Integrating genomic features for non-invasive early lung cancer detection.

Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.

Risk model-based management for second primary lung cancer among lung cancer survivors through a validated risk prediction model.

BACKGROUND: Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk-prediction model (called SPLC-RAT) was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. The predictive performance of SPLC-RAT was evaluated in a hospital-based cohort of lung cancer survivors. METHODS: The authors analyzed data from 8448 ever-smoking patients diagnosed with initial primary lung cancer (IPLC) in 1997-2006 at Mayo Clinic, with each patient followed for SPLC through 2018. The predictive performance of SPLC-RAT and further explored the potential of improving SPLC detection through risk model-based surveillance using SPLC-RAT versus existing clinical surveillance guidelines. RESULTS: Of 8448 IPLC patients, 483 (5.7%) developed SPLC over 26,470 person-years. The application of SPLC-RAT showed high discrimination area under the receiver operating characteristics curve: 0.81). When the cohort was stratified by a 10-year risk threshold of ≥5.6% (i.e., 80th percentile from the SPLC-RAT development cohort), the observed SPLC incidence was significantly elevated in the high-risk versus low-risk subgroup (13.1% vs. 1.1%, p < 1 × 10-6 ). The risk-based surveillance through SPLC-RAT (≥5.6% threshold) outperformed the National Comprehensive Cancer Network guidelines with higher sensitivity (86.4% vs. 79.4%) and specificity (38.9% vs. 30.4%) and required 20% fewer computed tomography follow-ups needed to detect one SPLC (162 vs. 202). CONCLUSION: In a large, hospital-based cohort, the authors validated the predictive performance of SPLC-RAT in identifying high-risk survivors of SPLC and showed its potential to improve SPLC detection through risk-based surveillance. PLAIN LANGUAGE SUMMARY: Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC). However, no evidence-based guidelines for SPLC surveillance are available for lung cancer survivors. Recently, an SPLC risk-prediction model was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. Using a large, real-world cohort of lung cancer survivors, we showed the high predictive accuracy and risk-stratification ability of the SPLC risk-prediction model. Furthermore, we demonstrated the potential to enhance efficiency in detecting SPLC using risk model-based surveillance strategies compared to the existing consensus-based clinical guidelines, including the National Comprehensive Cancer Network.

Fleischner Society: Glossary of Terms for Thoracic Imaging.

Members of the Fleischner Society have compiled a glossary of terms for thoracic imaging that replaces previous glossaries published in 1984, 1996, and 2008, respectively. The impetus to update the previous version arose from multiple considerations. These include an awareness that new terms and concepts have emerged, others have become obsolete, and the usage of some terms has either changed or become inconsistent to a degree that warranted a new definition. This latest glossary is focused on terms of clinical importance and on those whose meaning may be perceived as vague or ambiguous. As with previous versions, the aim of the present glossary is to establish standardization of terminology for thoracic radiology and, thereby, to facilitate communications between radiologists and clinicians. Moreover, the present glossary aims to contribute to a more stringent use of terminology, increasingly required for structured reporting and accurate searches in large databases. Compared with the previous version, the number of images (chest radiography and CT) in the current version has substantially increased. The authors hope that this will enhance its educational and practical value. All definitions and images are hyperlinked throughout the text. Click on each figure callout to view corresponding image. © RSNA, 2024 Supplemental material is available for this article. See also the editorials by Bhalla and Powell in this issue.

Volumetric Analysis: Effect on Diagnosis and Management of Indeterminate Solid Pulmonary Nodules in Routine Clinical Practice.

OBJECTIVE: To evaluate the effect of volumetric analysis on the diagnosis and management of indeterminate solid pulmonary nodules in routine clinical practice. METHODS: This was a retrospective study with 107 computed tomography (CT) cases of solid pulmonary nodules (range, 6-15 mm), 57 pathology-proven malignancies (lung cancer, n = 34; metastasis, n = 23), and 50 benign nodules. Nodules were evaluated on a total of 309 CT scans (average number of CTs/nodule, 2.9 [range, 2-7]). CT scans were from multiple institutions with variable technique. Nine radiologists (attendings, n = 3; fellows, n = 3; residents, n = 3) were asked their level of suspicion for malignancy (low/moderate or high) and management recommendation (no follow-up, CT follow-up, or care escalation) for baseline and follow-up studies first without and then with volumetric analysis data. Effect of volumetry on diagnosis and management was assessed by generalized linear and logistic regression models. RESULTS: Volumetric analysis improved sensitivity (P = 0.009) and allowed earlier recognition (P < 0.05) of malignant nodules. Attending radiologists showed higher sensitivity in recognition of malignant nodules (P = 0.03) and recommendation of care escalation (P < 0.001) compared with trainees. Volumetric analysis altered management of high suspicion nodules only in the fellow group (P = 0.008). κ Statistics for suspicion for malignancy and recommended management were fair to substantial (0.38-0.66) and fair to moderate (0.33-0.50). Volumetric analysis improved interobserver variability for identification of nodule malignancy from 0.52 to 0.66 (P = 0.004) only on the second follow-up study. CONCLUSIONS: Volumetric analysis of indeterminate solid pulmonary nodules in routine clinical practice can result in improved sensitivity and earlier identification of malignant nodules. The effect of volumetric analysis on management recommendations is variable and influenced by reader experience.

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2022.

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Performance of a rule-based semi-automated method to optimize chart abstraction for surveillance imaging among patients treated for non-small cell lung cancer.

BACKGROUND: We aim to develop and test performance of a semi-automated method (computerized query combined with manual review) for chart abstraction in the identification and characterization of surveillance radiology imaging for post-treatment non-small cell lung cancer patients. METHODS: A gold standard dataset consisting of 3011 radiology reports from 361 lung cancer patients treated at the Veterans Health Administration from 2008 to 2016 was manually created by an abstractor coding image type, image indication, and image findings. Computerized queries using a text search tool were performed to code reports. The primary endpoint of query performance was evaluated by sensitivity, positive predictive value (PPV), and F1 score. The secondary endpoint of efficiency compared semi-automated abstraction time to manual abstraction time using a separate dataset and the Wilcoxon rank-sum test. RESULTS: Query for image type demonstrated the highest sensitivity of 85%, PPV 95%, and F1 score 0.90. Query for image indication demonstrated sensitivity 72%, PPV 70%, and F1 score 0.71. The image findings queries ranged from sensitivity 75-85%, PPV 23-25%, and F1 score 0.36-0.37. Semi-automated abstraction with our best performing query (image type) improved abstraction times by 68% per patient compared to manual abstraction alone (from median 21.5 min (interquartile range 16.0) to 6.9 min (interquartile range 9.5), p < 0.005). CONCLUSIONS: Semi-automated abstraction using the best performing query of image type improved abstraction efficiency while preserving data accuracy. The computerized query acts as a pre-processing tool for manual abstraction by restricting effort to relevant images. Determining image indication and findings requires the addition of manual review for a semi-automatic abstraction approach in order to ensure data accuracy.

A risk-based framework for assessing real-time lung cancer screening eligibility that incorporates life expectancy and past screening findings.

BACKGROUND: Current lung cancer risk-based screening approaches use a single risk-threshold, disregard life-expectancy, and ignore past screening findings. We address these limitations with a comprehensive analytical framework, the individualized lung cancer screening decision (ENGAGE) tool that aims to optimize lung cancer screening for US ever-smokers under dynamic risk assessment by incorporating life expectancy and past screening findings over time. METHODS: ENGAGE employs a partially observable Markov decision process framework that integrates published risk prediction and disease progression models, to dynamically assess the trade-off between the expected health benefits and harms associated with screening. ENGAGE evaluates lung cancer risk annually and provides real-time screening eligibility that maximizes the expected quality-adjusted life-years (QALYs) of ever-smokers. We compare ENGAGE against the 2013 U.S. Preventive Services Task Force (USPSTF) lung cancer screening guideline and single-threshold risk-based screening paradigms. RESULTS: Compared with the 2013 USPSTF guidelines, ENGAGE expands screening coverage among ever-smokers (ENGAGE: 78%, USPSTF: 61%), while reducing the number of screening examinations per person (ENGAGE:10.43, USPSTF:12.07, P < .001), yields higher effectiveness in terms of increased lung cancer-specific mortality reduction (ENGAGE: 19%, USPSTF: 15%, P < .001) and improves screening efficiency (ENGAGE: 696, USPSTF: 819 screens per death avoided, P < .001). When compared against a single-threshold risk-based screening strategy, ENGAGE increases QALY requiring 30% fewer screens per death avoided (ENGAGE: 696, single-threshold: 889, P < .001), and reduces false positives by 40%. CONCLUSIONS: ENGAGE provides a comprehensive framework for dynamic risk-based assessment of lung cancer screening eligibility by incorporating life expectancy and past screening findings that can serve to guide future policies on the effectiveness and efficiency of screening. LAY SUMMARY: A novel decision-analytical screening framework was developed for lung cancer, the individualized lung cancer screening decision (ENGAGE) tool to provide personalized screening schedules for ever-smokers. ENGAGE captures the dynamic nature of lung cancer risk and incorporates life expectancy into the screening decision-making process. ENGAGE integrates past screening findings and changes in smoking behavior of individuals and provides informed screening decisions that outperform existing screening guidelines and single-threshold risk-based screening approaches. A personalized lung cancer screening program facilitated by a tool such as ENGAGE could enhance the efficiency of lung cancer screening.

Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial.

BACKGROUND: Ixekizumab, a high-affinity interleukin-17A (IL-17A) monoclonal antibody, has previously shown efficacy in radiographic axial spondyloarthritis (also known as ankylosing spondylitis). We aimed to evaluate the efficacy and safety of ixekizumab, an IL-17 inhibitor, in non-radiographic axial spondyloarthritis. Here, we report the primary results of COAST-X. METHODS: COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomly assigned (1:1:1) to receive subcutaneous 80 mg ixekizumab every 4 weeks (Q4W) or every 2 weeks (Q2W), or placebo. Changing background medications or switching to open-label ixekizumab Q2W, or both, was allowed after week 16 at investigator discretion. Primary endpoints were Assessment of SpondyloArthritis international Society-40 (ASAS40) response (defined as an improvement of 40% or more and an absolute improvement from baseline of 2 units or more [range 0-10] in at least three of the four domains [patient global, spinal pain, function, and inflammation] without any worsening in the remaining one domain) at weeks 16 and 52. Patients who switched to open-label ixekizumab were imputed as non-responders in logistic regression analysis. This trial is registered with ClinicalTrials.gov, number NCT02757352. FINDINGS: Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled (105 to placebo, 96 to ixekizumab Q4W, and 102 to ixekizumab Q2W). Both primary endpoints were met: ASAS40 at week 16 (ixekizumab Q4W: 34 [35%] of 96, p=0·0094 vs placebo; ixekizumab Q2W: 41 [40%] of 102, p=0·0016; placebo: 20 [19%] of 105) and ASAS40 at week 52 (ixekizumab Q4W: 29 [30%] of 96, p=0·0045; ixekizumab Q2W: 32 [31%] of 102, p=0·0037; placebo: 14 [13%] of 105). 60 (57%) of 104 patients in the placebo group, 63 (66%) of 96 in the ixekizumab Q4W group, and 79 (77%) of 102 in the ixekizumab Q2W group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events in the ixekizumab groups were nasopharyngitis and injection site reaction. Of the treatment-emergent adverse events of special interest, there was one case of serious infection in the ixekizumab Q4W group. The frequency of serious adverse events was low (four [1%] of 302) and similar across the three groups. There were no malignancies or deaths. No new safety signals were identified. INTERPRETATION: Ixekizumab was superior to placebo for improving signs and symptoms in patients with non-radiographic axial spondyloarthritis at weeks 16 and 52. Reports of adverse events were similar to those of previous ixekizumab studies. Ixekizumab offers a potential therapeutic option for patients with non-radiographic axial spondyloarthritis who had an inadequate response or were intolerant to NSAID therapy. FUNDING: Eli Lilly and Company.

Imaging of Pulmonary Hypertension in Adults: A Position Paper from the Fleischner Society.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mm Hg and classified into five different groups sharing similar pathophysiologic mechanisms, hemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: (a) Is noninvasive imaging capable of identifying PH? (b) What is the role of imaging in establishing the cause of PH? (c) How does imaging determine the severity and complications of PH? (d) How should imaging be used to assess chronic thromboembolic PH before treatment? (e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH. This article is a simultaneous joint publication in Radiology and European Respiratory Journal. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. © 2021 RSNA and the European Respiratory Society. Online supplemental material is available for this article.

Imaging of pulmonary hypertension in adults: a position paper from the Fleischner Society.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mmHg and classified into five different groups sharing similar pathophysiologic mechanisms, haemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: a) Is noninvasive imaging capable of identifying PH? b) What is the role of imaging in establishing the cause of PH? c) How does imaging determine the severity and complications of PH? d) How should imaging be used to assess chronic thromboembolic PH before treatment? e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH.

Long-term efficacy and safety of ixekizumab: A 5-year analysis of the UNCOVER-3 randomized controlled trial.

OBJECTIVE: To report the efficacy and safety of the approved ixekizumab (IXE) dose over 5 years from UNCOVER-3 (NCT01646177). METHODS: Patients (N = 1346) were randomized 1:2:2:2 to receive subcutaneous injections of placebo, etanercept 50 mg twice weekly, or IXE 80 mg every 2 weeks or every 4 weeks after an initial dose of IXE 160 mg, respectively. At week 12, patients entered the long-term extension period with dosing of IXE every 4 weeks and could escalate to every 2 weeks after week 60. Efficacy was reported for the IXE every 2 weeks/every 4 weeks group of the intent-to-treat population. Safety was reported for patients who received at least 1 dose of IXE every 2 or every 4 weeks. RESULTS: Using modified nonresponder imputation, 78.8%/67.1%/46.2% of patients receiving the approved dose of IXE every 2 weeks/every 4 weeks (n = 385) achieved ≥75%, ≥90%, or 100% improvement from baseline in the Psoriasis Area and Severity Index, respectively, at week 264; static Physician's Global Assessment score of 0/1 and 0 responses were 69.2% and 45.3%, respectively. Infections were the most observed treatment-emergent adverse event (72.7% of patients). LIMITATIONS: Lack of comparison treatment group after week 12. CONCLUSION: IXE demonstrates sustained efficacy and consistent safety through 264 weeks in patients using the approved dose.

Multi-institution consensus paper for acquisition of portable chest radiographs through glass barriers.

BACKGROUND: To conserve personal protective equipment (PPE) and reduce exposure to potentially infected COVID-19 patients, several Californian facilities independently implemented a method of acquiring portable chest radiographs through glass barriers that was originally developed by the University of Washington. METHODS: This work quantifies the transmission of radiation through a glass barrier using six radiographic systems at five facilities. Patient entrance air kerma (EAK) and effective dose were estimated both with and without the glass barrier. Beam penetrability and resulting exposure index (EI) and deviation index (DI) were measured and used to adjust the tube current-time product (mAs) for glass barriers. Because of beam hardening, the contrast-to-noise ratio (CNR) was measured with image quality phantoms to ensure diagnostic integrity. Finally, scatter surveys were performed to assess staff radiation exposure both inside and outside the exam room. RESULTS: The glass barriers attenuated a mean of 61% of the normal X-ray beams. When the mAs was increased to match EI values, there was no discernible degradation of image quality as determined by the CNR. This was corroborated with subjective assessments of image quality by chest radiologists. The glass-hardened beams acted as a filter for low energy X-rays, and some facilities observed slight changes in patient effective doses. There was scattering from both the phantoms and the glass barriers within the room. CONCLUSIONS: Glass barriers require an approximate 2.5 times increase in beam intensity, with all other technique factors held constant. Further refinements are necessary for increased source-to-image distance and beam quality in order to adequately match EI values. This does not result in a significant increase in the radiation dose delivered to the patient. The use of lead aprons, mobile shields, and increased distance from scattering sources should be employed where practicable in order to keep staff radiation doses as low as reasonably achievable.

The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society.

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.

Bone Marrow and Tumor Radiomics at 18F-FDG PET/CT: Impact on Outcome Prediction in Non-Small Cell Lung Cancer.

Background Primary tumor maximum standardized uptake value is a prognostic marker for non-small cell lung cancer. In the setting of malignancy, bone marrow activity from fluorine 18-fluorodeoxyglucose (FDG) PET may be informative for clinical risk stratification. Purpose To determine whether integrating FDG PET radiomic features of the primary tumor, tumor penumbra, and bone marrow identifies lung cancer disease-free survival more accurately than clinical features alone. Materials and Methods Patients were retrospectively analyzed from two distinct cohorts collected between 2008 and 2016. Each tumor, its surrounding penumbra, and bone marrow from the L3-L5 vertebral bodies was contoured on pretreatment FDG PET/CT images. There were 156 bone marrow and 512 tumor and penumbra radiomic features computed from the PET series. Randomized sparse Cox regression by least absolute shrinkage and selection operator identified features that predicted disease-free survival in the training cohort. Cox proportional hazards models were built and locked in the training cohort, then evaluated in an independent cohort for temporal validation. Results There were 227 patients analyzed; 136 for training (mean age, 69 years ± 9 [standard deviation]; 101 men) and 91 for temporal validation (mean age, 72 years ± 10; 91 men). The top clinical model included stage; adding tumor region features alone improved outcome prediction (log likelihood, -158 vs -152; P = .007). Adding bone marrow features continued to improve performance (log likelihood, -158 vs -145; P = .001). The top model integrated stage, two bone marrow texture features, one tumor with penumbra texture feature, and two penumbra texture features (concordance, 0.78; 95% confidence interval: 0.70, 0.85; P < .001). This fully integrated model was a predictor of poor outcome in the independent cohort (concordance, 0.72; 95% confidence interval: 0.64, 0.80; P < .001) and a binary score stratified patients into high and low risk of poor outcome (P < .001). Conclusion A model that includes pretreatment fluorine 18-fluorodeoxyglucose PET texture features from the primary tumor, tumor penumbra, and bone marrow predicts disease-free survival of patients with non-small cell lung cancer more accurately than clinical features alone. © RSNA, 2019 Online supplemental material is available for this article.

Emergent high fatality lung disease in systemic juvenile arthritis.

OBJECTIVE: To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA). METHODS: In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data. RESULTS: LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features. CONCLUSIONS: A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

Non-Small Cell Lung Cancer Radiogenomics Map Identifies Relationships between Molecular and Imaging Phenotypes with Prognostic Implications.

Purpose To create a radiogenomic map linking computed tomographic (CT) image features and gene expression profiles generated by RNA sequencing for patients with non-small cell lung cancer (NSCLC). Materials and Methods A cohort of 113 patients with NSCLC diagnosed between April 2008 and September 2014 who had preoperative CT data and tumor tissue available was studied. For each tumor, a thoracic radiologist recorded 87 semantic image features, selected to reflect radiologic characteristics of nodule shape, margin, texture, tumor environment, and overall lung characteristics. Next, total RNA was extracted from the tissue and analyzed with RNA sequencing technology. Ten highly coexpressed gene clusters, termed metagenes, were identified, validated in publicly available gene-expression cohorts, and correlated with prognosis. Next, a radiogenomics map was built that linked semantic image features to metagenes by using the t statistic and the Spearman correlation metric with multiple testing correction. Results RNA sequencing analysis resulted in 10 metagenes that capture a variety of molecular pathways, including the epidermal growth factor (EGF) pathway. A radiogenomic map was created with 32 statistically significant correlations between semantic image features and metagenes. For example, nodule attenuation and margins are associated with the late cell-cycle genes, and a metagene that represents the EGF pathway was significantly correlated with the presence of ground-glass opacity and irregular nodules or nodules with poorly defined margins. Conclusion Radiogenomic analysis of NSCLC showed multiple associations between semantic image features and metagenes that represented canonical molecular pathways, and it can result in noninvasive identification of molecular properties of NSCLC. Online supplemental material is available for this article.

Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.

Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer. Lung screening is covered under the Affordable Care Act for individuals with high-risk factors. The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer if they also receive counseling and participate in shared decision-making before screening. The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening. This manuscript focuses on identifying patients at high risk for lung cancer who are candidates for LDCT of the chest and on evaluating initial screening findings.

An Analysis of Lung Cancer Screening Beliefs and Practice Patterns for Community Providers Compared to Academic Providers.

Despite guidelines recommending annual low-dose computed tomography (LDCT) screening for lung cancer, uptake remains low due to the perceived complexity of initiating and maintaining a clinical program-problems that likely magnify in underserved populations. We conducted a survey of community providers at Federally Qualified Health Centers (FQHCs) in Santa Clara County, California, to evaluate provider-related factors that affect adherence. We then compared these findings to academic providers' (APs) LDCT screening knowledge, behaviors, and attitudes at an academic referral center in the same county. The 4 FQHCs enrolled care for 80 000 patients largely of minority descent and insured by Medi-Cal. Of the 75 FQHC providers (FQHCPs), 36 (48%) completed the survey. Of the 36 providers, 8 (22%) knew screening criteria. Fifteen (42%) FQHCPs discussed LDCT screening with patients. Compared to 36 APs, FQHCPs were more concerned about harms, false positives, discussion time, patient apathy, insurance coverage, and a lack of expertise for screening and follow-up. Yet, more FQHCPs thought screening was effective (27 [75%] of 36) compared to APs ( P = .0003). In conclusion, provider knowledge gaps are greater and barriers are different for community clinics caring for underserved populations compared to their academic counterparts, but practical and scalable solutions exist to enhance adoption.

Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017.

The Fleischner Society Guidelines for management of solid nodules were published in 2005, and separate guidelines for subsolid nodules were issued in 2013. Since then, new information has become available; therefore, the guidelines have been revised to reflect current thinking on nodule management. The revised guidelines incorporate several substantive changes that reflect current thinking on the management of small nodules. The minimum threshold size for routine follow-up has been increased, and recommended follow-up intervals are now given as a range rather than as a precise time period to give radiologists, clinicians, and patients greater discretion to accommodate individual risk factors and preferences. The guidelines for solid and subsolid nodules have been combined in one simplified table, and specific recommendations have been included for multiple nodules. These guidelines represent the consensus of the Fleischner Society, and as such, they incorporate the opinions of a multidisciplinary international group of thoracic radiologists, pulmonologists, surgeons, pathologists, and other specialists. Changes from the previous guidelines issued by the Fleischner Society are based on new data and accumulated experience. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 13, 2017.