-
Respiratory Medicine Aug 2023Pulmonary nodules are often discovered incidentally during CT scans performed for other reasons. While the vast majority of nodules are benign, a small percentage may... (Review)
Review
Pulmonary nodules are often discovered incidentally during CT scans performed for other reasons. While the vast majority of nodules are benign, a small percentage may represent early-stage lung cancer with the potential for curative treatments. With the growing use of CT for both clinical purposes and lung cancer screening, the number of pulmonary nodules detected is expected to increase substantially. Despite well-established guidelines, many nodules do not receive proper evaluation due to a variety of factors, including inadequate coordination of care and financial and social barriers. To address this quality gap, novel approaches such as multidisciplinary nodule clinics and multidisciplinary boards may be necessary. As pulmonary nodules may indicate early-stage lung cancer, it is crucial to adopt a risk-stratified approach to identify potential lung cancers at an early stage, while minimizing the risk of harm and expense associated with over investigation of low-risk nodules. This article, authored by multiple specialists involved in nodule management, delves into the diagnostic approach to lung nodules. It covers the process of determining whether a patient requires tissue sampling or continued surveillance. Additionally, the article provides an in-depth examination of the various biopsy and therapeutic options available for malignant lung nodules. The article also emphasizes the significance of early detection in reducing lung cancer mortality, especially among high-risk populations. Furthermore, it addresses the creation of a comprehensive lung nodule program, which involves smoking cessation, lung cancer screening, and systematic evaluation and follow-up of both incidental and screen-detected nodules.
Topics: Humans; Lung Neoplasms; Early Detection of Cancer; Lung; Multiple Pulmonary Nodules; Tomography, X-Ray Computed; Solitary Pulmonary Nodule
PubMed: 37187432
DOI: 10.1016/j.rmed.2023.107277 -
Journal of the American College of... Mar 2024The ACR created the Lung CT Screening Reporting and Data System (Lung-RADS) in 2014 to standardize the reporting and management of screen-detected pulmonary nodules....
The ACR created the Lung CT Screening Reporting and Data System (Lung-RADS) in 2014 to standardize the reporting and management of screen-detected pulmonary nodules. Lung-RADS was updated to version 1.1 in 2019 and revised size thresholds for nonsolid nodules, added classification criteria for perifissural nodules, and allowed for short-interval follow-up of rapidly enlarging nodules that may be infectious in etiology. Lung-RADS v2022, released in November 2022, provides several updates including guidance on the classification and management of atypical pulmonary cysts, juxtapleural nodules, airway-centered nodules, and potentially infectious findings. This new release also provides clarification for determining nodule growth and introduces stepped management for nodules that are stable or decreasing in size. This article summarizes the current evidence and expert consensus supporting Lung-RADS v2022.
Topics: Humans; Lung Neoplasms; Tomography, X-Ray Computed; Consensus; Cysts; Lung
PubMed: 37820837
DOI: 10.1016/j.jacr.2023.09.009 -
Journal of Clinical Oncology : Official... Dec 2023The genomic underpinnings of inherited lung cancer risk are poorly understood. This prospective study characterized the clinical phenotype of patients and families with...
PURPOSE
The genomic underpinnings of inherited lung cancer risk are poorly understood. This prospective study characterized the clinical phenotype of patients and families with germline pathogenic variants (PVs).
METHODS
The Investigating Hereditary Risk from T790M study (ClinicalTrials.gov identifier: NCT01754025) enrolled patients with lung cancer whose tumor profiling harbored possible germline PVs and their relatives, either in person or remotely, providing germline testing and follow-up.
RESULTS
A total of 141 participants were enrolled over a 5-year period, 100 (71%) remotely. Based upon previous genotyping, 116 participants from 59 kindreds were tested for T790M, demonstrating a pattern of Mendelian inheritance with variable lung cancer penetrance. In confirmed or obligate carriers of a germline PV from 39 different kindreds, 50/91 (55%) were affected with lung cancer with 34/65 (52%) diagnosed by age 60 years. Somatic testing of lung cancers in carriers revealed that 35 of 37 (95%) had an driver comutation. Among 36 germline carriers without a cancer diagnosis, 15 had computed tomography (CT) imaging and nine had lung nodules, including a 28-year-old with >10 lung nodules. Given geographic enrichment of germline T790M in the southeast United States, genome-wide haplotyping of 46 germline carriers was performed and identified a 4.1-Mb haplotype shared by 41 (89%), estimated to originate 223-279 years ago.
CONCLUSION
To our knowledge, this is the first prospective description of familial -mutant lung cancer, identifying a recent founder germline T790M variant enriched in the Southeast United States. The high prevalence of -driver lung adenocarcinomas and lung nodules in germline carriers supports effort to identify affected patients and family members for investigation of CT-based screening for these high-risk individuals.
Topics: Humans; Middle Aged; Adult; Lung Neoplasms; Prospective Studies; ErbB Receptors; Mutation; Protein Kinase Inhibitors; Germ-Line Mutation; Lung
PubMed: 37579253
DOI: 10.1200/JCO.23.01372 -
Journal of the National Cancer Institute Sep 2023Although lung cancer screening with low-dose computed tomography is rolling out in many areas of the world, differentiating indeterminate pulmonary nodules remains a...
BACKGROUND
Although lung cancer screening with low-dose computed tomography is rolling out in many areas of the world, differentiating indeterminate pulmonary nodules remains a major challenge. We conducted one of the first systematic investigations of circulating protein markers to differentiate malignant from benign screen-detected pulmonary nodules.
METHODS
Based on 4 international low-dose computed tomography screening studies, we assayed 1078 protein markers using prediagnostic blood samples from 1253 participants based on a nested case-control design. Protein markers were measured using proximity extension assays, and data were analyzed using multivariable logistic regression, random forest, and penalized regressions. Protein burden scores (PBSs) for overall nodule malignancy and imminent tumors were estimated.
RESULTS
We identified 36 potentially informative circulating protein markers differentiating malignant from benign nodules, representing a tightly connected biological network. Ten markers were found to be particularly relevant for imminent lung cancer diagnoses within 1 year. Increases in PBSs for overall nodule malignancy and imminent tumors by 1 standard deviation were associated with odds ratios of 2.29 (95% confidence interval: 1.95 to 2.72) and 2.81 (95% confidence interval: 2.27 to 3.54) for nodule malignancy overall and within 1 year of diagnosis, respectively. Both PBSs for overall nodule malignancy and for imminent tumors were substantially higher for those with malignant nodules than for those with benign nodules, even when limited to Lung Computed Tomography Screening Reporting and Data System (LungRADS) category 4 (P < .001).
CONCLUSIONS
Circulating protein markers can help differentiate malignant from benign pulmonary nodules. Validation with an independent computed tomographic screening study will be required before clinical implementation.
Topics: Humans; Lung Neoplasms; Proteome; Early Detection of Cancer; Solitary Pulmonary Nodule; Lung; Multiple Pulmonary Nodules
PubMed: 37369027
DOI: 10.1093/jnci/djad122 -
Ugeskrift For Laeger Apr 2024Lung cancer is the leading cause of cancer-related death in Denmark and the world. The increase in CT examinations has led to an increase in detection of pulmonary... (Review)
Review
Lung cancer is the leading cause of cancer-related death in Denmark and the world. The increase in CT examinations has led to an increase in detection of pulmonary nodules divided into solid and subsolid (including ground glass and part solid). Risk factors for malignancy include age, smoking, female gender, and specific ethnicities. Nodule traits like size, spiculation, upper-lobe location, and emphysema correlate with higher malignancy risk. Managing these potentially malignant nodules relies on evidence-based guidelines and risk stratification. These risk stratification models can standardize the approach for the management of incidental pulmonary findings, as argued in this review.
Topics: Humans; Female; Tomography, X-Ray Computed; Solitary Pulmonary Nodule; Multiple Pulmonary Nodules; Lung Neoplasms; Lung
PubMed: 38606710
DOI: 10.61409/V09230595 -
The Lancet. Respiratory Medicine Aug 2023Lung cancer is the second most common cancer in incidence and the leading cause of cancer deaths worldwide. Meanwhile, lung cancer screening with low-dose CT can reduce...
Predicting the future risk of lung cancer: development, and internal and external validation of the CanPredict (lung) model in 19·67 million people and evaluation of model performance against seven other risk prediction models.
BACKGROUND
Lung cancer is the second most common cancer in incidence and the leading cause of cancer deaths worldwide. Meanwhile, lung cancer screening with low-dose CT can reduce mortality. The UK National Screening Committee recommended targeted lung cancer screening on Sept 29, 2022, and asked for more modelling work to be done to help refine the recommendation. This study aims to develop and validate a risk prediction model-the CanPredict (lung) model-for lung cancer screening in the UK and compare the model performance against seven other risk prediction models.
METHODS
For this retrospective, population-based, cohort study, we used linked electronic health records from two English primary care databases: QResearch (Jan 1, 2005-March 31, 2020) and Clinical Practice Research Datalink (CPRD) Gold (Jan 1, 2004-Jan 1, 2015). The primary study outcome was an incident diagnosis of lung cancer. We used a Cox proportional-hazards model in the derivation cohort (12·99 million individuals aged 25-84 years from the QResearch database) to develop the CanPredict (lung) model in men and women. We used discrimination measures (Harrell's C statistic, D statistic, and the explained variation in time to diagnosis of lung cancer [R]) and calibration plots to evaluate model performance by sex and ethnicity, using data from QResearch (4·14 million people for internal validation) and CPRD (2·54 million for external validation). Seven models for predicting lung cancer risk (Liverpool Lung Project [LLP], LLP, Lung Cancer Risk Assessment Tool [LCRAT], Prostate, Lung, Colorectal, and Ovarian [PLCO], PLCO, Pittsburgh, and Bach) were selected to compare their model performance with the CanPredict (lung) model using two approaches: (1) in ever-smokers aged 55-74 years (the population recommended for lung cancer screening in the UK), and (2) in the populations for each model determined by that model's eligibility criteria.
FINDINGS
There were 73 380 incident lung cancer cases in the QResearch derivation cohort, 22 838 cases in the QResearch internal validation cohort, and 16 145 cases in the CPRD external validation cohort during follow-up. The predictors in the final model included sociodemographic characteristics (age, sex, ethnicity, Townsend score), lifestyle factors (BMI, smoking and alcohol status), comorbidities, family history of lung cancer, and personal history of other cancers. Some predictors were different between the models for women and men, but model performance was similar between sexes. The CanPredict (lung) model showed excellent discrimination and calibration in both internal and external validation of the full model, by sex and ethnicity. The model explained 65% of the variation in time to diagnosis of lung cancer R in both sexes in the QResearch validation cohort and 59% of the R in both sexes in the CPRD validation cohort. Harrell's C statistics were 0·90 in the QResearch (validation) cohort and 0·87 in the CPRD cohort, and the D statistics were 2·8 in the QResearch (validation) cohort and 2·4 in the CPRD cohort. Compared with seven other lung cancer prediction models, the CanPredict (lung) model had the best performance in discrimination, calibration, and net benefit across three prediction horizons (5, 6, and 10 years) in the two approaches. The CanPredict (lung) model also had higher sensitivity than the current UK recommended models (LLP and PLCO), as it identified more lung cancer cases than those models by screening the same amount of individuals at high risk.
INTERPRETATION
The CanPredict (lung) model was developed, and internally and externally validated, using data from 19·67 million people from two English primary care databases. Our model has potential utility for risk stratification of the UK primary care population and selection of individuals at high risk of lung cancer for targeted screening. If our model is recommended to be implemented in primary care, each individual's risk can be calculated using information in the primary care electronic health records, and people at high risk can be identified for the lung cancer screening programme.
FUNDING
Innovate UK (UK Research and Innovation).
TRANSLATION
For the Chinese translation of the abstract see Supplementary Materials section.
Topics: Male; Humans; Female; Cohort Studies; Lung Neoplasms; Risk Assessment; Early Detection of Cancer; Retrospective Studies; Prospective Studies; Lung; Risk Factors
PubMed: 37030308
DOI: 10.1016/S2213-2600(23)00050-4 -
The Journal of Thoracic and... Dec 2023The study objective was to determine the clinical utility of pafolacianine, a folate receptor-targeted fluorescent agent, in revealing by intraoperative molecular... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The study objective was to determine the clinical utility of pafolacianine, a folate receptor-targeted fluorescent agent, in revealing by intraoperative molecular imaging folate receptor α positive cancers in the lung and narrow surgical margins that may otherwise be undetected with conventional visualization.
METHODS
In this Phase 3, 12-center trial, 112 patients with suspected or biopsy-confirmed cancer in the lung scheduled for sublobar pulmonary resection were administered intravenous pafolacianine within 24 hours before surgery. Participants were randomly assigned to surgery with or without intraoperative molecular imaging (10:1 ratio). The primary end point was the proportion of participants with a clinically significant event, reflecting a meaningful change in the surgical operation.
RESULTS
No drug-related serious adverse events occurred. One or more clinically significant event occurred in 53% of evaluated participants compared with a prespecified limit of 10% (P < .0001). In 38 participants, at least 1 event was a margin 10 mm or less from the resected primary nodule (38%, 95% confidence interval, 28.5-48.3), 32 being confirmed by histopathology. In 19 subjects (19%, 95% confidence interval, 11.8-28.1), intraoperative molecular imaging located the primary nodule that the surgeon could not locate with white light and palpation. Intraoperative molecular imaging revealed 10 occult synchronous malignant lesions in 8 subjects (8%, 95% confidence interval, 3.5-15.2) undetected using white light. Most (73%) intraoperative molecular imaging-discovered synchronous malignant lesions were outside the planned resection field. A change in the overall scope of surgical procedure occurred for 29 of the subjects (22 increase, 7 decrease).
CONCLUSIONS
Intraoperative molecular imaging with pafolacianine improves surgical outcomes by identifying occult tumors and close surgical margins.
Topics: Humans; Margins of Excision; Lung; Lung Neoplasms; Molecular Imaging
PubMed: 37019717
DOI: 10.1016/j.jtcvs.2023.02.025 -
Clinics in Chest Medicine Jun 2024Early detection with accurate classification of solid pulmonary nodules is critical in reducing lung cancer morbidity and mortality. Computed tomography (CT) remains the... (Review)
Review
Early detection with accurate classification of solid pulmonary nodules is critical in reducing lung cancer morbidity and mortality. Computed tomography (CT) remains the most widely used imaging examination for pulmonary nodule evaluation; however, other imaging modalities, such as PET/CT and MRI, are increasingly used for nodule characterization. Current advances in solid nodule imaging are largely due to developments in machine learning, including automated nodule segmentation and computer-aided detection. This review explores current multi-modality solid pulmonary nodule detection and characterization with discussion of radiomics and risk prediction models.
Topics: Humans; Lung Neoplasms; Solitary Pulmonary Nodule; Tomography, X-Ray Computed; Positron Emission Tomography Computed Tomography; Magnetic Resonance Imaging; Multiple Pulmonary Nodules; Early Detection of Cancer
PubMed: 38816086
DOI: 10.1016/j.ccm.2023.08.013 -
Expert Review of Respiratory Medicine 2024Lung nodules are commonly encountered in clinical practice. Technological advances in navigational bronchoscopy and imaging modalities have led to paradigm shift from... (Review)
Review
INTRODUCTION
Lung nodules are commonly encountered in clinical practice. Technological advances in navigational bronchoscopy and imaging modalities have led to paradigm shift from nodule screening or follow-up to early lung cancer detection. This is due to improved nodule localization and biopsy confirmation with combined modalities of navigational platforms and imaging tools. To conduct this article, relevant literature was reviewed via PubMed from January 2014 until January 2024.
AREAS COVERED
This article highlights the literature on different imaging modalities combined with commonly used navigational platforms for diagnosis of peripheral lung nodules. Current limitations and future perspectives of imaging modalities will be discussed.
EXPERT OPINION
The development of navigational platforms improved localization of targets. However, published diagnostic yield remains lower compared to percutaneous-guided biopsy. The discordance between the actual location of lung nodule during the procedure and preprocedural CT chest is the main factor impacting accurate biopsies. The utilization of advanced imaging tools with navigation-based bronchoscopy has been shown to assist with localizing targets in real-time and improving biopsy success. However, it is important for interventional bronchoscopists to understand the strengths and limitations of these advanced imaging technologies.
Topics: Humans; Bronchoscopy; Lung Neoplasms; Image-Guided Biopsy; Solitary Pulmonary Nodule; Tomography, X-Ray Computed
PubMed: 38794918
DOI: 10.1080/17476348.2024.2359601