Combined medical-interventional approaches for the management of complex fungal balls: a case series as a viable alternative in non-surgical patients.

Intracavitary pulmonary aspergilloma is a persistent and life-threatening infection that carries a mortality rate of up to 15%. It occurs when Aspergillus species gain entry to an existing lung cavity. In the absence of definitive treatment, patients may succumb to severe complications such as massive hemoptysis, cachexia, or secondary infections. Aspergillomas often show limited response to antifungal medications, mainly due to insufficient drug concentrations within the cavities. Surgery is frequently the preferred treatment option, but it poses significant risks, and many individuals are ineligible due to underlying health issues. We present the most extensive non-surgical fungal ball cohort to date, managed using an innovative multimodal strategy that combines antifungal therapy before and after bronchoscopic debulking. This was a cross-sectional observational study. For those who cannot undergo surgery, our medical center has pioneered a multimodal approach to aspergilloma resection. This approach combines bronchoscopic endoscopy with antifungal therapy and has been applied successfully to more than 18 patients that are presented in this series. The median age of the cohort was 58 years (range: 32-73), with an equal sex distribution. The mean percent predicted FEV1 was 65.3%. The mean follow-up duration was 3.6 years (range: 0.5-10 years). The cohort receiving antifungals systematically prior to debridement showed a reduction of the pre-existing cavity (40.38 mm versus 34.02 mm, p = 0.021). Across the 18 patients during the follow-up period, 94% remained recurrence-free (defined by symptoms and radiology). Our study fills a critical knowledge gap regarding the significance of initiating antifungal treatment before bronchoscopic debulking and presents a viable approach in these cases for which there is a current unmet therapeutic need.

The use of both medical and interventional methods to treat difficult fungal masses: A collection of cases showing efficacy for patients who can't undergo surgeryIntracavitary pulmonary aspergilloma is a serious and potentially deadly infection with a death rate of up to 15%. It happens when certain types of fungi invade existing lung cavities. Without proper treatment, patients may experience severe complications like heavy bleeding from the lungs, weight loss, or other infections. Traditional antifungal medications often don't work well because they can't reach high enough concentrations in the cavities. Surgery is usually the best option, but it's risky and not possible for many due to other health problems. Our study introduces a new way to treat aspergilloma without surgery. We've treated a significant number of patients using a combination of antifungal drugs and a procedure called bronchoscopic debulking. This involves removing the fungal growth using a thin tube inserted through the airways. Our research involved observing 18 patients treated this way. They were mostly middle-aged, with equal numbers of men and women. Their lung function was moderately impaired, and we followed them for an average of 3.6 years. We found that giving antifungal drugs before the debulking procedure helped reduce the size of the cavities. After treatment, almost all patients remained free of symptoms and signs of recurrence. This study highlights the importance of starting antifungal therapy before bronchoscopic debulking and offers a promising option for patients who can't have surgery.

Molecular analysis of endobronchial ultrasound needle aspirates in patients with non-small cell lung cancer: Results from the SCOPE database.

OBJECTIVE: Molecular subtyping of non-small cell lung cancer (NSCLC) is critical in the diagnostic evaluation of patients with advanced disease. This study aimed to examine whether samples from endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of intrathoracic lymph nodes and/or lung lesions are adequate for molecular analysis across various institutions. METHODS: We retrospectively reviewed all cases of linear EBUS-TBNA with a final bronchoscopic diagnosis of NSCLC entered in the Stather Canadian Outcomes registry for chest ProcEdures database. The primary outcome was specimen inadequacy rate for each molecular target, as defined by the local laboratory or pathologist. RESULTS: A total of 866 EBUS-TBNA procedures for NSCLC were identified. Specimen inadequacy rates were 3.8% for EGFR, 2.5% for ALK-1 and 3.5% for PD-L1. Largest target size was not different between adequate and inadequate specimens, and rapid onsite evaluation did not increase specimen adequacy rates. One centre using next-generation sequencing for EGFR had lower adequacy rates than 2 others using matrix-assisted laser desorption/ionization time-of-flight mass spectrophotometry. CONCLUSION: EBUS-TBNA specimens have a very low-specimen inadequacy rate for molecular subtyping of non-small cell lung cancer.

Health Care Utilization and Costs in Lung Cancer Screening Participants-A Propensity-Matched Economic Analysis.

Introduction: Lung cancer screening (LCS) for high-risk populations has been firmly established to reduce lung cancer mortality, but concerns exist regarding unintended downstream costs. Methods: Mean health care utilization and costs were compared in the Alberta Lung Cancer Screening Study in a cohort undergoing LCS versus a propensity-matched control group who did not. Results: A cohort of 651 LCS participants was matched to 336 unscreened controls. Over the study period (mean 3.6 y), a modest increase in the number of claims (22.4 versus 21.9 per person-year [PY]; Δ 0.50 [95% confidence interval: 0.15-0.86], p = 0.006) and outpatient visits (4.01 versus 3.50 per PY; Δ 0.51 [0.37-0.65], p <0.0001), but not in inpatient admissions, was noted in the screened cohort. Claims payments, inpatient costs, and cancer care costs were similar in the screening arm versus the unscreened. Outpatient encounter costs per participant were higher in the screened group ($2662.18 versus $2040.67 per PY; Δ -$621.51 [-1118.05 to -124.97], p = 0.014). Removing the additional computed tomography screening examinations rendered differences not significant. Mean total costs were not significantly different at $6461.10 per PY in the screening group and $6125.31 in the unscreened group (Δ -$335.79 [-2009.65 to 1338.07], p = 0.69). Conclusions: Modest increases in outpatient costs are noted in individuals undergoing LCS, in part attributable to the screening examinations, without differences in overall health care costs. Health care costs and utilization seem otherwise similar in individuals participating in LCS and those who do not.

Probability of lung cancer in a population excluded from screening due to low PLCOM2012 risk.

BACKGROUND: Several randomized trials demonstrated have reduced lung cancer mortality with screening using computed tomography. However, there remains debate about the optimal approach for determining screening eligibility, and no evidence yet exists reporting lung cancer rates in those excluded from screening due to too low of a personalized risk. METHODS: This study was based on the Alberta Lung Cancer Screening Study, which received 1737 applicants and enrolled 850 based on the NLST criteria or a PLCOM2012 risk ≥ 1.5%. We excluded 887 applicants who were interested in screening but deemed ineligible. We report lung cancer rates in the screened and unscreened cohorts. RESULTS: We observed 30 and 8 lung cancers in the screened and unscreened groups, respectively. Only 1 of 8 lung cancers were among those considered too low risk (0.14%), while the remaining 7 were among those excluded for other reasons, including symptoms requiring more immediate workup. No NLST eligible but PLCO risk < 1.5% screened individual had a lung cancer detected as part of the study, so that of all applicants contacting the program with risk estimates less than 1.5%, only 1/857 (0.12%) developed lung cancer. CONCLUSION: Our findings indicate that a risk-based approach for screening eligibility is unlikely to miss many lung cancers.

Development and application of an electronic synoptic report for reporting and management of low-dose computed tomography lung cancer screening examination.

BACKGROUND: Interpretation of Low Dose CT scans and protocol driven management of findings is a key aspect of lung cancer screening program performance. Reliable and reproducible methods are needed to communicate radiologists' interpretation to the screening program or clinicians driving management decision. METHODS: We performed an audit of a subset of dictated reports from the PANCAN study to assess for omissions. We developed an electronic synoptic reporting tool for radiologists embedded in a clinical documentation system software. The tool was then used for reporting as part of the Alberta Lung Cancer Screening Study and McGill University Health Centre Pilot Lung Cancer Screening Program. RESULTS: Fifty reports were audited for completeness. At least one omission was noted in 30 (70%) of reports, with a major omission (missing lobe, size, type of nodule in report or actionable incidental finding in recommendation section of report) in 24 (48%). Details of the reporting template and functionality such as automated nodule cancer risk assessment, Lung-RADS category assignment, auto-generated narrative type report as well as personalize participant results letter is provided. A description of the system's performance in its application in 2815 CT reports is then summarized. CONCLUSIONS: We found that narrative type radiologist reports for lung cancer screening CT examinations frequently lacked specific discrete data elements required for management. We demonstrate the successful implementation of a radiology synoptic reporting system for use in lung cancer screening, and the use of this information to drive program management and communications.

Endobronchial Ultrasound Transbronchial Needle Aspiration With a 19-Gauge Needle vs 21- and 22-Gauge Needles for Mediastinal Lymphadenopathy.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used to evaluate mediastinal lymphadenopathy. Studies focusing on malignant lymphadenopathy have compared 21- and 22-gauge (21G and 22G, respectively) needles and have not identified an advantage of one needle size over the other in terms of diagnostic yield. RESEARCH QUESTION: Does the 19-gauge (19G) EBUS needle offer greater diagnostic yield and sensitivity vs the 21G and 22G EBUS needles for a diagnosis of sarcoidosis, lymphoma, or mediastinal lymphadenopathy not yet diagnosed? STUDY DESIGN AND METHODS: This study retrospectively examined records of 730 patients from the Stather Canadian Outcomes Registry for Chest Procedures (SCOPE) database who underwent EBUS-TBNA for a diagnosis of suspected sarcoidosis, lymphoma, or mediastinal lymphadenopathy not yet diagnosed. A propensity score analysis of two groups was performed. One group comprised patients undergoing EBUS-TBNA with a 19G needle, the other with a 21G or 22G needle. Cases for analysis were selected with a 1:2 ratio of 19G vs 21/22G using logistic regression and random matching with all eligible 19G cases included. RESULTS: There were 137 patients (312 targets) in the 19G group and 274 patients (631 targets) in the 21/22G group in the propensity score analysis. The diagnostic yield was 107 of 137 (78.1%) in the 19G group vs 194 of 274 (70.8%) in the 21/22G group (difference, 7.3%; 95% CI, -1.9 to 15.6; P = .116). The sensitivity of EBUS-TBNA for sarcoidosis was 80 of 83 (96.4%) in the 19G group vs 150 of 156 (96.2%) in the 21/22G group (difference, 0.24%; 95% CI, -6.6 to 85.1; P = .93). In patients with a final diagnosis of lymphoma, EBUS was diagnostic in 10 of 13 (76.9%) in the 19G group vs 12 of 12 (100%) in the 21/22G group (difference, 23.1%; 95% CI, -5.4 to 50.3; P = .08). INTERPRETATION: The study did not identify an advantage of the 19G EBUS needle over the 21/22G EBUS needles for diagnostic yield nor sensitivity for sarcoidosis or lymphoma.

USPSTF2013 versus PLCOm2012 lung cancer screening eligibility criteria (International Lung Screening Trial): interim analysis of a prospective cohort study.

BACKGROUND: Lung cancer is a major health problem. CT lung screening can reduce lung cancer mortality through early diagnosis by at least 20%. Screening high-risk individuals is most effective. Retrospective analyses suggest that identifying individuals for screening by accurate prediction models is more efficient than using categorical age-smoking criteria, such as the US Preventive Services Task Force (USPSTF) criteria. This study prospectively compared the effectiveness of the USPSTF2013 and PLCOm2012 model eligibility criteria. METHODS: In this prospective cohort study, participants from the International Lung Screening Trial (ILST), aged 55-80 years, who were current or former smokers (ie, had ≥30 pack-years smoking history or ≤15 quit-years since last permanently quitting), and who met USPSTF2013 criteria or a PLCOm2012 risk threshold of at least 1·51% within 6 years of screening, were recruited from nine screening sites in Canada, Australia, Hong Kong, and the UK. After enrolment, patients were assessed with the USPSTF2013 criteria and the PLCOm2012 risk model with a threshold of at least 1·70% at 6 years. Data were collected locally and centralised. Main outcomes were the comparison of lung cancer detection rates and cumulative life expectancies in patients with lung cancer between USPSTF2013 criteria and the PLCOm2012 model. In this Article, we present data from an interim analysis. To estimate the incidence of lung cancers in individuals who were USPSTF2013-negative and had PLCOm2012 of less than 1·51% at 6 years, ever-smokers in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) who met these criteria and their lung cancer incidence were applied to the ILST sample size for the mean follow-up occurring in the ILST. This trial is registered at ClinicalTrials.gov, NCT02871856. Study enrolment is almost complete. FINDINGS: Between June 17, 2015, and Dec 29, 2020, 5819 participants from the International Lung Screening Trial (ILST) were enrolled on the basis of meeting USPSTF2013 criteria or the PLCOm2012 risk threshold of at least 1·51% at 6 years. The same number of individuals was selected for the PLCOm2012 model as for the USPSTF2013 criteria (4540 [78%] of 5819). After a mean follow-up of 2·3 years (SD 1·0), 135 lung cancers occurred in 4540 USPSTF2013-positive participants and 162 in 4540 participants included in the PLCOm2012 of at least 1·70% at 6 years group (cancer sensitivity difference 15·8%, 95% CI 10·7-22·1%; absolute odds ratio 4·00, 95% CI 1·89-9·44; p<0·0001). Compared to USPSTF2013-positive individuals, PLCOm2012-selected participants were older (mean age 65·7 years [SD 5·9] vs 63·3 years [5·7]; p<0·0001), had more comorbidities (median 2 [IQR 1-3] vs 1 [1-2]; p<0·0001), and shorter life expectancy (13·9 years [95% CI 12·8-14·9] vs 14·8 [13·6-16·0] years). Model-based difference in cumulative life expectancies for those diagnosed with lung cancer were higher in those who had PLCOm2012 risk of at least 1·70% at 6 years than individuals who were USPSTF2013-positive (2248·6 years [95% CI 2089·6-2425·9] vs 2000·7 years [1841·2-2160·3]; difference 247·9 years, p=0·015). INTERPRETATION: PLCOm2012 appears to be more efficient than the USPSTF2013 criteria for selecting individuals to enrol into lung cancer screening programmes and should be used for identifying high-risk individuals who benefit from the inclusion in these programmes. FUNDING: Terry Fox Research Institute, The UBC-VGH Hospital Foundation and the BC Cancer Foundation, the Alberta Cancer Foundation, the Australian National Health and Medical Research Council, Cancer Research UK and a consortium of funders, and the Roy Castle Lung Cancer Foundation for the UK Lung Screen Uptake Trial.

Prevalence and incidence of idiopathic subglottic stenosis in southern and central Alberta: a retrospective cohort study.

BACKGROUND: Subglottic stenosis (SGS) is a reportedly rare disease that causes recurrent severe airway obstruction. Etiologies reported for SGS include idiopathic, iatrogenic, autoimmune, congenital, and traumatic, with variable ratios among different centres. From empiric observation, southern and central Alberta was hypothesized to have a disproportionate distribution of SGS driven by increased idiopathic SGS (iSGS) compared to previous literature. Identification of causative agents of iSGS will help understand and guide future management options, so this study aimed to characterize the demographics of SGS subtypes, define prevalence and incidence rates of iSGS in southern Alberta, and geographically analyze for clustering of iSGS prevalence. METHODS: SGS patients from Alberta census divisions No. 1-9 and 15 were retrospectively reviewed. Patients were subtyped according to etiology of SGS and characterized. Idiopathic SGS prevalence and incidence was assessed; prevalence was further geographically segregated by census division and forward sortation area (FSA). Significant clustering patterns were assessed for using a Global Moran's I analysis. RESULTS: From 2010 to 2019 we identified 250 SGS patients, who were substantially overrepresented by idiopathic patients (80.4%) compared to autoimmune (10.0%), iatrogenic (7.6%), congenital (1.2%), and traumatic (0.8%). The total iSGS prevalence was 9.28/100,000 with a mean annual incidence rate of 0.71/100,000 per year. Significant clustering was observed (Moran's index 0.125; z-score 2.832; p = 0.0046) and the highest rates of prevalence were observed in southern Alberta and in rural communities heterogeneously dispersed around Calgary FSAs. CONCLUSION: In southern and central Alberta, iSGS patients were disproportionately over-represented in contrast to other subtypes with the highest prevalence in southern Alberta. There was a three-fold higher annual incidence compared to previous literature demonstrating the highest rates of disease reported worldwide. Future research aims to expand the geographical scope and to assess for demographic or environmental differences within significant clusters that may contribute to disease pathophysiology. LEVEL OF EVIDENCE: III.

Two-Year Follow-Up of a Randomized Controlled Study of Integrated Smoking Cessation in a Lung Cancer Screening Program.

INTRODUCTION: Smoking cessation activities incorporated into lung cancer screening programs have been broadly recommended, but studies to date have not exhibited increased quit rates associated with cessation programs in this setting. We aimed to determine the long-term effectiveness of smoking cessation counseling in smokers presenting for lung cancer screening. METHODS: This was a randomized control trial of an intensive, telephone-based smoking cessation counseling intervention incorporating lung cancer screening results versus usual care (information pamphlet). This analysis reports on the long-term impact (24-mo) of the intervention on abstinence from smoking. RESULTS: A total of 337 active smokers who participated in the screening study were randomized to active smoking cessation counseling (n = 171) or control arm (n = 174) and completed a 24-month assessment. The 30-day smoking abstinence rates at 24 months postrandomization was 18.3% and 21.4% in the control and intervention arms, respectively-a 3.1% difference (95% confidence interval: -5.4 to 11.6, p = 0.48). No statistically significant differences in the 7-day abstinence, the use of pharmacologic cessation aids, nicotine replacement therapies, nor intent to quit in the following 30 days were noted (p > 0.05). The abstinence rates at 24-months were higher overall than at 12-months (19.9% versus 13.3%, p < 0.001), and smoking intensity was lower than at baseline for ongoing smokers. CONCLUSIONS: A telephone-based smoking cessation counseling intervention incorporating lung cancer screening results did not result in increased long-term cessation rates versus written information alone in unselected smokers undergoing lung cancer screening. Overall, quit rates were high and continued to improve throughout participation in the screening program. (ClinicalTrials.govNCT02431962).

Protocol for the Stather Canadian Outcomes Registry for Chest ProcedurEs (SCOPE).

INTRODUCTION: The Stather Canadian Outcomes registry for chest ProcedurEs (SCOPE registry) is a Canadian multicentre registry of chest procedures. METHODS AND ANALYSIS: The SCOPE registry is designed as a multicentre prospective database of specific bronchoscopic or other pulmonary procedures. Each procedure of interest will be associated with a registry module, and data capture designed to evaluate effectiveness of procedures on relevant patient outcomes. Participating physicians will be asked to enter data for all procedures performed in a given module. The anonymised dataset will be housed in a web-based electronic secure database. Specific modules included will be based on participating physician suggestions, capacity and consensus of the steering committee and relevance of hypotheses/research potential. ETHICS AND DISSEMINATION: The central registry is under approval from the Conjoint Health Research Ethics Board at the University of Calgary. We aim for registry data to lead to publication of manuscripts in international medical journals as the primary mode of dissemination. Data may also be used by local investigators for personal and/or institutional quality control purposes as well as to inform health policies. Data requests from non-participating investigators for use under ethics approved research protocols can be considered.

Does prior mediastinal lymph node aspiration contribute to false-positive positron emission tomography-computed tomography?

BACKGROUND: Proper staging of the mediastinum is an essential component of lung cancer evaluation. Positron emission tomography-computed tomography (PETCT) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) are an integral part of this process. False-positive PETCT results can occur following surgical procedures but has not been demonstrated following EBUS-TBNA. We aimed to determine whether false-positive PETCT rates increase when EBUS-TBNA is performed prior to PETCT. STUDY DESIGN AND METHODS: A retrospective review was carried out of clinical cases that underwent both PETCT and EBUS-TBNA within 30 days for the suspected malignancy. The impact of test sequence on the PETCT false-positive rate (FPR) was determined using Generalised Estimating Equation logistic regression analysis. RESULTS: A total of 675 lymph node stations were sampled and imaged on PETCT. Overall, 332 (49.2%) nodes were sampled by EBUS-TBNA before PETCT, and 343 (50.8%) afterwards, with the interval between EBUS and subsequent PETCT being a mean±sd of 11.6±6.8 days (range 1-29). The FPR on qualitative PETCT for the EBUS first group was 41 (23.2%) out of 164, and for PETCT first it was 57 (29.0%) out of 193 for a difference of 5.8% (95% CI -3.4-14.7, p=0.22). In the regression model, EBUS as the first test was associated with a lower FPR when using the clinical PETCT interpretation. INTERPRETATION: The performance of EBUS-TBNA sampling did not influence the FPR of PETCT when bronchoscopy took place in the 30 days prior to testing. Test sequence should be selected based on other clinical considerations.

Application of Lung-Screening Reporting and Data System Versus Pan-Canadian Early Detection of Lung Cancer Nodule Risk Calculation in the Alberta Lung Cancer Screening Study.

BACKGROUND: False-positive scans and resultant needless early recalls can increase harms and reduce cost-effectiveness of low-dose CT (LDCT) lung cancer screening. How LDCT scans are interpreted and classified may impact these metrics. METHODS: The Pan-Canadian Early Detection of Lung Cancer risk calculator was used to determine nodule risk of malignancy on baseline screening LDCTs in the Alberta Lung Cancer Screening Study, which were then classified according to Nodule Risk Classification (NRC) categories and ACR Lung Screening Reporting and Data System (Lung-RADS). Test performance characteristics and early recall rates were compared for each approach. RESULTS: In all, 775 baseline screens were analyzed. After a mean of 763 days (±203) of follow-up, lung cancer was detected in 22 participants (2.8%). No statistically significant differences in sensitivity, specificity, or area under the receiver operator characteristic curve occurred between the NRC and Lung-RADS nodule management approaches. Early recall rates were 9.2% and 9.3% for NRC and Lung-RADS, with the NRC unnecessarily recalling some ground glass nodules, and the Lung-RADS recalling many smaller solid nodules with low risk of malignancy. CONCLUSION: Performances of both the NRC and Lung-RADS in this cohort were very good with a trend to higher sensitivity for the NRC. Early recall rates were less than 10% with each approach, significantly lower than rates using the National Lung Screening Trial cutoffs. Further reductions in early recall rates without compromising sensitivity could be achieved by increasing the NRC threshold to 20% for ground glass nodules or by applying the nodule risk calculator with a 5% threshold to 6- to 10-mm solid nodules under Lung-RADS.

A Randomized Controlled Study of Integrated Smoking Cessation in a Lung Cancer Screening Program.

INTRODUCTION: Smoking cessation activities incorporated into lung cancer screening programs have been broadly recommended, but studies to date have not shown increased quit rates associated with cessation programs in this setting. We aimed to determine the effectiveness of smoking cessation counseling in smokers presenting for lung cancer screening. METHODS: This study is a randomized control trial of an intensive telephone-based smoking cessation counseling intervention incorporating lung cancer screening results versus usual care (information pamphlet). All active smokers enrolled in the Alberta Lung Cancer Screening Study cohort were randomized on a 1:1 ratio with a primary endpoint of self-reported 30-day abstinence at 12 months. RESULTS: A total of 345 active smokers participating in the screening study were randomized to active smoking cessation counseling (n = 171) or control arm (n = 174). Thirty-day smoking abstinence at 12 months post-randomization was noted in 22 of 174 (12.6%) and 24 of 171 (14.0%) of participants in the control and intervention arms, respectively, a 1.4% difference (95% confidence interval: -5.9 to 8.7, p = 0.7). No statistically significant differences in 7-day or point abstinence were noted, nor were differences at 6 months or 24 months. CONCLUSIONS: A telephone-based smoking cessation counseling intervention incorporating lung cancer screening results did not result in increased 12-month cessation rates versus written information alone in unselected smokers undergoing lung cancer screening. Routine referral of all current smokers to counseling-based cessation programs may not improve long-term cessation in this patient cohort. Future studies should specifically focus on this subgroup of older long-term smokers to determine the optimal method of integrating smoking cessation with lung cancer screening (clinicaltrials.govNCT02431962).

Health-related quality of life and anxiety in the PAN-CAN lung cancer screening cohort.

OBJECTIVES: The impact of lung cancer screening with low-dose chest CT (LDCT) on participants' anxiety levels and health-related quality of life (HRQoL) is an important consideration in the implementation of such programmes. We aimed to describe changes in anxiety and HRQoL in a high-risk Canadian cohort undergoing LDCT lung cancer screening. METHODS: 2537 subjects who had 2% or greater lung cancer risk over 6 years using a risk prediction tool were recruited from eight centres across Canada in the Pan-Canadian Early Detection of Lung Cancer Study (2008-2010). We compared HRQoL and anxiety levels before and after screening of 1237 participants with LDCT (excluding a subset of 1300 participants who also underwent autofluorescence bronchoscopy screening), as well as after investigations performed because of a positive screening examination. The 12-item short-form Physical and Mental Component Scales (SF-12), EQ-5D-3L scores and State Trait Anxiety Inventory-State anxiety were used at each assessment. RESULTS: Overall, there were no clinically significant differences in HRQoL outcomes between baseline and each of the survey time points following initial screening. No mean change in anxiety in the overall cohort was noted following baseline LDCT, but more participants had clinically significant increase in anxiety versus decrease after baseline screening (increase >minimal clinically important difference (MCID) (n=180) vs decrease >MCID (n=50), p<0.001). This finding persisted but to a lesser degree at the 12 month time point (increase >MCID (n=146) vs decrease >MCID (n=87), p<0.001). CONCLUSIONS: CT screening for lung cancer has no major overall impact on HRQoL among participants, although a minority of participants (number-needed-to-harm=7 after baseline screening and 18 at 1 year) demonstrated clinically significant increased anxiety levels. TRIALREGISTRATION NUMBER: NCT00751660; Results.

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration With a 19-G Needle Device.

BACKGROUND: Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration is a well-established first-line minimally invasive modality for mediastinal lymph node sampling. Although results are excellent overall, the technique underperforms in certain situations. We aimed to describe our results using a new 19-G EBUS-guided transbronchial needle aspiration device to determine safety and feasibility of this approach. METHODS: We completed a retrospective chart review of all cases performed to the time of data analysis at each of 3 study sites. RESULTS: A total of 165 procedures were performed with a total of 297 individual lymph nodes or lesions sampled with the 19-G device by 10 bronchoscopists. Relatively large targets were selected for sampling with the device (mean lymph node size: 20.4 mm; lung lesions: 33.5 mm). A specific diagnosis was obtained in 77.3% of cases with an additional 13.6% of cases with benign lymphocytes, for a procedural adequacy rate of 90.9%. Procedure sample adequacy was 88.6% in suspected malignant cases, 91.0% in suspected sarcoidosis/lymphadenopathy cases, and 85.7% of cases with suspected lymphoma. On a per-node basis, a specific diagnosis was noted in 191/280 (68.2%) of samples, with an additional 61 showing benign lymphocytes for a per-node sample adequacy rate of 90%. One case (0.6%) of intraprocedure bleeding was noted. CONCLUSIONS: A new flexible 19-G EBUS needle was successfully and safely applied in a large patient cohort for sampling of lung and enlarged mediastinal lesions with high diagnostic rates across clinical indications.

Initial Clinical Experience With a Flexible Peripheral 21-G Needle Device.

BACKGROUND: Bronchoscopic techniques can be used to safely sample peripheral lung nodules (PLN), and transbronchial needle aspiration (TBNA) can further increase the diagnostic yield. Current needle devices not necessarily designed for this indication have limitations. We report our initial experience with a new flexible nitinol peripheral TBNA needle specifically designed for such sampling. METHODS: Retrospective case review describing the first clinical cases performed with a commercially available 21-G peripheral TBNA device in 4 centers. RESULTS: Eleven different operators performed 40 procedures for PLNs of a mean size of 35.1 mm (±18), and located 18.8 mm (±18.8) from the pleural surface, with 50% of them being present in the upper lobes. Bronchoscopists rated the use of the needle as good or excellent for reaching the PLN in 27/30 (90%) of cases. The TBNA sample was diagnostic in 18/40 cases (45%) overall and in 18/28 (64.3%) of cases where a diagnosis on bronchoscopy was possible. No episode of pneumothorax, significant bleeding, hypoxemia, escalation of care, or other complications were noted. CONCLUSION: Our initial experience with a novel peripheral TBNA device appears safe and effective, and may offer technical advantages over other available devices. Additional studies will be required to confirm the role of this device in the approach to bronchoscopic sampling of parenchymal lung nodules.

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

BACKGROUND: Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. METHODS: We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. FINDINGS: 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer): one diagnosed between T0 and T1, and nine between T1 and T4. Cumulative incidence was significantly higher than that observed in NLST (4·0%; p<0·0001). Compared with 593 (57%) of 1040 lung cancers observed in NLST, 133 (77%) of 172 lung cancers in the PanCan Study were early stage (I or II; p<0·0001). INTERPRETATION: The PanCan model was effective in identifying individuals who were subsequently diagnosed with early, potentially curable, lung cancer. The incidence of cancers detected and the proportion of early stage cancers in the screened population was higher than observed in previous studies. This approach should be considered for adoption in lung cancer screening programmes. FUNDING: Terry Fox Research Institute and Canadian Partnership Against Cancer.

Beyond disease-progression: Clinical outcomes after EGFR-TKIs in a cohort of EGFR mutated NSCLC patients.

PURPOSE: Treatment and clinical-outcomes were described in a sub-cohort of non-small-cell lung cancer (NSCLC) patients with disease-progression (PD) after epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment. PATIENTS AND METHODS: We retrospectively analyzed a single-institutional EGFR mutation positive (EGFRmut+) NSCLC cohort for post-TKI-PD management, and assessed overall survival (OS) and post-progression survival (PPS). All de-novo (first lung-cancer occurrence) stage IIIA-IV patients, as well as de-novo stage IV subset was analyzed. Multi-state modeling (MSM) and a Cox PH regression model with propensity score weights adjusted for clinicopathological variables between: diagnosis and PD and PD to death. RESULTS: 123 stage IIIA-IV patients were identified with 104 meeting RECIST-1.1-PD criteria. This RECIST-1.1-PD criteria subset included females (64.6%), Asians (39.4%), never/non-smokers (55.8%), and exon 19 deletion carriers (44.2%). Commonest treatment beyond initial-PD was continuing TKI alone (46/104), with another 21 patients continuing TKI plus additional systemic therapy. The median OS for patients who continued TKI treatment at initial-PD was 21.1 months versus 15.6 months for patients who discontinued TKI, p = 0.006. Via MSM analysis, continuing TKI at initial-PD followed by other systemic therapy was associated with an 83% reduced death risk, adjusted HR: 0.17 (95% CI: 0.07, 0.39). In the Cox PH model, ever-smokers with an exon 19 deletion had increased risk of death after PD (adjusted HR: 3.19, 95% CI: 1.54, 6.58), as did exon 21 mutation carriers, (adjusted HR: 2.10, 95% CI: 1.10, 4.00) and females (adjusted HR: 3.19, 95% CI: 1.54, 6.58). CONCLUSION: Subsequent systemic therapy after continuing TKI at initial-PD reduced the risk of death. Additionally, our data suggest that positive smoking history increases death risk for some EGFR mutation types and females.

Tobacco use and motivation to stop smoking among long-term smokers who are ineligible for lung cancer screening.

BACKGROUND: The importance of smoking cessation interventions in lung cancer screening participants has been highlighted. This study aimed to describe the smoking habits of individuals who were ineligible for lung cancer screening and to investigate whether this encounter may represent an opportunity to reduce tobacco use. METHODS: Ever smokers between the ages of 55 and 80 and ≥1.5% lung cancer risk over 6 years or having smoked ≥30 pack-years and with no more than 15 years of smoking abstinence were eligible to participate in the Alberta Lung Cancer Screening Program (ALCSP). A baseline questionnaire exploring tobacco use was administered to all interested individuals as part of the eligibility determination for the program. RESULTS: Among 504 individuals, 254 (50.4%) met the criteria for the ALCSP and 250 (49.6%) were non-eligible for screening. Non-eligible individuals were slightly younger (mean=60.2 vs. 63.1 years, p-value <0.001), and less likely to be current smokers (26.0% vs. 48.8%, p-value <0.001). Non-eligible smokers had a lower degree of addiction compared to eligible group, as measured by the Fagerström Test of Nicotine Dependence (Median=4.0 vs 6.0, p-value=0.001), but still in the "moderately dependent" range for this test. There were no significant differences in motivation to quit (98.5% vs. 97.6%, p-value=0.689), or motivation to receive help with their quit attempt (89.2% vs. 90.3%, p-value=0.813) between these two groups. Only 7.7% of non-eligible and 2.4% of eligible current smokers were currently in a smoking cessation program. CONCLUSION: A significant proportion of individuals applying to, but not qualifying for a lung cancer screening program are active smokers with significant nicotine dependence. Very few are currently participating in active smoking cessation programs but almost all are interested in quitting and in receiving help with quit attempts. Future studies need to investigate the most effective approaches for smoking cessation in this substantial group of older, long-term smokers, capitalizing on their motivation to receive cessation assistance.