The objective of this article is to update previous evidence-based recommendations for evaluation and management of individuals with solid pulmonary nodules and to generate new recommendations for ...those with nonsolid nodules.
We updated prior literature reviews, synthesized evidence, and formulated recommendations by using the methods described in the "Methodology for Development of Guidelines for Lung Cancer" in the American College of Chest Physicians Lung Cancer Guidelines, 3rd ed.
We formulated recommendations for evaluating solid pulmonary nodules that measure > 8 mm in diameter, solid nodules that measure ≤ 8 mm in diameter, and subsolid nodules. The recommendations stress the value of assessing the probability of malignancy, the utility of imaging tests, the need to weigh the benefits and harms of different management strategies (nonsurgical biopsy, surgical resection, and surveillance with chest CT imaging), and the importance of eliciting patient preferences.
Individuals with pulmonary nodules should be evaluated and managed by estimating the probability of malignancy, performing imaging tests to better characterize the lesions, evaluating the risks associated with various management alternatives, and eliciting their preferences for management.
Most patients with lung cancer are diagnosed when they present with symptoms, they have advanced stage disease, and curative treatment is no longer an option. An effective screening test has long ...been desired for early detection with the goal of reducing mortality from lung cancer. Sputum cytology, chest radiography, and computed tomography (CT) scan have been studied as potential screening tests. The National Lung Screening Trial (NLST) demonstrated a 20% reduction in mortality with low-dose CT (LDCT) screening, and guidelines now endorse annual LDCT for those at high risk. Implementation of screening is underway with the desire that the benefits be seen in clinical practice outside of a research study format. Concerns include management of false positives, cost, incidental findings, radiation exposure, and overdiagnosis. Studies continue to evaluate LDCT screening and use of biomarkers in risk assessment and diagnosis in attempt to further improve outcomes for patients with lung cancer.
SummaryBackgroundThe US Preventive Services Task Force (USPSTF) recommends lung cancer screening among individuals aged 55–80 years with a 30 pack-year cigarette smoking history and, if they are ...former smokers, those who quit within the past 15 years. Our previous report found that two-thirds of newly diagnosed patients with lung cancer do not meet these criteria; they are reported to be either long-term quitters (≥15 years since quitting) or from a younger age group (age 50–54 years). We aimed to assess survival outcomes in these two subgroups. MethodsFor this prospective, observational cohort study we identified and followed up patients aged 50–80 years with lung cancer, with a smoking history of 30 pack-years or more, and included both current smokers and former smokers who quit within the past 30 years. We identified patients from two cohorts in the USA: a hospital cohort (Mayo Clinic, Rochester, MN) and a community cohort (Olmsted County, MN). Patients were divided into those meeting USPSTF criteria (USPSTF group) versus those not meeting USPSTF criteria (long-term quitters or the younger age group). The main outcome was overall survival at 5 years after diagnosis. 5-year overall survival was analysed with and without matching age and pack-years smoked for long-term quitters. The USPSTF group was subdivided into two age subgroups (55–69 years and 70–80 years) for multivariable regression analysis. FindingsBetween Jan 1, 1997, and Dec 31, 2017, 8739 patients with lung cancer were identified and followed up. Median follow-up was 6·5 (IQR 3·8–10·0) years, and median overall survival was 16·9 months (95% CI 16·2–17·5). 5-year overall survival was 27% (95% CI 25–30) in long-term quitters, 22% (19–25) in the younger age group, and 23% (22–24) in the USPSTF group. In both cohorts, 5-year overall survival did not differ significantly between long-term quitters and the USPSTF group (hospital cohort: hazard ratio HR 1·02 95% CI 0·94–1·10; p=0·72; community cohort: 0·97 0·75–1·26; p=0·82); matched analysis showed similar results in both cohorts. 5-year overall survival also did not differ significantly between the younger age group and the USPSTF group in both cohorts (hospital cohort: HR 1·16 95% CI 0·98–1·38, p=0·08; community cohort: 1·16 0·74–1·82; p=0·52); multivariable regression analyses stratified by age group yielded similar findings. InterpretationPatients with lung cancer who quit 15 or more years before diagnosis and those who are up to 5 years younger than the age cutoff recommended for screening, but otherwise meet USPSTF criteria, have a similar risk of death to those individuals who meet all USPSTF criteria. Individuals in both subgroups could benefit from screening, as expansion of USPSTF screening criteria to include these subgroups could enable earlier detection of lung cancer and improved survival outcomes. FundingNational Institutes of Health and the Mayo Clinic Foundation.
Annual low-radiation-dose computed tomography (LDCT) screening for lung cancer has been shown to reduce lung cancer mortality among high-risk individuals and is now recommended by multiple ...organizations. However, LDCT screening is complex, and implementation requires careful planning to ensure benefits outweigh harms. Little guidance has been provided for sites wishing to develop and implement lung cancer screening programs.
To promote successful implementation of comprehensive LDCT screening programs that are safe, effective, and sustainable.
The American Thoracic Society (ATS) and American College of Chest Physicians (ACCP) convened a committee with expertise in lung cancer screening, pulmonary nodule evaluation, and implementation science. The committee reviewed the evidence from systematic reviews, clinical practice guidelines, surveys, and the experience of early-adopting LDCT screening programs and summarized potential strategies to implement LDCT screening programs successfully.
We address steps that sites should consider during the main three phases of developing an LDCT screening program: planning, implementation, and maintenance. We present multiple strategies to implement the nine core elements of comprehensive lung cancer screening programs enumerated in a recent ACCP/ATS statement, which will allow sites to select the strategy that best fits with their local context and workflow patterns. Although we do not comment on cost-effectiveness of LDCT screening, we outline the necessary costs associated with starting and sustaining a high-quality LDCT screening program.
Following the strategies delineated in this policy statement may help sites to develop comprehensive LDCT screening programs that are safe and effective.
In advanced non-small cell lung cancer (NSCLC), small biopsy specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are often the only available material from ...cancer tissue for the analysis of programmed death ligand-1 (PD-L1) expression. We aim to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression at ≥ 1% and ≥ 50% on EBUS-TBNA samples compared with their corresponding surgically resected tumor.
We retrospectively reviewed all patients who underwent EBUS-TBNA followed by surgical resection of NSCLC between July 2006 and September 2016. Demographic information and periprocedural/surgical data were collected. The archived specimens were retrieved and assessed for PD-L1. A positive PD-L1 stain was defined using two separate cutoff points: ≥ 1% and ≥ 50% of tumor cell positivity. EBUS-TBNA aspirates were compared with the surgically resected specimen to calculate the sensitivity, specificity, PPV, and NPV.
Sixty-one patients were included. For PD-L1 ≥ 1%, the sensitivity, specificity, PPV, and NPV were 72%, 100%, 100%, and 80%, respectively. For PD-L1 ≥ 50%, the sensitivity, specificity, PPV, and NPV were 47%, 93%, 70%, and 84%, respectively. The concordance rates for PD-L1 ≥ 1% and ≥ 50% were 87% and 82%, respectively.
A PD-L1 cutoff of ≥ 1% on EBUS-TBNA has a strong correlation with resected tumor specimen. For PD-L1 ≥ 50%, there is a significant decrease in the sensitivity and PPV of EBUS-TBNA specimen when compared with resected tumor. When analyzing for PD-L1 expression using a cutoff of ≥ 50%, EBUS-TBNA specimens may misclassify the status of PD-L1.
Pulmonary nodules are spherical radiographic opacities that measure up to 30 mm in diameter. Nodules are extremely common in clinical practice and challenging to manage, especially small, ..."subcentimeter" nodules. Identification of malignant nodules is important because they represent a potentially curable form of lung cancer.
We developed evidence-based clinical practice guidelines based on a systematic literature review and discussion with a large, multidisciplinary group of clinical experts and other stakeholders.
We generated a list of 29 recommendations for managing the solitary pulmonary nodule (SPN) that measures at least 8 to 10 mm in diameter; small, subcentimeter nodules that measure < 8 mm to 10 mm in diameter; and multiple nodules when they are detected incidentally during evaluation of the SPN. Recommendations stress the value of risk factor assessment, the utility of imaging tests (especially old films), the need to weigh the risks and benefits of various management strategies (biopsy, surgery, and observation with serial imaging tests), and the importance of eliciting patient preferences.
Patients with pulmonary nodules should be evaluated by estimation of the probability of malignancy, performance of imaging tests to characterize the lesion(s) better, evaluation of the risks associated with various management alternatives, and elicitation of patient preferences for treatment.
To report results of a 5-year prospective low-dose helical chest computed tomographic (CT) study of a cohort at high risk for lung cancer.
After informed written consent was obtained, 1520 ...individuals were enrolled. Protocol was approved by institutional review board and National Cancer Institute and was compliant with Health Insurance Portability and Accountability Act, or HIPAA. Participants were aged 50 years and older and had smoked for more than 20 pack-years. Participants underwent five annual (one initial and four subsequent) CT examinations. A significant downward shift was evaluated in non-small cell lung cancers detected initially from advanced stage down to stage I by using a one-sided binomial test of proportions. Poisson regression and Fisher exact tests were used for comparisons with Mayo Lung Project.
In 788 (52%) men and 732 (48%) women, 61% (927 of 1520) were current smokers, and 39% were former smokers. After five annual CT examinations, 3356 uncalcified lung nodules were identified in 1118 (74%) participants. Sixty-eight lung cancers were diagnosed (31 initial, 34 subsequent, three interval cancers) in 66 participants. Twenty-eight subsequent cases of non-small cell cancers were detected, of which 17 (61%; 95% confidence interval: 41%, 79%) were stage I tumors. Diameter of cancers detected subsequently was 5-50 mm (mean, 14.4 mm; median, 10.0 mm). Analysis for a more than 50% shift in proportion of stage I non-small cell cancer detection did not show statistical significance. Forty-eight participants died of various causes since enrollment. Lung cancer mortality rate for incidence portion of trial was 1.6 per 1000 person-years. There was no significant difference in lung cancer mortality rates of cancers detected in subsequent examinations between this trial and Mayo Lung Project after separation of participants into subsets (2.8 vs 2.0 per 1000 person-years, P = .43).
CT allows detection of early-stage lung cancers. Benign nodule detection rate is high. Results suggest no stage shift.
To retrospectively evaluate the computed tomography (CT)-determined size, morphology, location, morphologic change, and growth rate of incidence and prevalence lung cancers detected in high-risk ...individuals who underwent annual chest CT screening for 5 years and to evaluate the histologic features and stages of these cancers.
The study was institutional review board approved and HIPAA compliant. Informed consent was waived. CT scans of 61 cancers (24 in men, 37 in women; age range, 53-79 years; mean, 65 years) were retrospectively reviewed for cancer size, morphology, and location. Forty-eight cancers were assessed for morphologic change and volume doubling time (VDT), which was calculated by using a modified Schwartz equation. Histologic sections were retrospectively reviewed.
Mean tumor size was 16.4 mm (range, 5.5-52.5 mm). Most common CT morphologic features were as follows: for bronchioloalveolar carcinoma (BAC) (n = 9), ground-glass attenuation (n = 6, 67%) and smooth (n = 3, 33%), irregular (n = 3, 33%), or spiculated (n = 3, 33%) margin; for non-BAC adenocarcinomas (n = 25), semisolid (n = 11, 44%) or solid (n = 12, 48%) attenuation and irregular margin (n = 14, 56%); for squamous cell carcinoma (n = 14), solid attenuation (n = 12, 86%) and irregular margin (n = 10, 71%); for small cell or mixed small and large cell neuroendocrine carcinoma (n = 7), solid attenuation (n = 6, 86%) and irregular margin (n = 5, 71%); for non-small cell carcinoma not otherwise specified (n = 5), solid attenuation (n = 4, 80%) and irregular margin (n = 3, 60%); and for large cell carcinoma (n = 1), solid attenuation and spiculated shape (n = 1, 100%). Attenuation most often (in 12 of 21 cases) increased. Margins most often (in 16 of 20 cases) became more irregular or spiculated. Mean VDT was 518 days. Thirteen of 48 cancers had a VDT longer than 400 days; 11 of these 13 cancers were in women.
Overdiagnosis, especially in women, may be a substantial concern in lung cancer screening.
SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, ...particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19-vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.
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