IMPORTANCE: Pulmonary nodules are identified in approximately 1.6 million patients per year in the US and are detected on approximately 30% of computed tomographic (CT) images of the chest. Optimal ...treatment of an individual with a pulmonary nodule can lead to early detection of cancer while minimizing testing for a benign nodule. OBSERVATIONS: At least 95% of all pulmonary nodules identified are benign, most often granulomas or intrapulmonary lymph nodes. Smaller nodules are more likely to be benign. Pulmonary nodules are categorized as small solid (<8 mm), larger solid (≥8 mm), and subsolid. Subsolid nodules are divided into ground-glass nodules (no solid component) and part-solid (both ground-glass and solid components). The probability of malignancy is less than 1% for all nodules smaller than 6 mm and 1% to 2% for nodules 6 mm to 8 mm. Nodules that are 6 mm to 8 mm can be followed with a repeat chest CT in 6 to 12 months, depending on the presence of patient risk factors and imaging characteristics associated with lung malignancy, clinical judgment about the probability of malignancy, and patient preferences. The treatment of an individual with a solid pulmonary nodule 8 mm or larger is based on the estimated probability of malignancy; the presence of patient comorbidities, such as chronic obstructive pulmonary disease and coronary artery disease; and patient preferences. Management options include surveillance imaging, defined as monitoring for nodule growth with chest CT imaging, positron emission tomography–CT imaging, nonsurgical biopsy with bronchoscopy or transthoracic needle biopsy, and surgical resection. Part-solid pulmonary nodules are managed according to the size of the solid component. Larger solid components are associated with a higher risk of malignancy. Ground-glass pulmonary nodules have a probability of malignancy of 10% to 50% when they persist beyond 3 months and are larger than 10 mm in diameter. A malignant nodule that is entirely ground glass in appearance is typically slow growing. Current bronchoscopy and transthoracic needle biopsy methods yield a sensitivity of 70% to 90% for a diagnosis of lung cancer. CONCLUSIONS AND RELEVANCE: Pulmonary nodules are identified in approximately 1.6 million people per year in the US and approximately 30% of chest CT images. The treatment of an individual with a pulmonary nodule should be guided by the probability that the nodule is malignant, safety of testing, the likelihood that additional testing will be informative, and patient preferences.
The present review is an update of the research and development efforts regarding the use of molecular biomarkers in the lung cancer screening setting. The two main unmet clinical needs, namely, the ...refinement of risk to improve the selection of individuals undergoing screening and the characterization of undetermined nodules found during the computed tomography–based screening process are the object of the biomarkers described in the present review. We first propose some principles to optimize lung cancer biomarker discovery projects. Then, we summarize the discovery and developmental status of currently promising molecular candidates, such as autoantibodies, complement fragments, microRNAs, circulating tumor DNA, DNA methylation, blood protein profiling, or RNA airway or nasal signatures. We also mention other emerging biomarkers or new technologies to follow, such as exhaled breath biomarkers, metabolomics, sputum cell imaging, genetic predisposition studies, and the integration of next-generation sequencing into study of circulating DNA. We also underline the importance of integrating different molecular technologies together with imaging, radiomics, and artificial intelligence. We list a number of completed, ongoing, or planned trials to show the clinical utility of molecular biomarkers. Finally, we comment on future research challenges in the field of biomarkers in the context of lung cancer screening and propose a design of a trial to test the clinical utility of one or several candidate biomarkers.
With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health ...care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.
Volatile organic compounds are able to be detected in the exhaled breath by a variety of sensing techniques. These volatiles may be produced by cellular metabolic processes, or inhaled/absorbed from ...exogenous sources. Lung cancer cells may produce and process these compounds different than normal cells. The differences may be detectable in the breath. The following manuscript will review the evidence supporting the premise that a unique chemical signature can be detected in the breath of patients with lung cancer, discuss the results of studies using mass spectrometry and nonspecific chemical sensing techniques to detect the unique lung cancer signature, and speculate on the advancements that must occur to develop a breath test accurate enough to be clinically useful.
Lung cancer is by far the major cause of cancer deaths largely because in the majority of patients it is at an advanced stage at the time it is discovered, when curative treatment is no longer ...feasible. This article examines the data regarding the ability of screening to decrease the number of lung cancer deaths.
A systematic review was conducted of controlled studies that address the effectiveness of methods of screening for lung cancer.
Several large randomized controlled trials (RCTs), including a recent one, have demonstrated that screening for lung cancer using a chest radiograph does not reduce the number of deaths from lung cancer. One large RCT involving low-dose CT (LDCT) screening demonstrated a significant reduction in lung cancer deaths, with few harms to individuals at elevated risk when done in the context of a structured program of selection, screening, evaluation, and management of the relatively high number of benign abnormalities. Whether other RCTs involving LDCT screening are consistent is unclear because data are limited or not yet mature.
Screening is a complex interplay of selection (a population with sufficient risk and few serious comorbidities), the value of the screening test, the interval between screening tests, the availability of effective treatment, the risk of complications or harms as a result of screening, and the degree with which the screened individuals comply with screening and treatment recommendations. Screening with LDCT of appropriate individuals in the context of a structured process is associated with a significant reduction in the number of lung cancer deaths in the screened population. Given the complex interplay of factors inherent in screening, many questions remain on how to effectively implement screening on a broader scale.
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