung Cancer Screening: A Pragmatic Trial Protocol.

Smoking burdens are greatest among underserved patients. Lung cancer screening (LCS) reduces mortality among individuals at risk for smoking-associated lung cancer. Although LCS programs must offer smoking cessation support, the interventions that best promote cessation among underserved patients in this setting are unknown. This stakeholder-engaged, pragmatic randomized clinical trial will compare the effectiveness of four interventions promoting smoking cessation among underserved patients referred for LCS. By using an additive study design, all four arms provide standard "ask-advise-refer" care. Arm 2 adds free or subsidized pharmacologic cessation aids, arm 3 adds financial incentives up to $600 for cessation, and arm 4 adds a mobile device-delivered episodic future thinking tool to promote attention to long-term health goals. We hypothesize that smoking abstinence rates will be higher with the addition of each intervention when compared with arm 1. We will enroll 3,200 adults with LCS orders at four U.S. health systems. Eligible patients include those who smoke at least one cigarette daily and self-identify as a member of an underserved group (i.e., is Black or Latinx, is a rural resident, completed a high school education or less, and/or has a household income <200% of the federal poverty line). The primary outcome is biochemically confirmed smoking abstinence sustained through 6 months. Secondary outcomes include abstinence sustained through 12 months, other smoking-related clinical outcomes, and patient-reported outcomes. This pragmatic randomized clinical trial will identify the most effective smoking cessation strategies that LCS programs can implement to reduce smoking burdens affecting underserved populations. Clinical trial registered with clinicaltrials.gov (NCT04798664). Date of registration: March 12, 2021. Date of trial launch: May 17, 2021.

Ion: Technology and Techniques for Shape-sensing Robotic-assisted Bronchoscopy.

PURPOSE: This report describes the Ion Endoluminal System (Intuitive Surgical, Inc, Sunnyvale, CA) and practices for safe and effective use in patients with small peripheral pulmonary nodules (PPNs). DESCRIPTION: This shape-sensing robotic-assisted bronchoscopy system allows airway visualization and navigation to reach and biopsy small PPNs through a stable platform. The system provides 3-dimensional mapping and visualization of the airways, a flexible and fully articulating 3.5-mm (outer diameter) catheter, a peripheral vision probe, and system-specific biopsy needles. EVALUATION: The Ion Endoluminal System was evaluated in an ongoing prospective, multicenter trial including 241 patients with 270 PPNs (largest mean cardinal measurement, 18.8 ± 6.5 mm). Mean time to register and navigate decreased from 10 minutes in the first 10 cases to 7 minutes in the subsequent cases. Asymptomatic pneumothorax occurred in 8 patients (3.3%), 1 (0.4%) with pigtail catheter placement. Two patients (0.8%) experienced airway bleeding; both cases of bleeding resolved within 5 minutes of tamponade. CONCLUSIONS: The Ion Endoluminal System's unique shape-sensing technology can be leveraged to facilitate localization and sampling of PPNs and potentially improve diagnostic accuracy.

An Analysis of Clinical Toxic Effects and Quality of Life as a Function of Radiation Dose and Volume After Lung Stereotactic Body Radiation Therapy.

PURPOSE: To analyze clinical toxicity and quality-of-life (QOL) outcomes among patients with stage I non-small cell lung cancer (NSCLC) after stereotactic body radiation therapy (SBRT) as a function of radiation dose and volume parameters. METHODS AND MATERIALS: In this institutional review board-approved study, 55 patients with stage I NSCLC who received SBRT (12 Gy × 4) and completed QOL forms were analyzed. Clinical symptoms and QOL outcomes were measured at baseline and at 3, 6, 12, 18, 24, and 36 months after SBRT. Clinical toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0. Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Lung-Trial Outcome Index (FACT-L-TOI) instrument. Dosimetric parameters including the mean lung radiation dose and the volume of normal lung receiving greater than 5, 10, 13, or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student t tests and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxic effects. The Kaplan-Meier method was used to estimate rates of local control (LC), disease-free survival (DFS), and overall survival (OS). RESULTS: With a median follow-up of 24 months, the 3-year LC, DFS, and OS were 93%, 65%, and 84%, respectively, with a 5.5% rate of grade-3 toxic effects and no grade 4 or 5 toxic effects. Clinically meaningful declines in patient-reported QOL (FACT-L-TOI, lung cancer subscale, physical well-being, and/or functional well-being) posttreatment significantly correlated with increased dosimetric parameters such as V10, V13, and V20. CONCLUSION: Although lung SBRT was associated with excellent LC and minimal clinical toxic effects for early-stage NSCLC, clinically meaningful declines in QOL were significantly correlated with increasing lung dose and volume parameters.

Shape-sensing robotic-assisted bronchoscopy for pulmonary nodules: initial multicenter experience using the Ion™ Endoluminal System.

BACKGROUND: Traditional bronchoscopy provides limited approach to peripheral nodules. Shape-sensing robotic-assisted bronchoscopy (SSRAB, Ion™ Endoluminal System) is a new tool for minimally invasive peripheral nodule biopsy. We sought to answer the research question: Does SSRAB facilitate sampling of pulmonary nodules during bronchoscopists' initial experience? METHODS: The lead-in stage of a multicenter, single-arm, prospective evaluation of the Ion Endoluminal System (PRECIsE) is described. Enrolled subjects ≥ 18 years old had recent computed tomography evidence of one or more solid or semi-solid pulmonary nodules ≥ 1.0 to ≤ 3.5 cm in greatest dimension and in any part of the lung. Subjects were followed at 10- and 30-days post-procedure. This stage provided investigators and staff their first human experience with the SSRAB system; safety and procedure outcomes were analyzed descriptively. Neither diagnostic yield nor sensitivity for malignancy were assessed in this stage. Categorical variables are summarized by percentage; continuous variables are summarized by median/interquartile range (IQR). RESULTS: Sixty subjects were enrolled across 6 hospitals; 67 nodules were targeted for biopsy. Median axial, coronal and sagittal diameters were < 18 mm with a largest cardinal diameter of 20.0 mm. Most nodules were extraluminal and distance from the outer edge of the nodule to the pleura or nearest fissure was 4.0 mm (IQR: 0.0, 15.0). Median bronchial generation count to the target location was 7.0 (IQR: 6.0, 8.0). Procedure duration (catheter-in to catheter-out) was 66.5 min (IQR: 50.0, 85.5). Distance from the catheter tip to the closest edge of the virtual nodule was 7.0 mm (IQR: 2.0, 12.0). Biopsy completion was 97.0%. No pneumothorax or airway bleeding of any grade was reported. CONCLUSIONS: Bronchoscopists leveraged the Ion SSRAB's functionality to drive the catheter safely in close proximity of the virtual target and to obtain biopsies. This initial, multicenter experience is encouraging, suggesting that SSRAB may play a role in the management of pulmonary nodules. Clinical Trial Registration identifier and date NCT03893539; 28/03/2019.

Predicting Lymph Node Metastasis in Non-small Cell Lung Cancer: Prospective External and Temporal Validation of the HAL and HOMER Models.

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers? STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. RESULTS: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. INTERPRETATION: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.

Understanding the patient journey to diagnosis of lung cancer.

OBJECTIVE: This research describes the clinical pathway and characteristics of two cohorts of patients. The first cohort consists of patients with a confirmed diagnosis of lung cancer while the second consists of patients with a solitary pulmonary nodule (SPN) and no evidence of lung cancer. Linked data from an electronic medical record and the Louisiana Tumor Registry were used in this investigation. MATERIALS AND METHODS: REACHnet is one of 9 clinical research networks (CRNs) in PCORnet®, the National Patient-Centered Clinical Research Network and includes electronic health records for over 8 million patients from multiple partner health systems. Data from Ochsner Health System and Tulane Medical Center were linked to Louisiana Tumor Registry (LTR), a statewide population-based cancer registry, for analysis of patient's clinical pathways between July 2013 and 2017. Patient characteristics and health services utilization rates by cancer stage were reported as frequency distributions. The Kaplan-Meier product limit method was used to estimate the time from index date to diagnosis by stage in lung cancer cohort. RESULTS: A total of 30,559 potentially eligible patients were identified and 2929 (9.58%) had primary lung cancer. Of these, 1496 (51.1%) were documented in LTR and their clinical pathway to diagnosis was further studied. Time to diagnosis varied significantly by cancer stage. A total of 24,140 patients with an SPN were identified in REACHnet and 15,978 (66.6%) had documented follow up care for 1 year. 1612 (10%) had no evidence of any work up for their SPN. The remaining 14,366 had some evidence of follow up, primarily office visits and additional chest imaging. CONCLUSION: In both cohorts multiple biopsies were evident in the clinical pathway. Despite clinical workup, 70% of patients in the lung cancer cohort had stage III or IV disease. In the SPN cohort, only 66% were identified as receiving a diagnostic work-up.

Costs of Biopsy and Complications in Patients with Lung Cancer.

PURPOSE: To describe the distribution of diagnostic procedures, rates of complications, and total cost of biopsies for patients with lung cancer. PATIENTS AND METHODS: Observational study using data from IBM Marketscan® Databases for continuously insured adult patients with a primary lung cancer diagnosis and treatment between July 2013 and June 2017. Costs of lung cancer diagnosis covered 6 months prior to index biopsy through treatment. Costs of chest CT scans, biopsy, and post-procedural complications were estimated from total payments. Costs of biopsies incidental to inpatient admissions were estimated by comparable outpatient biopsies. RESULTS: The database included 22,870 patients who had a total of 37,160 biopsies, of which 16,009 (43.1%) were percutaneous, 14,997 (40.4%) bronchoscopic, 4072 (11.0%) surgical and 2082 (5.6%) mediastinoscopic. Multiple biopsies were performed on 41.9% of patients. The most common complications among patients receiving only one type of biopsy were pneumothorax (1304 patients, 8.4%), bleeding (744 patients, 4.8%) and intubation (400 patients, 2.6%). However, most complications did not require interventions that would add to costs. Median total costs were highest for inpatient surgical biopsies ($29,988) and lowest for outpatient percutaneous biopsies ($1028). Repeat biopsies of the same type increased costs by 40-80%. Complications account for 13% of total costs. CONCLUSION: Costs of biopsies to confirm lung cancer diagnosis vary substantially by type of biopsy and setting. Multiple biopsies, inpatient procedures and complications result in higher costs.

Safety and effectiveness of bronchial thermoplasty after 10 years in patients with persistent asthma (BT10+): a follow-up of three randomised controlled trials.

BACKGROUND: Bronchial thermoplasty is an endoscopic treatment for uncontrolled asthma. Previous randomised clinical trials have shown that bronchial thermoplasty reduces severe exacerbations in people with asthma. However, the long-term efficacy and safety of bronchial thermoplasty beyond 5 years is unknown. The BT10+ study aimed to investigate the efficacy and safety of bronchial thermoplasty after 10 or more years of follow-up. METHODS: BT10+ was an international, multicentre, follow-up study of participants who were previously enrolled in the AIR, RISA, and AIR2 trials and who had 10 or more years of follow-up since bronchial thermoplasty treatment. Data on patient demographics, quality of life, lung function, CT scans (AIR2 participants only), severe exacerbations, and health-care use during the previous year were collected at the BT10+ 10-year outcomes study visit. The primary effectiveness endpoint was durability of the thermoplasty treatment effect, determined by comparing the proportion of participants who had severe exacerbations during the first and fifth years after bronchial thermoplasty treatment with the proportion of participants who had severe exacerbations during the 12-month period before the BT10+ visit. The primary safety endpoint was the absence of clinically significant post-treatment respiratory image changes after bronchial thermoplasty, defined as bronchiectasis or bronchial stenosis as confirmed by pulmonary volumetric high-resolution CT scan at the BT10+ visit (AIR2 participants only). All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03243292. The last patient was enrolled on Dec 11, 2018. The last patient completed follow-up on Jan 10, 2019. FINDINGS: The BT10+ study enrolled 192 (45%) of the 429 participants who were enrolled in the AIR, RISA, and AIR2 trials. The BT10+ participants comprised 136 who received bronchial thermoplasty (52% of the 260 participants who received bronchial thermoplasty in the original trials), and 56 sham or control participants (33% of 169 from the original trials). 18 (32%) sham or control participants received bronchial thermoplasty after the previous trials concluded. The participants included in BT10+ were followed for 10·8-15·6 years (median 12·1 years) post-treatment. Baseline characteristics were similar between participants enrolled in BT10+ and those not enrolled. Participants treated with bronchial thermoplasty had similar proportions of severe exacerbations at the BT10+ visit (34 [25%] of 136 participants) compared with 1 year (33 [24%] of 135 participants; difference 0·6%, 95% CI -9·7 to 10·8) and 5 years (28 [22%] of 130 participants; difference 3·5%, -6·7% to 13·6) after treatment. Quality of life measurements and spirometry were similar between year 1, year 5, and the BT10+ visit. At the BT10+ study visit, pulmonary high-resolution CT scans from AIR2 participants treated with bronchial thermoplasty showed that 13 (13%) of 97 participants had bronchiectasis. When compared with baseline high-resolution CT scans, six (7%) of 89 participants treated with bronchial thermoplasty who did not have bronchiectasis at baseline had developed bronchiectasis after treatment (5 classified as mild, 1 classified as moderate). Participants treated with bronchial thermoplasty after the original study and participants in the sham or control group also had reductions in severe exacerbations at the BT10+ visit compared with baseline. INTERPRETATION: Our findings suggest that efficacy of bronchial thermoplasty is sustained for 10 years or more, with an acceptable safety profile. Therefore, bronchial thermoplasty is a long-acting therapeutic option for patients with asthma that remains uncontrolled despite optimised medical treatment. FUNDING: Boston Scientific.

Robotic Bronchoscopy for Peripheral Pulmonary Lesions: A Multicenter Pilot and Feasibility Study (BENEFIT).

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects. RESEARCH QUESTION: What is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs? STUDY DESIGN AND METHODS: This was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 cm in size. The primary end points were successful lesion localization with the use of radial probe endobronchial ultrasound (R-EBUS) imaging and incidence of procedure related adverse events. Robotic bronchoscopy was performed in patients with the use of direct visualization, electromagnetic navigation, and fluoroscopy. After the use of R-EBUS imaging, transbronchial needle aspiration was performed. Rapid on-site evaluation (ROSE) was used on all cases. Transbronchial needle aspiration alone was sufficient when ROSE was diagnostic; when ROSE was not diagnostic, transbronchial biopsy was performed with the use of the robotic platform, followed by conventional guided bronchoscopic approaches at the discretion of the investigator. RESULTS: Fifty-five patients were enrolled at five centers. One patient withdrew consent, which left 54 patients for data analysis. Median lesion size was 23 mm (interquartile range, 15 to 29 mm). R-EBUS images were available in 53 of 54 cases. Lesion localization was successful in 51 of 53 patients (96.2%). Pneumothorax was reported in two of 54 of the cases (3.7%); tube thoracostomy was required in one of the cases (1.9 %). No additional adverse events occurred. INTERPRETATION: This is the first, prospective, multicenter study of robotic bronchoscopy in patients with PPLs. Successful lesion localization was achieved in 96.2% of cases, with an adverse event rate comparable with conventional bronchoscopic procedures. Additional large prospective studies are warranted to evaluate procedure characteristics, such as diagnostic yield. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03727425; URL: www.clinicaltrials.gov.

Biopsy frequency and complications among lung cancer patients in the United States.

OBJECTIVE: This study aimed to describe the frequency and distribution of biopsy procedures for patients diagnosed and treated for primary lung cancer. STUDY DESIGN: Retrospective cohort study within an administrative database. MATERIALS & METHODS: This observational study used data from the IBM MarketScan® Databases between 2013 and 2015. RESULTS: The total number of lung biopsies performed among eligible subjects was 32,814; an average of 1.7 biopsies per patient. Bronchoscopy and percutaneous approaches accounted for 95% of all procedures. Complication rates by procedure are remarkably similar irrespective of biopsy frequency. CONCLUSION: Nearly half (46%) of patients in this population experienced multiple biopsies prior to diagnosis. Further, biopsy choice or sequence in patients receiving multiple procedures was unpredictable.

Correlation of normal lung density changes with dose after stereotactic body radiotherapy (SBRT) for early stage lung cancer.

BACKGROUND AND PURPOSE: To investigate the correlation between normal lung CT density changes with dose accuracy and outcome after stereotactic body radiation therapy (SBRT) for patients with early stage non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Thirty-one patients (with a total of 33 lesions) with non-small cell lung cancer were selected out of 270 patients treated with SBRT at a single institution between 2003 and 2009. Out of these 31 patients, 10 patients had developed radiation pneumonitis (RP). Dose distributions originally planned using a 1-D pencil beam-based dose algorithm were retrospectively recomputed using different algorithms. Prescription dose was 48 Gy in 4 fractions in most patients. Planning CT images were rigidly registered to follow-up CT datasets at 3-9 months after treatment. Corresponding dose distributions were mapped from planning to follow-up CT images. Hounsfield Unit (HU) changes in lung density in individual, 5 Gy, dose bins from 5 to 45 Gy were assessed in the peri-tumoral region. Correlations between HU changes in various normal lung regions, dose indices (V20, MLD, generalized equivalent uniform dose (gEUD)), and RP grade were investigated. RESULTS: Strong positive correlation was found between HU changes in the peri-tumoral region and RP grade (Spearman's r = 0.760; p < 0.001). Positive correlation was also observed between RP and HU changes in the region covered by V20 for all algorithms (Spearman's r ≥ 0.738; p < 0.001). Additionally, V20, MLD, and gEUD were significantly correlated with RP grade (p < 0.01). MLD in the peri-tumoral region computed with model-based algorithms was 5-7% lower than the PB-based methods. CONCLUSION: Changes of lung density in the peri-tumoral lung and in the region covered by V20 were strongly associated with RP grade. Relative to model-based methods, PB algorithms over-estimated mean peri-tumoral dose and showed displacement of the high-dose region, which correlated with HU changes on follow-up CT scans.

Accuracy of a Robotic Endoscopic System in Cadaver Models with Simulated Tumor Targets: ACCESS Study.

BACKGROUND: Bronchoscopy for the diagnosis of peripheral pulmonary lesions continues to present clinical challenges, despite increasing experience using newer guided techniques. Robotic bronchoscopic platforms have been developed to potentially improve diagnostic yields. Previous studies in cadaver models have demonstrated increased reach into the lung periphery using robotic systems compared to similarly sized conventional bronchoscopes, although the clinical impact of additional reach is unclear. OBJECTIVES: This study was performed to evaluate the performance of a robotic bronchoscopic system's ability to reach and access artificial tumor targets simulating peripheral nodules in human cadaveric lungs. METHODS: Artificial tumor targets sized 10-30 mm in axial diameter were implanted into 8 human cadavers. CT scans were performed prior to procedures and all cadavers were intubated and mechanically ventilated. Electromagnetic navigation, radial probe endobronchial ultrasound, and fluoroscopy were used for all procedures. Robotic-assisted bronchoscopy was performed on each cadaver by an individual bronchoscopist to localize and biopsy peripheral lesions. RESULTS: Sixty-seven nodules were evaluated in 8 cadavers. The mean nodule size was 20.4 mm. The overall diagnostic yield was 65/67 (97%) and there was no statistical difference in diagnostic yield for lesions <20 mm compared with lesions measuring 21-30 mm, the presence of a concentric or eccentric radial ultrasound image, or relative distance from the pleura. CONCLUSIONS: The robotic bronchoscopic system was successful at biopsying 97% of peripheral pulmonary lesions 10-30 mm in size in human cadavers. These findings support further exploration of this technology in prospective clinical trials in live human subjects.

Evaluating Lung Cancer Screening Across Diverse Healthcare Systems: A Process Model from the Lung PROSPR Consortium.

Numerous organizations, including the United States Preventive Services Task Force, recommend annual lung cancer screening (LCS) with low-dose CT for high risk adults who meet specific criteria. Despite recommendations and national coverage for screening eligible adults through the Centers for Medicare and Medicaid Services, LCS uptake in the United States remains low (<4%). In recognition of the need to improve and understand LCS across the population, as part of the larger Population-based Research to Optimize the Screening PRocess (PROSPR) consortium, the NCI (Bethesda, MD) funded the Lung PROSPR Research Consortium consisting of five diverse healthcare systems in Colorado, Hawaii, Michigan, Pennsylvania, and Wisconsin. Using various methods and data sources, the center aims to examine utilization and outcomes of LCS across diverse populations, and assess how variations in the implementation of LCS programs shape outcomes across the screening process. This commentary presents the PROSPR LCS process model, which outlines the interrelated steps needed to complete the screening process from risk assessment to treatment. In addition to guiding planned projects within the Lung PROSPR Research Consortium, this model provides insights on the complex steps needed to implement, evaluate, and improve LCS outcomes in community practice.