Lung cancer risks at which individuals should be screened with computed tomography (CT) for lung cancer are undecided. This study's objectives are to identify a risk threshold for selecting ...individuals for screening, to compare its efficiency with the U.S. Preventive Services Task Force (USPSTF) criteria for identifying screenees, and to determine whether never-smokers should be screened. Lung cancer risks are compared between smokers aged 55-64 and ≥ 65-80 y.
Applying the PLCO(m2012) model, a model based on 6-y lung cancer incidence, we identified the risk threshold above which National Lung Screening Trial (NLST, n = 53,452) CT arm lung cancer mortality rates were consistently lower than rates in the chest X-ray (CXR) arm. We evaluated the USPSTF and PLCO(m2012) risk criteria in intervention arm (CXR) smokers (n = 37,327) of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). The numbers of smokers selected for screening, and the sensitivities, specificities, and positive predictive values (PPVs) for identifying lung cancers were assessed. A modified model (PLCOall2014) evaluated risks in never-smokers. At PLCO(m2012) risk ≥ 0.0151, the 65th percentile of risk, the NLST CT arm mortality rates are consistently below the CXR arm's rates. The number needed to screen to prevent one lung cancer death in the 65th to 100th percentile risk group is 255 (95% CI 143 to 1,184), and in the 30th to <65th percentile risk group is 963 (95% CI 291 to -754); the number needed to screen could not be estimated in the <30th percentile risk group because of absence of lung cancer deaths. When applied to PLCO intervention arm smokers, compared to the USPSTF criteria, the PLCO(m2012) risk ≥ 0.0151 threshold selected 8.8% fewer individuals for screening (p<0.001) but identified 12.4% more lung cancers (sensitivity 80.1% 95% CI 76.8%-83.0% versus 71.2% 95% CI 67.6%-74.6%, p<0.001), had fewer false-positives (specificity 66.2% 95% CI 65.7%-66.7% versus 62.7% 95% CI 62.2%-63.1%, p<0.001), and had higher PPV (4.2% 95% CI 3.9%-4.6% versus 3.4% 95% CI 3.1%-3.7%, p<0.001). In total, 26% of individuals selected for screening based on USPSTF criteria had risks below the threshold PLCO(m2012) risk ≥ 0.0151. Of PLCO former smokers with quit time >15 y, 8.5% had PLCO(m2012) risk ≥ 0.0151. None of 65,711 PLCO never-smokers had PLCO(m2012) risk ≥ 0.0151. Risks and lung cancers were significantly greater in PLCO smokers aged ≥ 65-80 y than in those aged 55-64 y. This study omitted cost-effectiveness analysis.
The USPSTF criteria for CT screening include some low-risk individuals and exclude some high-risk individuals. Use of the PLCO(m2012) risk ≥ 0.0151 criterion can improve screening efficiency. Currently, never-smokers should not be screened. Smokers aged ≥ 65-80 y are a high-risk group who may benefit from screening. Please see later in the article for the Editors' Summary.
Background The detection of pulmonary nodules (PNs) is likely to increase, especially with the release of the National Lung Screen Trials. When tissue diagnosis is desired, transthoracic needle ...aspiration (TTNA) is recommended. Several guided-bronchoscopy technologies have been developed to improve the yield of transbronchial biopsy for PN diagnosis: electromagnetic navigation bronchoscopy (ENB), virtual bronchoscopy (VB), radial endobronchial ultrasound (R-EBUS), ultrathin bronchoscope, and guide sheath. We undertook this meta-analysis to determine the overall diagnostic yield of guided bronchoscopy using one or a combination of the modalities described here. Methods We performed a MEDLINE search using “bronchoscopy” and “solitary pulmonary nodule.” Studies evaluating the diagnostic yield of ENB, VB, R-EBUS, ultrathin bronchoscope, and/or guide sheath for peripheral nodules were included. The overall diagnostic yield and yield based on size were extracted. Adverse events, if reported, were recorded. Meta-analysis techniques incorporating inverse variance weighting and a random-effects meta-analysis approach were used. Results A total of 3,052 lesions from 39 studies were included. The pooled diagnostic yield was 70%, which is higher than the yield for traditional transbronchial biopsy. The yield increased as the lesion size increased. The pneumothorax rate was 1.5%, which is significantly smaller than that reported for TTNA. Conclusion This meta-analysis shows that the diagnostic yield of guided bronchoscopic techniques is better than that of traditional transbronchial biopsy. Although the yield remains lower than that of TTNA, the procedural risk is lower. Guided bronchoscopy may be an alternative or be complementary to TTNA for tissue sampling of PN, but further study is needed to determine its role in the evaluation of peripheral pulmonary lesions.
In the National Lung Screening Trial (NLST), screening with low-dose computed tomography (CT) resulted in a 20% reduction in lung-cancer mortality among participants between the ages of 55 and 74 ...years with a minimum of 30 pack-years of smoking and no more than 15 years since quitting. It is not known whether the benefits and potential harms of such screening vary according to lung-cancer risk.
We assessed the variation in efficacy, the number of false positive results, and the number of lung-cancer deaths prevented among 26,604 participants in the NLST who underwent low-dose CT screening, as compared with the 26,554 participants who underwent chest radiography, according to the quintile of 5-year risk of lung-cancer death (ranging from 0.15 to 0.55% in the lowest-risk group quintile 1 to more than 2.00% in the highest-risk group quintile 5).
The number of lung-cancer deaths per 10,000 person-years that were prevented in the CT-screening group, as compared with the radiography group, increased according to risk quintile (0.2 in quintile 1, 3.5 in quintile 2, 5.1 in quintile 3, 11.0 in quintile 4, and 12.0 in quintile 5; P=0.01 for trend). Across risk quintiles, there were significant decreasing trends in the number of participants with false positive results per screening-prevented lung-cancer death (1648 in quintile 1, 181 in quintile 2, 147 in quintile 3, 64 in quintile 4, and 65 in quintile 5). The 60% of participants at highest risk for lung-cancer death (quintiles 3 through 5) accounted for 88% of the screening-prevented lung-cancer deaths and for 64% of participants with false positive results. The 20% of participants at lowest risk (quintile 1) accounted for only 1% of prevented lung-cancer deaths.
Screening with low-dose CT prevented the greatest number of deaths from lung cancer among participants who were at highest risk and prevented very few deaths among those at lowest risk. These findings provide empirical support for risk-based targeting of smokers for such screening. (Funded by the National Cancer Institute.).
The National Lung Screening Trial (NLST) showed that screening with low-dose computed tomography (CT) as compared with chest radiography reduced lung-cancer mortality. We examined the ...cost-effectiveness of screening with low-dose CT in the NLST.
We estimated mean life-years, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratios (ICERs) for three alternative strategies: screening with low-dose CT, screening with radiography, and no screening. Estimations of life-years were based on the number of observed deaths that occurred during the trial and the projected survival of persons who were alive at the end of the trial. Quality adjustments were derived from a subgroup of participants who were selected to complete quality-of-life surveys. Costs were based on utilization rates and Medicare reimbursements. We also performed analyses of subgroups defined according to age, sex, smoking history, and risk of lung cancer and performed sensitivity analyses based on several assumptions.
As compared with no screening, screening with low-dose CT cost an additional $1,631 per person (95% confidence interval CI, 1,557 to 1,709) and provided an additional 0.0316 life-years per person (95% CI, 0.0154 to 0.0478) and 0.0201 QALYs per person (95% CI, 0.0088 to 0.0314). The corresponding ICERs were $52,000 per life-year gained (95% CI, 34,000 to 106,000) and $81,000 per QALY gained (95% CI, 52,000 to 186,000). However, the ICERs varied widely in subgroup and sensitivity analyses.
We estimated that screening for lung cancer with low-dose CT would cost $81,000 per QALY gained, but we also determined that modest changes in our assumptions would greatly alter this figure. The determination of whether screening outside the trial will be cost-effective will depend on how screening is implemented. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).
Bronchoscopy is frequently nondiagnostic in patients with pulmonary lesions suspected to be lung cancer. This often results in additional invasive testing, although many lesions are benign. We sought ...to validate a bronchial-airway gene-expression classifier that could improve the diagnostic performance of bronchoscopy.
Current or former smokers undergoing bronchoscopy for suspected lung cancer were enrolled at 28 centers in two multicenter prospective studies (AEGIS-1 and AEGIS-2). A gene-expression classifier was measured in epithelial cells collected from the normal-appearing mainstem bronchus to assess the probability of lung cancer.
A total of 639 patients in AEGIS-1 (298 patients) and AEGIS-2 (341 patients) met the criteria for inclusion. A total of 43% of bronchoscopic examinations were nondiagnostic for lung cancer, and invasive procedures were performed after bronchoscopy in 35% of patients with benign lesions. In AEGIS-1, the classifier had an area under the receiver-operating-characteristic curve (AUC) of 0.78 (95% confidence interval CI, 0.73 to 0.83), a sensitivity of 88% (95% CI, 83 to 92), and a specificity of 47% (95% CI, 37 to 58). In AEGIS-2, the classifier had an AUC of 0.74 (95% CI, 0.68 to 0.80), a sensitivity of 89% (95% CI, 84 to 92), and a specificity of 47% (95% CI, 36 to 59). The combination of the classifier plus bronchoscopy had a sensitivity of 96% (95% CI, 93 to 98) in AEGIS-1 and 98% (95% CI, 96 to 99) in AEGIS-2, independent of lesion size and location. In 101 patients with an intermediate pretest probability of cancer, the negative predictive value of the classifier was 91% (95% CI, 75 to 98) among patients with a nondiagnostic bronchoscopic examination.
The gene-expression classifier improved the diagnostic performance of bronchoscopy for the detection of lung cancer. In intermediate-risk patients with a nondiagnostic bronchoscopic examination, a negative classifier score provides support for a more conservative diagnostic approach. (Funded by Allegro Diagnostics and others; AEGIS-1 and AEGIS-2 ClinicalTrials.gov numbers, NCT01309087 and NCT00746759.).
Low-dose chest CT screening for lung cancer has become a standard of care in the United States in the past few years, in large part due to the results of the National Lung Screening Trial. The ...benefit and harms of low-dose chest CT screening differ in both frequency and magnitude. The translation of a favorable balance of benefit and harms into practice can be difficult. Here, we update the evidence base for the benefit, harms, and implementation of low radiation dose chest CT screening. We use the updated evidence base to provide recommendations where the evidence allows, and statements based on experience and expert consensus where it does not.
Approved panelists developed key questions using the PICO (population, intervention, comparator, and outcome) format to address the benefit and harms of low-dose CT screening, as well as key areas of program implementation. A systematic literature review was conducted by using MEDLINE via PubMed, Embase, and the Cochrane Library. Reference lists from relevant retrievals were searched, and additional papers were added. The quality of the evidence was assessed for each critical or important outcome of interest using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Important clinical questions were addressed based on the evidence developed from the systematic literature review. Graded recommendations and ungraded statements were drafted, voted on, and revised until consensus was reached.
The systematic literature review identified 59 studies that informed the response to the 12 PICO questions that were developed. Key clinical questions were addressed resulting in six graded recommendations and nine ungraded consensus based statements.
Evidence suggests that low-dose CT screening for lung cancer results in a favorable but tenuous balance of benefit and harms. The selection of screen-eligible patients, the quality of imaging and image interpretation, the management of screen-detected findings, and the effectiveness of smoking cessation interventions can affect this balance. Additional research is needed to optimize the approach to low-dose CT screening.
BACKGROUND Electromagnetic navigation has improved the diagnostic yield of peripheral bronchoscopy for pulmonary nodules. For these procedures, a thin-slice chest CT scan is performed prior to ...bronchoscopy at full inspiration and is used to create virtual airway reconstructions that are used as a map during bronchoscopy. Movement of the lung occurs with respiratory variation during bronchoscopy, and the location of pulmonary nodules during procedures may differ significantly from their location on the initial planning full-inspiratory chest CT scan. This study was performed to quantify pulmonary nodule movement from full inspiration to end-exhalation during tidal volume breathing in patients undergoing electromagnetic navigation procedures. METHODS A retrospective review of electromagnetic navigation procedures was performed for which two preprocedure CT scans were performed prior to bronchoscopy. One CT scan was performed at full inspiration, and a second CT scan was performed at end-exhalation during tidal volume breathing. Pulmonary lesions were identified on both CT scans, and distances between positions were recorded. RESULTS Eighty-five pulmonary lesions were identified in 46 patients. Average motion of all pulmonary lesions was 17.6 mm. Pulmonary lesions located in the lower lobes moved significantly more than upper lobe nodules. Size and distance from the pleura did not significantly impact movement. CONCLUSIONS Significant movement of pulmonary lesions occurs between full inspiration and end-exhalation during tidal volume breathing. This movement from full inspiration on planning chest CT scan to tidal volume breathing during bronchoscopy may significantly affect the diagnostic yield of electromagnetic navigation bronchoscopy procedures.
Background Optimal performance of bronchoscopy requires patient's comfort, physician's ease of execution, and minimal risk. There is currently a wide variation in the use of topical anesthesia, ...analgesia, and sedation during bronchoscopy. Methods A panel of experts was convened by the American College of Chest Physicians Interventional/Chest Diagnostic Network. A literature search was conducted on MEDLINE from 1969 to 2009, and consensus was reached by the panel members after a comprehensive review of the data. Randomized controlled trials and prospective studies were given highest priority in building the consensus. Results In the absence of contraindications, topical anesthesia, analgesia, and sedation are suggested in all patients undergoing bronchoscopy because of enhanced patient tolerance and satisfaction. Robust data suggest that anticholinergic agents, when administered prebronchoscopy, do not produce a clinically meaningful effect, and their use is discouraged. Lidocaine is the preferred topical anesthetic for bronchoscopy, given its short half life and wide margin of safety. The use of a combination of benzodiazepines and opiates is suggested because of their synergistic effects on patient tolerance during the procedure and the added antitussive properties of opioids. Propofol is an effective agent for sedation in bronchoscopy and can achieve similar sedation, amnesia, and patient tolerance when compared with the combined administration of benzodiazepines and opiates. Conclusions We suggest that all physicians performing bronchoscopy consider using topical anesthesia, analgesic and sedative agents, when feasible. The existing body of literature supports the safety and effectiveness of this approach when the proper agents are used in an appropriately selected patient population.
Endobronchial ultrasound (EBUS) was introduced in the last decade, enabling real-time guidance of transbronchial needle aspiration (TBNA) of mediastinal and hilar structures and parabronchial lung ...masses. The many publications produced about EBUS-TBNA have led to a better understanding of the performance characteristics of this procedure. The goal of this document was to examine the current literature on the technical aspects of EBUS-TBNA as they relate to patient, technology, and proceduralist factors to provide evidence-based and expert guidance to clinicians.
Rigorous methodology has been applied to provide a trustworthy evidence-based guideline and expert panel report. A group of approved panelists developed key clinical questions by using the PICO (population, intervention, comparator, and outcome) format that addressed specific topics on the technical aspects of EBUS-TBNA. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and well-recognized document evaluation tools were used to assess the quality of included studies, to extract meaningful data, and to grade the level of evidence to support each recommendation or suggestion.
Our systematic review and critical analysis of the literature on 15 PICO questions related to the technical aspects of EBUS-TBNA resulted in 12 statements: 7 evidence-based graded recommendations and 5 ungraded consensus-based statements. Three questions did not have sufficient evidence to generate a statement.
Evidence on the technical aspects of EBUS-TBNA varies in strength but is satisfactory in certain areas to guide clinicians on the best conditions to perform EBUS-guided tissue sampling. Additional research is needed to enhance our knowledge regarding the optimal performance of this effective procedure.
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