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Rationale: Although interstitial lung abnormalities (ILA), specific patterns of incidentally-detected abnormal density on computed tomography, have been associated with abnormal lung function and increased mortality, it is unclear if a subset with incidental interstitial lung disease (ILD) accounts for these adverse consequences. Objectives: To define the prevalence and risk factors of suspected ILD and assess outcomes. Methods: Suspected ILD was evaluated in the COPDGene (Chronic Obstructive Pulmonary Disease Genetic Epidemiology) study, defined as ILA and at least one additional criterion: definite fibrosis on computed tomography, FVC less than 80% predicted, or DL CO less than 70% predicted. Multivariable linear, longitudinal, and Cox proportional hazards regression models were used to assess associations with St. George's Respiratory Questionnaire, 6-minute-walk test, supplemental oxygen use, respiratory exacerbations, and mortality. Measurements and Main Results: Of 4,361 participants with available data, 239 (5%) had evidence for suspected ILD, whereas 204 (5%) had ILA without suspected ILD. In multivariable analyses, suspected ILD was associated with increased St. George's Respiratory Questionnaire score (mean difference [MD], 3.9 points; 95% confidence interval [CI], 0.6-7.1; P  = 0.02), reduced 6-minute-walk test (MD, -35 m; 95% CI, -56 m to -13 m; P  = 0.002), greater supplemental oxygen use (odds ratio [OR], 2.3; 95% CI, 1.1-5.1; P  = 0.03) and severe respiratory exacerbations (OR, 2.9; 95% CI, 1.1-7.5; P  = 0.03), and higher mortality (hazard ratio, 2.4; 95% CI, 1.2-4.6; P  = 0.01) compared with ILA without suspected ILD. Risk factors associated with suspected ILD included self-identified Black race (OR, 2.0; 95% CI, 1.1-3.3; P  = 0.01) and pack-years smoking history (OR, 1.2; 95% CI, 1.1-1.3; P  = 0.0005). Conclusions: Suspected ILD is present in half of those with ILA in COPDGene and is associated with exercise decrements and increased symptoms, supplemental oxygen use, severe respiratory exacerbations, and mortality.

Small cell lung cancer (SCLC) is a highly aggressive malignancy with exceptionally poor prognosis, comprising approximately 15% of lung cancers. Emerging knowledge of the molecular and genomic landscape of SCLC and recent successful clinical applications of new systemic agents have allowed for precision oncology treatment approaches. Imaging is essential for the diagnosis, staging, and treatment monitoring of patients with SCLC. The role of imaging is increasing with the approval of new treatment agents, including immune checkpoint inhibitors, which lead to novel imaging manifestations of response and toxicities. The purpose of this state-of-the-art review is to provide the reader with the latest information about SCLC, focusing on the subtyping of this malignancy (molecular characterization) and the emerging systemic therapeutic approaches and their implications for imaging. The review will also discuss the future directions of SCLC imaging, radiomics and machine learning., (© RSNA, 2022.)

Objectives: To assess the association of projected lung area (PLA) measured by DXR with demographic data, pulmonary function, and COPD severity, and to generate PLA over time curves using automated tracking., Methods: This retrospective study recruited healthy volunteers and COPD patients. Participants were classified into three groups: normal, COPD mild and COPD severe. PLA was calculated from the manually traced bilateral lung contours. PLA over time curves were produced using automated tracking, which was used to calculate slope and intercept by approximate line during forced expiration. The correlation of PLA, difference of PLA between end-inspiration and end-expiration (ΔPLA), slope, and intercept with demographic data and pulmonary function tests were investigated. The difference of PLA, ΔPLA, intercept, and slope among three groups were also evaluated., Results: This study enrolled 45 healthy volunteers and 32 COPD patients. COPD severe group had larger PLA in both lungs at tidal/forced end-inspiration/expiration, smaller slope, and larger intercept than normal group (p < 0.001). PLA was correlated with % forced expiratory volume in one second (%FEV 1 ) (r s from -0.42 to -0.31, p ≤ 0.01). ΔPLA in forced breathing showed moderate correlation with vital capacity (VC) (r s  = 0.58, p < 0.001), while ΔPLA in tidal breathing showed moderate correlation with %FEV 1 (r s  = -0.52, p < 0.001) as well as mild correlation with tidal volume (r s  = 0.24, p = 0.032). Intercept was slightly underestimated compared with manually contoured PLA (p < 0.001)., Conclusion: COPD patients had larger PLA than healthy volunteers. PLA and ΔPLA in tidal breathing showed mild to moderate correlation with %FEV 1 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: To investigate the effect of vaccinations and boosters on the severity of COVID-19 pneumonia on CT scans during the period of Delta and Omicron variants., Methods: Retrospectively studied were 303 patients diagnosed with COVID-19 between July 2021 and February 2022, who had obtained at least one CT scan within 6 weeks around the COVID-19 diagnosis (-2 to +4 weeks). The severity of pneumonia was evaluated with a 6-point scale Pneumonia Score. The association between demographic and clinical data and vaccination status (booster/additional vaccination, complete vaccination and un-vaccination) and the difference between Pneumonia Scores by vaccination status were investigated., Results: Of 303 patients (59.4 ± 16.3 years; 178 females), 62 (20 %) were in the booster/additional vaccination group, 117 (39 %) in the complete vaccination group, and 124 (41 %) in the unvaccinated group. Interobserver agreement of the Pneumonia Score was high (weighted kappa score = 0.875). Patients in the booster/additionally vaccinated group tended to be older (P = 0.0085) and have more underlying comorbidities (P < 0.0001), and the Pneumonia Scores were lower in the booster/additionally vaccinated [median 2 (IQR 0-4)] and completely vaccinated groups [median 3 (IQR 1-4)] than those in the unvaccinated group [median 4 (IQR 2-4)], respectively (P < 0.0001 and P < 0.0001, respectively). A multivariable linear analysis adjusted for confounding factors confirmed the difference., Conclusion: Vaccinated patients, with or without booster/additional vaccination, had milder COVID-19 pneumonia on CT scans than unvaccinated patients during the period of Delta and Omicron variants. This study supports the efficacy of the vaccine against COVID-19 from a radiological perspective., Competing Interests: M.N. reports research grant to the institution from Merck, Canon Medical Systems, AstraZeneca, and Daiichi Sankyo; and consulting fees from Daiichi Sankyo and AstraZeneca, outside the submitted work. C.R.G.G. reports stock ownership of GSK, Roche, and Novartis, outside the submitted work. G.M.H. reports consulting fees from Boehringer Ingelheim, Gerson Lehrman Group, and Chugai Pharmaceuticals, outside the submitted work. B.D.L reports grants or contacts from NIH, Pieris Pharmaceuticals, SRA, and Sanofi; royalties or licenses from Propeller Health; consulting fees from AstraZeneca, NControl, Cartesian, Novartis, Gossamer Bio, and Thetis Pharmaceuticals; participation on a data safety monitoring board or advisory board from NIAID; and stock or stock options from Entrinsic Biosciences and Nocion Therapeutics, outside the submitted work. H.H. reports grants or contracts from Canon Medical Systems Inc and Konica-Minolta Inc; and consulting fees from Canon Medical Systems Inc and Mitsubishi Chemical Co, outside the submitted work. The other authors have no conflicts of interest to be disclosed related to this article., (© 2022 The Authors.)

Purpose: Interstitial lung abnormalities (ILAs) represent nondependent abnormalities on chest computed tomography (CT) indicating lung parenchymal damages due to inflammation and fibrosis. Interstitial lung abnormalities have been studied as a predictor of clinical outcome in lung cancer, but not in other thoracic malignancies. The present study investigated the prevalence of ILA in patients with esophageal cancer and identified risk factors and clinical implications of ILA in these patients., Methods: The study included 208 patients with locally advanced esophageal cancer (median age, 65.6 years; 166 males, 42 females). Interstitial lung abnormality was scored on baseline CT scans before treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA). Clinical characteristics and overall survival were compared in patients with ILA (score 2) and others., Results: An ILA was present in 14 of 208 patients (7%) with esophageal cancer on pretreatment chest CT. Patients with ILA were significantly older (median age, 69 vs 65, respectively; P = 0.011), had a higher number of pack-years of smoking ( P = 0.02), and more commonly had T4 stage disease ( P = 0.026) than patients with ILA score of 1 or 0. Interstitial lung abnormality on baseline scan was associated with a lack of surgical resection after chemoradiotherapy (7/14, 50% vs 39/194, 20% respectively; P = 0.016). Interstitial lung abnormality was not associated with overall survival (log-rank P = 0.75, Cox P = 0.613)., Conclusions: An ILA was present in 7% of esophageal cancer patients, which is similar to the prevalence in general population and in smokers. Interstitial lung abnormality was strongly associated with a lack of surgical resection after chemoradiotherapy, indicating an implication of ILA in treatment selection in these patients, which can be further studied in larger cohorts., Competing Interests: The authors declare no supported by R01CA203636, U01CA209414, R01HL111024, and R01CA240592. H.H. received research funding from Canon, Inc, Canon Medical Systems, and Konica-Minolta; Consultant to Canon Medical Systems, and Mitsubishi Chemical, Inc. M.N. served as a consultant to Daiichi Sankyo and AstraZeneca and received research grant from Merck, Canon Medical Systems, AstraZeneca, and Daiichi Sankyo. HM does consulting for Merck and received royalties from UpToDate. The other authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Interstitial lung abnormality (ILA) is defined as an interstitial change detected incidentally on CT images. It is seen in 4%-9% of smokers and 2%-7% of nonsmokers. ILA has a tendency to progress with time and is associated with respiratory symptoms, decreased exercise capability, reduced pulmonary function, and increased mortality. ILAs can be classified into three subcategories: nonsubpleural, subpleural nonfibrotic, and subpleural fibrotic. In cases of ILA, clinically significant interstitial lung disease should be identified and requires clinically driven management by a pulmonologist. Risk factors for the progression of ILA include clinical elements (ie, inhalation exposures, medication use, radiation therapy, thoracic surgery, physiologic findings, and gas exchange findings) and radiologic elements (ie, basal and peripheral predominance and fibrotic findings). It is recommended that individuals with one or more clinical or radiologic risk factors for progression of ILA be actively monitored with pulmonary function testing and CT. To avoid overcalling ILA at CT, radiologists must recognize the imaging pitfalls, including centrilobular nodularity, dependent abnormality, suboptimal inspiration, osteophyte-related lesions, apical cap and pleuroparenchymal fibroelastosis-like lesions, aspiration, and infection. There is a close association between ILA and lung cancer, and many studies have reported an increased incidence of lung cancer, worse prognoses, and/or increased pulmonary complications in relation to cancer treatment in patients with ILA. ILA is considered to be an important comorbidity in patients with lung cancer. Accordingly, all radiologists involved with body CT must have sound knowledge of ILAs owing to the high prevalence and potential clinical significance of these anomalies. An overview of ILAs, including a literature review of the associations between ILAs and lung cancer, is presented. © RSNA, 2022.

Although interstitial lung disease (ILD) causes significant morbidity and mortality in rheumatoid arthritis (RA), it is difficult to predict the development or progression of ILD, emphasising the need for improved discovery through minimally invasive diagnostic tests. Aptamer-based proteomic profiling was used to assess 1321 proteins from 159 patients with rheumatoid arthritis with interstitial lung disease (RA-ILD), RA without ILD, idiopathic pulmonary fibrosis and healthy controls. Differential expression and gene set enrichment analyses revealed molecular signatures that are strongly associated with the presence and severity of RA-ILD and provided insight into unexplored pathways of disease. These warrant further study as non-invasive diagnostic tools and future therapeutic targets., Competing Interests: Competing interests: The authors have reported the following conflicts of interest, all outside the submitted work: ST reports medical advisory group membership of Novo Nordisk and board membership at Droobi Health, Qatar. RG receives grant support from Canon Medical Systems. HH reports grants from Canon Medical Systems and Konica Minolta, and personal fees from Mitsubishi Chemical Co and Canon Medical Systems Inc. MN reports grants from AstraZeneca, Daiichi Sankyo, Canon Medical Systems, Merck investigator studies program; personal fees from Daiichi Sankyo and AstraZeneca. MEW receives research support from Amgen, Bristol Myers Squibb and Eli Lilly and consultation fees from AbbVie, Aclaris, Amgen, Arena, Bayer, Bristol Myers Squibb, Corvitas, Eqrx, Genosco, GSK, Gilead, Horizon, Johnson & Johnson, Kiniksa, Lilly, Novartis, Pfizer, Rami Therapeutics, R Pharma, Roche, Sanofi, Scipher, Sci Rhom, Set Point and Tremeau. He holds stock/stock options of CanFite, Inmedix, Vorso and Scipher. NAS reports grants and other support from Bristol-Myers Squibb, grants from Mallinckrodt, Sanofi, Crescendo Biosciences, Lilly and Amgen. PFD reports grants from Bristol-Myers Squibb and Genentech, and other support from Boehringer Ingelheim. AMKC is a cofounder and equity stock holder for Proterris, which develops therapeutic uses for carbon monoxide, and also has a use patent on CO and a patent in chronic obstructive pulmonary disease. EYK is a member of the steering committees for and receives no financial remuneration from NCT04409834 (Prevention of arteriovenous thrombotic events in critically ill COVID-19 patients, TIMI group) and REMAP-CAP ACE2 renin–angiotensin system modulation domain, and receives unrelated research funding from Bayer AG, Roche Pharma Research and Early Development, Windtree Therapeutics, the US National Institutes of Health, the US Agency for International Development, the American Heart Association, American Lung Association and the Bell Family Fund. IOR reports grants from Genentech. FJM reports personal fees, non-financial support and other support from AstraZeneca, other support from Afferent/Merck, personal fees, non-financial support and other support from Boehringer Ingelheim, other support from Bristol Myers Squibb, other support from Chiesi, personal fees and non-financial support from the Canadian Respiratory Society, personal fees and non-financial support from CME Outfitters, personal fees and non-financial support from CSL Behring, personal fees from Dartmouth University, personal fees from France Foundation, personal fees from Gala, personal fees and non-financial support from Genentech, grants, personal fees, non-financial support and other support from GlaxoSmithKline, personal fees and non-financial support from Inova Fairfax, personal fees and non-financial support from MD Magazine, personal fees and non-financial support from NYP Methodist Hospital Brooklyn, personal fees and non-financial support from Miller Communications, personal fees and non-financial support from National Association for Continuing Education/Integritas, other support from Nitto, personal fees and non-financial support from Novartis, personal fees from New York University, personal fees and non-financial support from Patara/Respivant, personal fees from Pearl, personal fees and non-financial support from Peer View, personal fees from Physicians Education Resource, personal fees from ProMedior, personal fees and non-financial support from Rare Diseases Healthcare Communications, personal fees from Rockpointe Communications, personal fees and non-financial support from Sanofi/Regeneron, other support from Biogen, personal fees and non-financial support from Sunovion, personal fees and non-financial support from Teva, other support from two XAR, personal fees from University of Birmingham Alabama, personal fees from UpToDate, non-financial support from Veracyte, personal fees from Vindico, personal fees and non-financial support from WebMD/MedScape, non-financial support and other support from Zambon, non-financial support from ProTerrix Bio, and personal fees from IQVIA, Raziel, Abvie and Verona. TJD has received grant support from Bristol Myers Squibb, consulting fees from Boehringer Ingelheim and L.E.K. consulting, and has been part of a clinical trial funded by Genentech. The remaining authors have reported no conflicts of interest., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background The clinical impact of interstitial lung abnormalities (ILAs) on poor prognosis has been reported in many studies, but risk stratification in ILA will contribute to clinical practice. Purpose To investigate the association of traction bronchiectasis/bronchiolectasis index (TBI) with mortality and clinical outcomes in individuals with ILA by using the COPDGene cohort. Materials and Methods This study was a secondary analysis of prospectively collected data. Chest CT scans of participants with ILA for traction bronchiectasis/bronchiolectasis were evaluated and outcomes were compared with participants without ILA from the COPDGene study (January 2008 to June 2011). TBI was classified as follows: TBI-0, ILA without traction bronchiectasis/bronchiolectasis; TBI-1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; TBI-2, ILA with mild to moderate traction bronchiectasis; and TBI-3, ILA with severe traction bronchiectasis and/or honeycombing. Clinical outcomes and overall survival were compared among the TBI groups and the non-ILA group by using multivariable linear regression model and Cox proportional hazards model, respectively. Results Overall, 5295 participants (median age, 59 years; IQR, 52-66 years; 2779 men) were included, and 582 participants with ILA and 4713 participants without ILA were identified. TBI groups were associated with poorer clinical outcomes such as quality of life scores in the multivariable linear regression model (TBI-0: coefficient, 3.2 [95% CI: 0.6, 5.7; P = .01]; TBI-1: coefficient, 3.3 [95% CI: 1.1, 5.6; P = .003]; TBI-2: coefficient, 7.6 [95% CI: 4.0, 11; P < .001]; TBI-3: coefficient, 32 [95% CI: 17, 48; P < .001]). The multivariable Cox model demonstrated that ILA without traction bronchiectasis (TBI-0-1) and with traction bronchiectasis (TBI-2-3) were associated with shorter overall survival (TBI-0-1: hazard ratio [HR], 1.4 [95% CI: 1.0, 1.9; P = .049]; TBI-2-3: HR, 3.8 [95% CI: 2.6, 5.6; P < .001]). Conclusion Traction bronchiectasis/bronchiolectasis was associated with poorer clinical outcomes compared with the group without interstitial lung abnormalities; TBI-2 and 3 were associated with shorter survival. © RSNA, 2022 Online supplemental material is available for this article . See also the editorial by Lee and Im in this issue.

Background: Interstitial lung abnormalities (ILA) share many features with idiopathic pulmonary fibrosis; however, it is not known if ILA are associated with decreased mean telomere length (MTL)., Methods: Telomere length was measured with quantitative PCR in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) and Age Gene/Environment Susceptibility Reykjavik (AGES-Reykjavik) cohorts and Southern blot analysis was used in the Framingham Heart Study (FHS). Logistic and linear regression were used to assess the association between ILA and MTL; Cox proportional hazards models were used to assess the association between MTL and mortality., Results: In all three cohorts, ILA were associated with decreased MTL. In the COPDGene and AGES-Reykjavik cohorts, after adjustment there was greater than twofold increase in the odds of ILA when comparing the shortest quartile of telomere length to the longest quartile (OR 2.2, 95% CI 1.5-3.4, p=0.0001, and OR 2.6, 95% CI 1.4-4.9, p=0.003, respectively). In the FHS, those with ILA had shorter telomeres than those without ILA (-767 bp, 95% CI 76-1584 bp, p=0.03). Although decreased MTL was associated with chronic obstructive pulmonary disease (OR 1.3, 95% CI 1.1-1.6, p=0.01) in COPDGene, the effect estimate was less than that noted with ILA. There was no consistent association between MTL and risk of death when comparing the shortest quartile of telomere length in COPDGene and AGES-Reykjavik (HR 0.82, 95% CI 0.4-1.7, p=0.6, and HR 1.2, 95% CI 0.6-2.2, p=0.5, respectively)., Conclusion: ILA are associated with decreased MTL., Competing Interests: Conflict of interest: R.K. Putman reports grants from NIH/NHLBI, during the conduct of the study. Conflict of interest: G.T. Axelsson has nothing to disclose. Conflict of interest: S.Y. Ash reports grants from NHLBI (K08HL145118) and Pulmonary Fibrosis Foundation, during the conduct of the study; and is the owner of Quantitative Imaging Solutions, outside the submitted work. Conflict of interest: J.L. Sanders has commenced employment at Vertex Pharmaceuticals Inc. since the study was completed. Conflict of interest: A.A. Menon has nothing to disclose. Conflict of interest: T. Araki has nothing to disclose. Conflict of interest: M. Nishino reports personal fees for consultancy from Daiichi Sankyo and AstraZeneca, and grants from the Merck investigator studies programme, Canon Medical Systems, AstraZeneca and Daiichi Sankyo, outside the submitted work. Conflict of interest: M. Yanagawa reports travel expenses from Canon Medical Systems, outside the submitted work. Conflict of interest: E.F. Gudmundsson has nothing to disclose. Conflict of interest: D. Qiao has nothing to disclose. Conflict of interest: R. San José Estépar reports grants from Boehringer Ingelheim, Lung Biotechnology and Insmed, payment for lectures and travel expenses from Chiesi, and stock and/or stock options from Quantitative Imaging Solutions, outside the submitted work. Conflict of interest: J. Dupuis reports grants from NIH, during the conduct of the study. Conflict of interest: G.T. O'Connor reports grants from NIH, during the conduct of the study. Conflict of interest: I.O. Rosas has a patent 62/849,644 pending. Conflict of interest: G.R. Washko reports grants from Boehringer Ingelheim, consultancy for Pulmonx, Janssen Pharmaceuticals, Novartis and Vertex, and is founder and co-owner of Quantitative Imaging Solutions, outside the submitted work. Conflict of interest: S. El-Chemaly has nothing to disclose. Conflict of interest: B.A. Raby reports grants from NIH, outside the submitted work. Conflict of interest: V. Gudnason has nothing to disclose. Conflict of interest: D.L. DeMeo reports grants from Novartis and Bayer, during the conduct of the study. Conflict of interest: E.K. Silverman reports grants from GlaxoSmithKline and Bayer, during the conduct of the study. Conflict of interest: H. Hatabu reports grants from Canon Medical Systems Inc. and Konica-Minolta Inc., and personal fees for consultancy from Mitsubishi Chemical Inc. and Canon Medical Systems Inc., outside the submitted work. Conflict of interest: I. DeVivo has nothing to disclose. Conflict of interest: M.H. Cho reports grants from GlaxoSmithKline and Bayer, and consultancy and/or speaker fees from Genentech, AstraZeneca and Illumina, outside the submitted work. Conflict of interest: G. Gudmundsson has nothing to disclose. Conflict of interest: G.M. Hunninghake reports personal fees from Gerson Lehrman Group and Boehringer Ingelheim, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Objectives: Pulmonary disease is a common extraarticular manifestation of RA associated with increased morbidity and mortality. No current strategies exist for screening this at-risk population for parenchymal lung disease, including emphysema and interstitial lung disease (ILD)., Methods: RA patients without a diagnosis of ILD or chronic obstructive pulmonary disease underwent prospective and comprehensive clinical, laboratory, functional and radiological evaluations. High resolution CT (HRCT) scans were scored for preclinical emphysema and preclinical ILD and evaluated for other abnormalities., Results: Pulmonary imaging and/or functional abnormalities were identified in 78 (74%) of 106 subjects; 45% had preclinical parenchymal lung disease. These individuals were older with lower diffusion capacity but had similar smoking histories compared with no disease. Preclinical emphysema (36%), the most commonly detected abnormality, was associated with older age, higher anti-cyclic citrullinated peptide antibody titres and diffusion abnormalities. A significant proportion of preclinical emphysema occurred among never smokers (47%) with a predominantly panlobular pattern. Preclinical ILD (15%) was not associated with clinical, laboratory or functional measures., Conclusion: We identified a high prevalence of undiagnosed preclinical parenchymal lung disease in RA driven primarily by isolated emphysema, suggesting that it may be a prevalent and previously unrecognized pulmonary manifestation of RA, even among never smokers. As clinical, laboratory and functional evaluations did not adequately identify preclinical parenchymal abnormalities, HRCT may be the most effective screening modality currently available for patients with RA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Rationale: Knowledge on biomarkers of interstitial lung disease is incomplete. Interstitial lung abnormalities (ILAs) are radiologic changes that may present in its early stages. Objectives: To uncover blood proteins associated with ILAs using large-scale proteomics methods. Methods: Data from two prospective cohort studies, the AGES-Reykjavik (Age, Gene/Environment Susceptibility-Reykjavik) study ( N  = 5,259) for biomarker discovery and the COPDGene (Genetic Epidemiology of COPD) study ( N  = 4,899) for replication, were used. Blood proteins were measured using DNA aptamers, targeting more than 4,700 protein analytes. The association of proteins with ILAs and ILA progression was assessed with regression modeling, as were associations with genetic risk factors. Adaptive Least Absolute Shrinkage and Selection Operator models were applied to bootstrap data samples to discover sets of proteins predictive of ILAs and their progression. Measurements and Main Results: Of 287 associations, SFTPB (surfactant protein B) (odds ratio [OR], 3.71 [95% confidence interval (CI), 3.20-4.30]; P  = 4.28 × 10 -67 ), SCGB3A1 (Secretoglobin family 3A member 1) (OR, 2.43 [95% CI, 2.13-2.77]; P  = 8.01 × 10 -40 ), and WFDC2 (WAP four-disulfide core domain protein 2) (OR, 2.42 [95% CI, 2.11-2.78]; P  = 4.01 × 10 -36 ) were most significantly associated with ILA in AGES-Reykjavik and were replicated in COPDGene. In AGES-Reykjavik, concentrations of SFTPB were associated with the rs35705950 MUC5B (mucin 5B) promoter polymorphism, and SFTPB and WFDC2 had the strongest associations with ILA progression. Multivariate models of ILAs in AGES-Reykjavik, ILAs in COPDGene, and ILA progression in AGES-Reykjavik had validated areas under the receiver operating characteristic curve of 0.880, 0.826, and 0.824, respectively. Conclusions: Novel, replicated associations of ILA, its progression, and genetic risk factors with numerous blood proteins are demonstrated as well as machine-learning-based models with favorable predictive potential. Several proteins are revealed as potential markers of early fibrotic lung disease.

Background: Interstitial lung abnormalities (ILA) are radiologic findings that may progress to idiopathic pulmonary fibrosis (IPF). Blood gene expression profiles can predict IPF mortality, but whether these same genes associate with ILA and ILA outcomes is unknown. This study evaluated if a previously described blood gene expression profile associated with IPF mortality is associated with ILA and all-cause mortality., Methods: In COPDGene and ECLIPSE study participants with visual scoring of ILA and gene expression data, we evaluated the association of a previously described IPF mortality score with ILA and mortality. We also trained a new ILA score, derived using genes from the IPF score, in a subset of COPDGene. We tested the association with ILA and mortality on the remainder of COPDGene and ECLIPSE., Results: In 1469 COPDGene (training n = 734; testing n = 735) and 571 ECLIPSE participants, the IPF score was not associated with ILA or mortality. However, an ILA score derived from IPF score genes was associated with ILA (meta-analysis of test datasets OR 1.4 [95% CI: 1.2-1.6]) and mortality (HR 1.25 [95% CI: 1.12-1.41]). Six of the 11 genes in the ILA score had discordant directions of effects compared to the IPF score. The ILA score partially mediated the effects of age on mortality (11.8% proportion mediated)., Conclusions: An ILA gene expression score, derived from IPF mortality-associated genes, identified genes with concordant and discordant effects on IPF mortality and ILA. These results suggest shared, and unique biologic processes, amongst those with ILA, IPF, aging, and death., (© 2022. The Author(s).)

Connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren syndrome (SS), and mixed connective tissue disease (MCTD). On histopathology of lung biopsy in CTD-related ILDs (CTD-ILDs), multi-compartment involvement is an important clue, and when present, should bring CTD to the top of the list of etiologic differential diagnoses. Diverse histologic patterns including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia, apical fibrosis, diffuse alveolar damage, and lymphoid interstitial pneumonia can be seen on histology in patients with CTD-ILDs. Although proportions of ILDs vary, the NSIP pattern accounts for a large proportion, especially in SSc, DM and/or PM and MCTD, followed by the UIP pattern. In RA patients, interstitial lung abnormality (ILA) is reported to occur in approximately 20-60% of individuals of which 35-45% will have progression of the CT abnormality. Subpleural distribution and greater baseline ILA involvement are risk factors associated with disease progression. Asymptomatic CTD-ILDs or ILA patients with normal lung function and without evidence of disease progression can be followed without treatment. Immunosuppressive or antifibrotic agents for symptomatic and/or fibrosing CTD-ILDs can be used in patients who require treatment., (© 2022 The Authors.)

Background: Most pulmonary conditions reduce FVC, but studies of patients with combined pulmonary fibrosis and emphysema demonstrate that reductions in FVC are less than expected when these two conditions coexist clinically., Research Question: Do interstitial lung abnormalities (ILAs), chest CT imaging findings that may suggest an early stage of pulmonary fibrosis in individuals with undiagnosed disease, affect the association between emphysema and FVC?, Study Design and Methods: Measures of ILA and emphysema were available for 9,579 and 5,277 participants from phases 1 (2007-2011) and 2 (2012-2016) of the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study (COPDGene), respectively. ILA were defined by Fleischner Society guidelines. Adjusted linear regression models were used to assess the associations and interactions among ILA, emphysema, measures of spirometry, and lung function., Results: ILA were present in 528 (6%) and 580 (11%) of participants in phases 1 and 2 of COPDGene, respectively. ILA modified the association between emphysema and FVC (P < .0001 for interaction) in both phases. In phase 1, in those without ILA, a 5% increase in emphysema was associated with a reduction in FVC (-110 mL; 95% CI, -121 to -100 mL; P < .0001); however, in those with ILA, it was not (-11 mL; 95% CI, -53 to 31; P = .59). In contrast, no interaction was found between ILA and emphysema on total lung capacity or on diffusing capacity of carbon monoxide., Interpretation: The presence of ILA attenuates the reduction in FVC associated with emphysema., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: To explore the feasibility of Vector-Field DXR (VF-DXR) using optical flow method (OFM)., Methods: Five healthy volunteers and five COPD patients were studied. DXR was performed in the standing position using a prototype X-ray system (Konica Minolta Inc., Tokyo, Japan). During the examination, participants took several tidal breaths and one forced breath. DXR image file was converted to the videos with different frames per second (fps): 15 fps, 7.5 fps, five fps, three fps, and 1.5 fps. Pixel-value gradient was calculated by the serial change of pixel value, which was subsequently converted mathematically to motion vector using OFM. Color-coding map and vector projection into horizontal and vertical components were also tested., Results: Dynamic motion of lung and thorax was clearly visualized using VF-DXR with an optimal frame rate of 5 fps. Color-coding map and vector projection into horizontal and vertical components were also presented. VF-DXR technique was also applied in COPD patients., Conclusion: The feasibility of VF-DXR was demonstrated with small number of healthy subjects and COPD patients., Advances in Knowledge: A new Vector-Field Dynamic X-ray (VF-DXR) technique is feasible for dynamic visualization of lung, diaphragms, thoracic cage, and cardiac contour.

Rationale: Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. Objectives: We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high-attenuation areas, and FVC in four independent cohorts. Methods: We included participants with measured monocyte counts and computed tomographic (CT) imaging enrolled in MESA (Multi-Ethnic Study of Atherosclerosis, n  = 484), AGES-Reykjavik (Age/Gene Environment Susceptibility Study, n  = 3,547), COPDGene (Genetic Epidemiology of COPD, n  = 2,719), and the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, n  = 646). Measurements and Main Results: After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.0-1.8), AGES-Reykjavik (OR, 1.2; 95% CI, 1.1-1.3), COPDGene (OR, 1.3; 95% CI, 1.2-1.4), and ECLIPSE (OR, 1.2; 95% CI, 1.0-1.4). A higher monocyte count was associated with ILA progression over 5 years in AGES-Reykjavik (OR, 1.2; 95% CI, 1.0-1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater high-attenuation areas in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. Conclusions: Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.

Background: We assessed the difference in lung motion during inspiration/expiration between chronic obstructive pulmonary disease (COPD) patients and healthy volunteers using vector-field dynamic x-ray (VF-DXR) with optical flow method (OFM)., Methods: We enrolled 36 COPD patients and 47 healthy volunteers, classified according to pulmonary function into: normal, COPD mild, and COPD severe. Contrast gradient was obtained from sequential dynamic x-ray (DXR) and converted to motion vector using OFM. VF-DXR images were created by projection of the vertical component of lung motion vectors onto DXR images. The maximum magnitude of lung motion vectors in tidal inspiration/expiration, forced inspiration/expiration were selected and defined as lung motion velocity (LMV). Correlations between LMV with demographics and pulmonary function and differences in LMV between COPD patients and healthy volunteers were investigated., Results: Negative correlations were confirmed between LMV and % forced expiratory volume in one second (%FEV 1 ) in the tidal inspiration in the right lung (Spearman's rank correlation coefficient, r s = -0.47, p < 0.001) and the left lung (r s = -0.32, p = 0.033). A positive correlation between LMV and %FEV 1 in the tidal expiration was observed only in the right lung (r s = 0.25, p = 0.024). LMVs among normal, COPD mild and COPD severe groups were different in the tidal respiration. COPD mild group showed a significantly larger magnitude of LMV compared with the normal group., Conclusions: In the tidal inspiration, the lung parenchyma moved faster in COPD patients compared with healthy volunteers. VF-DXR was feasible for the assessment of lung parenchyma using LMV., (© 2022. The Author(s) under exclusive licence to European Society of Radiology.)

Objectives: Axillary lymphadenopathy from coronavirus disease 2019 (COVID-19) vaccine is an emerging phenomenon during unprecedented mass vaccinations, which can be incidentally found on computed tomography (CT) scans. This study investigated the incidence, predisposing factors, and imaging characteristics of vaccine-related axillary lymphadenopathy in patients with thoracic malignancy who underwent CT scans before and after COVID-19 vaccinations., Methods: The study included patients with thoracic malignancies who received two doses of mRNA-based COVID-19 vaccinations and had prevaccine and postvaccine chest CT scans. Postvaccine chest CT scan results were reviewed for increase in size of lymph nodes in the axilla and subpectoral areas, comparing with the prevaccine scan results. The cases with lymphadenopathy were further reviewed independently by two radiologists referring to clinical information to find whether lymphadenopathy was attributed to the vaccinations., Results: Vaccine-related axillary lymphadenopathy was noted in 21 of 232 patients (9.0%). The median short-axis diameter of the largest node was 7 mm (range: 5-14 mm). The median number of increased nodes was 4 (range: 1-10). The median time to the postvaccine scan revealing lymphadenopathy was 1.7 weeks (range: -2.9 to 6.6) from the second dose. Vaccine-related lymphadenopathy was noted more often in women than in men (18 of 144, 12.5% versus 3 of 88, 3.4%, respectively; p = 0.019) and with mRNA-1273 vaccines than BNT162b2 vaccines (6 of 28, 21% versus 15 of 204, 7.4%, respectively; p = 0.026)., Conclusions: The incidence of lymphadenopathy was 9%, with a median onset time of 1.7 weeks after the second vaccine dose. Female sex and vaccine type (mRNA-1273 vaccine) were associated with higher frequency of lymphadenopathy, providing initial observations to inform further investigations in larger cohorts., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Study Design: A case-control study of risk alleles for degenerative disc disease (DDD) using magnetic resonance (MR) imaging for phenotyping., Objective: We aim to provide the first statistically adequately powered study of the relationship between the presence of common risk alleles and occurrence of DDD in Eastern US population., Summary of Background Data: Many genetic predisposing factors have been identified in elevating the risk of DDD, including common variants in VDR, COL1A1, AGC1, COL9A2/3 genes., Methods: We utilized the Mass General Brigham (MGB) Biobank in which subjects' Medical Record is linked with genotyped data from single-nucleotide polymorphism (SNP) arrays. Subjects with lumbosacral spine MR imaging studies were used to construct the Cases cohort; the Biobank's Controls cohort was used as the Control cohort. Odds ratios (OR) and False-discovery-rate (FDR) q values from multiple-hypotheses-testing corrections were used to assess the likelihood of DDD given occurrence of the listed DDD risk alleles., Results: Four-hundred-fourteen subjects (mean age = 64, range = 27 to 94) were Cases and 925 Controls (mean age = 46, range = 21-61). A systematic search has identified 25 SNPs in 18 genes in the SNP arrays. At univariate level, rs1544410 in VDR was significantly associated with DDD for male subjects (odds ratio [OR] = 0.594, P = 0.011). After adjustment for all significant variants and demographics, three predictor variables had a significant association with the outcome, age (OR = 1.130, q < 0.0001), rs143383 (OR = 1.951, q = 0.056), and rs3737821 (OR = 2.701, q = 0.069). A novel variant-to-variant correlation rs143383:rs763110 had a significant adjusted OR = 7.933, q = 0.070)., Conclusion: In this large-scale study of common variants' correlation with the presence of DDD in the Northeast United States, we have found a novel and significant variant-to-variant interaction to be associated with the risk of developing DDD, corroborating and necessitating the inclusion of gene-gene interactions in predictive risk model development for DDD.Level of Evidence: 4., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate the association between tumor volume growth rate after the nadir and survival in patients with EGFR -mutant advanced non-small-cell lung cancer (NSCLC) treated with erlotinib., Materials and Methods: Seventy-one patients with EGFR -mutant advanced NSCLC treated with erlotinib were studied for computed tomography tumor volume kinetics during therapy. The tumor growth rate after nadir was obtained using a previously published analytic module for longitudinal volume tracking to study its relationship with overall survival (OS)., Results: The median tumor volume for the cohort was 19,842 mm 3 at baseline and 4,083 mm 3 at nadir. The median time to nadir was 6.2 months. The tumor growth rate after nadir for log e V (the natural logarithm of tumor volume measured in mm 3 ) was 0.11/mo on average for the cohort (SE: 0.014), which was very similar to the previously validated reference value of 0.12/mo to define slow and fast tumor growth. The OS of 48 patients with slow tumor growth (≤ 0.12/mo) was significantly longer compared with 23 patients with fast tumor growth (> 0.12/mo; median OS: 37.8 v 25.0 months; P = .0012). In Cox models, tumor growth rate was also associated with survival (regression coefficient: 3.9903; P = .0024; faster rate leads to increased hazards), after adjusting for time to nadir (regression coefficient: -0.0863; P = .0008; longer time to nadir leads to decreased hazards) and smoking history., Conclusion: In patients with EGFR -mutant advanced NSCLC treated with erlotinib, slower tumor growth rates after nadir were associated with longer OS, providing a rationale for using tumor growth rates to guide precision therapy for lung cancer., Competing Interests: Mizuki NishinoConsulting or Advisory Role: Daiichi Sankyo, AstraZenecaResearch Funding: Merck, Canon Medical Systems, AstraZeneca, Daiichi Sankyo Natalie I. VokesConsulting or Advisory Role: Sanofi Pasi A. JänneConsulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, ACEA Biosciences, Ignyta, LOXO Oncology, Eli Lilly, Araxes Biosciences, SFJ Pharmaceuticals, Voroni, Daiichi Sankyo, Biocartis, Novartis, Sanofi Oncology, Takeda Oncology, Silicon Therapeutics, Syndax, Nuvalent, Bayer, Esai, Mirati TherapeuticsResearch Funding: AstraZeneca, Boehringer Ingelheim, PUMA, Eli Lilly, Takeda Oncology, Daiichi Sankyo, Astellas, Revolution MedicinesStock and Other Ownership Interests: (including patents) Gatekeeper Pharmaceuticals, LOXO Oncology, LabCorpPatents, Royalties, Other Intellectual Property: Co-inventor on Dana-Farber Cancer Institute–owned patent on EGFR mutations licensed to LabCorp (postmarketing royalties received from this invention) Hiroto HatabuConsulting or Advisory Role: Canon Medical Systems Inc, Mitsubishi Chemical CoResearch Funding: Canon Inc, Canon Medical Systems Inc, Konica-Minolta Inc Bruce E. JohnsonResearch Funding: Canon Medical Systems, Novartis, Sola Fund for Lung Cancer Research, Shuster Lung Cancer ResearchPatents, Royalties, Other Intellectual Property: Post-marketing royalties for EGFR Mutation testing, Dana-Farber Cancer InstituteNo other potential conflicts of interest were reported.

The clinical importance of interstitial lung abnormality (ILA) is increasingly recognized. In July 2020, the Fleischner Society published a position paper about ILA. The purposes of this article are to summarize the definition, existing evidence, clinical management, and unresolved issues for ILA from a radiologic standpoint and to provide a practical guide for radiologists. ILA is a common incidental finding at CT and is often progressive and associated with worsened clinical outcomes. The hazard ratios for mortality range from 1.3 to 2.7 in large cohorts. Risk factors for ILA include age, smoking status, other inhalational exposures, and genetic factors (eg, gene encoding mucin 5B variant). Radiologists should systematically record the presence, morphologic characteristics, distribution, and subcategories of ILA (ie, nonsubpleural, subpleural nonfibrotic, and subpleural fibrotic), as these are informative for predicting progression and mortality. Clinically significant interstitial lung disease should not be considered ILA. Individuals with ILA are triaged into higher- and lower-risk groups depending on their risk factors for progression, and systematic follow-up, including CT, should be considered for the higher-risk group. Artificial intelligence-based automated analysis for ILA may be helpful, but further validation and improvement are needed. Radiologists have a central role in clinical management and research on ILA., (© RSNA, 2021.)

Pulmonary functional imaging may be defined as the regional quantification of lung function by using primarily CT, MRI, and nuclear medicine techniques. The distribution of pulmonary physiologic parameters, including ventilation, perfusion, gas exchange, and biomechanics, can be noninvasively mapped and measured throughout the lungs. This information is not accessible by using conventional pulmonary function tests, which measure total lung function without viewing the regional distribution. The latter is important because of the heterogeneous distribution of virtually all lung disorders. Moreover, techniques such as hyperpolarized xenon 129 and helium 3 MRI can probe lung physiologic structure and microstructure at the level of the alveolar-air and alveolar-red blood cell interface, which is well beyond the spatial resolution of other clinical methods. The opportunities, challenges, and current stage of clinical deployment of pulmonary functional imaging are reviewed, including applications to chronic obstructive pulmonary disease, asthma, interstitial lung disease, pulmonary embolism, and pulmonary hypertension. Among the challenges to the deployment of pulmonary functional imaging in routine clinical practice are the need for further validation, establishment of normal values, standardization of imaging acquisition and analysis, and evidence of patient outcomes benefit. When these challenges are addressed, it is anticipated that pulmonary functional imaging will have an expanding role in the evaluation and management of patients with lung disease., (© RSNA, 2021 .)

Screening for pulmonary fibrosis may help to identify early stages of the disease. We assessed the psychological impact of screening undiagnosed first-degree relatives of patients with pulmonary fibrosis by administering two validated measures after participants received their results: the Decisional Regret Scale and the Feelings About genomiC Testing Results Questionnaire. More than 90% of relatives reported either no or mild decisional regret. Increased measures of decisional regret and negative feelings were present in those found to have a low diffusion capacity of carbon monoxide or interstitial lung abnormalities. Results of telomere length and genetic testing did not significantly impact regret., Competing Interests: Competing interests: HH reports grants and personal fees from Canon Medical Systems Inc, grants from Konica-Minolta Inc, and personal fees from Mitsubishi Chemical Co outside the submitted work. IOR reports grants from Roche/Genentech during the conduct of the study, grants and personal fees from Genentech and personal fees from Boehringer and Bristol Myers Squibb outside the submitted work. GMH reports personal fees from Boehringer-Ingelheim, Gerson Lehrman Group and Mitsubishi Chemical outside the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Over the past few decades, pulmonary imaging technologies have advanced from chest radiography and nuclear medicine methods to high-spatial-resolution or low-dose chest CT and MRI. It is currently possible to identify and measure pulmonary pathologic changes before these are obvious even to patients or depicted on conventional morphologic images. Here, key technological advances are described, including multiparametric CT image processing methods, inhaled hyperpolarized and fluorinated gas MRI, and four-dimensional free-breathing CT and MRI methods to measure regional ventilation, perfusion, gas exchange, and biomechanics. The basic anatomic and physiologic underpinnings of these pulmonary functional imaging techniques are explained. In addition, advances in image analysis and computational and artificial intelligence (machine learning) methods pertinent to functional lung imaging are discussed. The clinical applications of pulmonary functional imaging, including both the opportunities and challenges for clinical translation and deployment, will be discussed in part 2 of this review. Given the technical advances in these sophisticated imaging methods and the wealth of information they can provide, it is anticipated that pulmonary functional imaging will be increasingly used in the care of patients with lung disease. © RSNA, 2021 Online supplemental material is available for this article.

Following the introduction of a novel pathological concept of usual interstitial pneumonia (UIP) by Liebow and Carrington in 1969, diffuse interstitial pneumonia has evolved into UIP, nonspecific interstitial pneumonia (NSIP), and interstitial lung abnormality (ILA); the histopathological and CT findings of these conditions reflect the required multidisciplinary team approach, involving pulmonologists, radiologists, and pathologists, for their diagnosis and management. Concomitantly, traction bronchiectasis and bronchiolectasis have been recognized as the most persistent and important indices of the severity and prognosis of fibrotic lung diseases. The traction bronchiectasis index (TBI) can stratify the prognoses of patients with ILAs. In this review, the evolutionary concepts of UIP, NSIP, and ILAs are summarized in tables and figures, with a demonstration of the correlation between CT findings and pathologic evaluation. The CT-based UIP score is being proposed to facilitate a better understanding of the spectrum of pulmonary fibrosis, from ILAs to UIP, with emphasis on traction bronchiectasis/bronchiolectasis., Competing Interests: Dr. Hatabu reports grants from Canon Medical Systems Inc, grants from Konica Minolta Inc, personal fees from Mitsubishi Chemical Co, personal fees from Canon Medical Systems Inc, outside the submitted work. Other authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Rationale: The association between aging and idiopathic pulmonary fibrosis has been established. The associations between aging-related biomarkers and interstitial lung abnormalities (ILA) have not been comprehensively evaluated. Objectives: To evaluate the associations among aging biomarkers, ILA, and all-cause mortality. Methods: In the FHS (Framingham Heart Study), we evaluated associations among plasma biomarkers (IL-6, CRP [C-reactive protein], TNFR [tumor necrosis factor α receptor II], GDF15 [growth differentiation factor 15], cystatin-C, HGBA1C [Hb A1C], insulin, IGF1 [insulin-like growth factor 1], and IGFBP1 [IGF binding protein 1] and IGFBP3]), ILA, and mortality. Causal inference analysis was used to determine whether biomarkers mediated age. GDF15 results were replicated in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) Study. Measurements and Main Results: In the FHS, there were higher odds of ILA per increase in natural log-transformed GDF15 (odds ratio [95% confidence interval], 3.4 [1.8-6.4]; P  = 0.0002), TNFR (3.1 [1.6-5.8]; P  = 0.004), IL-6 (1.8 [1.4-2.4]; P  < 0.0001), and CRP (1.7 [1.3-2.0]; P  < 0.0001). In the FHS, after adjustment for multiple comparisons, no biomarker was associated with increased mortality, but the associations of GDF15 (hazard ratio, 2.0 [1.1-3.5]; P  = 0.02), TNFR (1.8 [1.0-3.3]; P  = 0.05), and IGFBP1 (1.3 [1.1-1.7]; P  = 0.01) approached significance. In the COPDGene Study, higher natural log-transformed GDF15 was associated with ILA (odds ratio, 8.1 [3.1-21.4]; P  < 0.0001) and mortality (hazard ratio, 1.6 [1.1-2.2]; P  = 0.01). Causal inference analysis showed that the association of age with ILA was mediated by IL-6 ( P  < 0.0001) and TNFR ( P  = 0.002) and was likely mediated by GDF15 ( P  = 0.008) in the FHS and was mediated by GDF15 ( P  = 0.001) in the COPDGene Study. Conclusions: Some aging-related biomarkers are associated with ILA. GDF15, in particular, may explain some of the associations among age, ILA, and mortality.

Objective: To determine the association between novel lifestyle factors on risk of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD), define the threshold at which smoking increases RA-ILD risk, and calculate the degree to which known lifestyle and clinical factors predict RA-ILD., Methods: This nested case-control study matched incident RA-ILD cases to RA non-ILD controls on age, sex, RA duration, rheumatoid factor, and time from exposure assessment to RA-ILD. Exposures included education, BMI, smoking, anticyclic citrullinated peptide antibodies, race, joint erosions, rheumatoid nodules, C-reactive protein (CRP), disease activity score, functional status, disease-modifying antirheumatic drug use, and glucocorticoid use. OR for each exposure on risk of RA-ILD were obtained from logistic regression models. Area under the curve (AUC) was calculated based on all lifestyle and clinical exposures., Results: We identified 84 incident RA-ILD cases and 233 matched controls. After adjustment, obesity, high-positive CRP (≥ 10 mg/L), and poor functional status (multidimensional Health Assessment Questionnaire [MDHAQ] ≥ 1) were associated with increased risk of RA-ILD (OR 2.42, 95% CI 1.11-5.24 vs normal BMI; OR 2.61, 95% CI 1.21-5.64 vs CRP < 3 mg/L; OR 3.10, 95% CI 1.32-7.26 vs MDHAQ < 0.2). Smoking 30 pack-years or more was strongly associated with risk of RA-ILD compared to never smokers (OR 6.06, 95% CI 2.72-13.5). Together, lifestyle and clinical risk factors for RA-ILD had an AUC of 0.79 (95% CI 0.73-0.85)., Conclusion: Obesity, CRP, functional status, and extensive smoking may be novel risk factors for RA-ILD that may be useful for RA-ILD risk assessment and prevention. The overall ability to predict RA-ILD remains modest., (Copyright © 2021 by the Journal of Rheumatology.)

Dynamic X-ray (DXR) is a functional imaging technique that uses sequential images obtained by a flat-panel detector (FPD). This article aims to describe the mechanism of DXR and the analysis methods used as well as review the clinical evidence for its use. DXR analyzes dynamic changes on the basis of X-ray translucency and can be used for analysis of diaphragmatic kinetics, ventilation, and lung perfusion. It offers many advantages such as a high temporal resolution and flexibility in body positioning. Many clinical studies have reported the feasibility of DXR and its characteristic findings in pulmonary diseases. DXR may serve as an alternative to pulmonary function tests in patients requiring contact inhibition, including patients with suspected or confirmed coronavirus disease 2019 or other infectious diseases. Thus, DXR has a great potential to play an important role in the clinical setting. Further investigations are needed to utilize DXR more effectively and to establish it as a valuable diagnostic tool., Competing Interests: Reserch funding from Canon Inc., Canon Medical Systems Inc., and Konica-Minolta Inc.; Consultant to Canon Medical Systems Inc., and Mitsubishi Chemical Co. for outside of the submitted work. Other authors have no conflict of interest., (Copyright © 2021 The Korean Society of Radiology.)

The objectives of the study were to characterize the tumor burden dynamics on serial computed tomography scans in patients with advanced non-small-cell lung cancer treated with first-line pembrolizumab and to identify imaging markers for prolonged overall survival (OS)., Materials and Methods: Eighty-eight patients treated with first-line pembrolizumab monotherapy were evaluated on serial computed tomography scans to characterize their quantitative tumor burden during therapy. Tumor burden dynamics were studied for the association with OS., Results: The overall response rate was 42% (37/88), with the median tumor burden changes at the best overall response of -18.3% (range, -100.0% to +103.6%). Response rates were higher in men than in women ( P = .05) and in patients with higher programmed cell death ligand-1 expression levels ( P = .02). Tumor burden stayed below the baseline burden throughout therapy in 55 patients (63%). In an 8-week landmark analysis, patients with tumor burden below the baseline burden during the first 8 weeks of therapy had longer OS compared with patients who had ≥ 0% increase (median OS, 30.7 v 16.2 months; hazard ratio [HR] = 0.44; P = .01). In the extended Cox models, patients whose tumor burden stayed below the baseline burden throughout therapy had significantly reduced hazards of death (HR = 0.41, P = .003, univariate; HR = 0.35, P = .02, multivariate). Only one patient (1.1%) experienced pseudoprogression with initial tumor increase and subsequent tumor regression., Conclusion: In patients with advanced non-small-cell lung cancer treated with first-line single-agent pembrolizumab, tumor burden reduction below the baseline burden during therapy was an independent marker for prolonged OS, which may serve as a practical guide for treatment decisions., (© 2021 by American Society of Clinical Oncology.)

This review article aims to address mysteries existing between Interstitial Lung Abnormality (ILA) and Nonspecific Interstitial Pneumonia (NSIP). The concept and definition of ILA are based upon CT scans from multiple large-scale cohort studies, whereas the concept and definition of NSIP originally derived from pathology with evolution to multi-disciplinary diagnosis. NSIP is the diagnosis as Interstitial Lung Disease (ILD) with clinical significance, whereas only a part of subjects with ILA have clinically significant ILD. Eventually, both ILA and NSIP must be understood in the context of chronic fibrosing ILD and progressive ILD, which remains to be further investigated., Competing Interests: Dr. Hatabu reports grants from Canon Medical Systems Inc, grants from Konica Minolta Inc, personal fees from Mitsubishi Chemical Co, personal fees from Canon Medical Systems Inc, outside the submitted work. Other authors have no conflicts of interest to disclose., (© 2021 The Authors. Published by Elsevier Ltd.)

Purpose: The aim of this study is to assess the role of traction bronchiectasis/bronchiolectasis and its progression as a predictor for early fibrosis in interstitial lung abnormalities (ILA)., Methods: Three hundred twenty-seven ILA participants out of 5764 in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who had undergone chest CT twice with an interval of approximately five-years were enrolled in this study. Traction bronchiectasis/bronchiolectasis index (TBI) was classified on a four-point scale: 0, ILA without traction bronchiectasis/bronchiolectasis; 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; 2, ILA with mild to moderate traction bronchiectasis; 3, ILA and severe traction bronchiectasis and/or honeycombing. Traction bronchiectasis (TB) progression was classified on a five-point scale: 1, Improved; 2, Probably improved; 3, No change; 4, Probably progressed; 5, Progressed. Overall survival (OS) among participants with different TB Progression Score and between the TB progression group and No TB progression group was also investigated. Hazard radio (HR) was estimated with Cox proportional hazards model., Results: The higher the TBI at baseline, the higher TB Progression Score (P < 0.001). All five participants with TBI = 3 at baseline progressed; 46 (90 %) of 51 participants with TBI = 2 progressed. TB progression was also associated with shorter OS with statistically significant difference (adjusted HR = 1.68, P < 0.001)., Conclusion: TB progression was visualized on chest CT frequently and clearly. It has the potential to be the predictor for poorer prognosis of ILA., (© 2021 The Author(s).)

Purpose: To describe the imaging findings of lung infiltration by leukemia and differential findings of lymphoid and myeloid leukemias., Materials and Methods: Through a search of electronic medical records from 2005 to 2017, we identified 21 patients with pathologically proven lung involvement by leukemia. Concurrent CT findings were analyzed by 2 chest radiologists in consensus for ground glass or consolidative opacities, septal thickening, bronchovascular bundle thickening, pulmonary nodules, pulmonary masses, and hilar and mediastinal lymphadenopathy., Results: There were 13 cases of lymphoid leukemias and 8 of myeloid leukemias. Nodules and masses were the most common imaging feature (n = 13, 62%). Bronchovascular bundle thickening and hilar lymphadenopathy were exclusively seen in lymphoid leukemias (P = 0.01 and P = 0.006). Centrilobular nodules were also exclusively seen in 3 patients with chronic lymphocytic leukemia., Conclusion: Lung infiltration by leukemia presents most commonly with nodules or masses, but interstitial abnormalities such as bronchovascular bundle thickening were seen as well. Radiologists should consider leukemic infiltration in the differential diagnosis for nodules, including centrilobular nodules, in these patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Interstitial lung abnormalities (ILA) can be detected on computed tomography (CT) in lung cancer patients and have an association with mortality in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study is to demonstrate the significance of ILA for mortality in patients with stage I NSCLC using Boston Lung Cancer Study cohort., Methods: Two hundred and thirty-one patients with stage I NSCLC from 2000 to 2011 were investigated in this retrospective study (median age, 69 years; 93 males, 138 females). ILA was scored on baseline CT scans prior to treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA) by a sequential reading method. ILA score 2 was considered the presence of ILA. The difference of overall survival (OS) for patients with different ILA scores were tested via log-rank test and multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) including ILA score, age, sex, smoking status, and treatment as the confounding variables., Results: ILA was present in 22 out of 231 patients (9.5%) with stage I NSCLC. The presence of ILA was associated with shorter OS (patients with ILA score 2, median 3.85 years [95% confidence interval (CI): 3.36 - not reached (NR)]; patients with ILA score 0 or 1, median 10.16 years [95%CI: 8.65 - NR]; P <  0.0001). In a Cox proportional hazards model, the presence of ILA remained significant for increased risk for death (HR = 2.88, P = 0.005) after adjusting for age, sex, smoking and treatment., Conclusions: ILA was detected on CT in 9.5% of patients with stage I NSCLC. The presence of ILA was significantly associated with a shorter OS and could be an imaging marker of shorter survival in stage I NSCLC.

An increased incidence of lung cancer is well known among patients with idiopathic pulmonary fibrosis. It is not known whether interstitial lung abnormalities, i.e. early fibrotic changes of the lung, are a risk factor for lung cancer in the general population.The study's objective was to assess whether interstitial lung abnormalities were associated with diagnoses of, and mortality from, lung cancer and other cancers. Data from the AGES-Reykjavik study, a cohort of 5764 older Icelandic adults, were used. Outcome data were ascertained from electronic medical records. Gray's tests, Cox proportional hazards models and proportional subdistribution hazards models were used to analyse associations of interstitial lung abnormalities with lung cancer diagnoses and lung cancer mortality as well as diagnoses and mortality from all cancers.There was a greater cumulative incidence of lung cancer diagnoses (p<0.001) and lung cancer mortality (p<0.001) in participants with interstitial lung abnormalities than in others. Interstitial lung abnormalities were associated with an increased hazard of lung cancer diagnosis (hazard ratio 2.77) and lung cancer mortality (hazard ratio 2.89) in adjusted Cox models. Associations of interstitial lung abnormalities with all cancers were found in models including lung cancers but not in models excluding lung cancers.People with interstitial lung abnormalities are at increased risk of lung cancer and lung cancer mortality, but not of other cancers. This implies that an association between fibrotic and neoplastic diseases of the lung exists from the early stages of lung fibrosis and suggests that interstitial lung abnormalities could be considered as a risk factor in lung cancer screening efforts., Competing Interests: Conflict of interest: G.T. Axelsson has nothing to disclose. Conflict of interest: R.K. Putman reports grants from NIH, during the conduct of the study. Conflict of interest: T. Aspelund has nothing to disclose. Conflict of interest: E.F. Gudmundsson has nothing to disclose. Conflict of interest: T. Hida has nothing to disclose. Conflict of interest: T. Araki has nothing to disclose. Conflict of interest: M. Nishino reports personal fees for consultancy from Daiichi Sankyo and AstraZeneca; honoraria from Roche; and grants from Merck, AstraZeneca, Canon Medical Systems and NIH (R01CA203636, U01CA209414, R01HL111024), outside the submitted work. Conflict of interest: H. Hatabu reports grants from Canon Medical System Inc. and Konica-Minolta Inc., personal fees for consultancy from Mitsubishi Chemical Inc. and personal fees for advisory board work from Canon Medical System Inc., outside the submitted work. Conflict of interest: V. Gudnason has nothing to disclose. Conflict of interest: G.M. Hunninghake reports personal fees from Genentech, Boehringer Ingelheim, The Gerson Lehrman Group and Mitsubishi Chemical, outside the submitted work. Conflict of interest: G. Gudmundsson has nothing to disclose., (Copyright ©ERS 2020.)

The connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren's syndrome (SS), and mixed connective tissue disease (MCTD). In RA patients in particular, interstitial lung abnormality (ILA) (of varying degrees; severe vs. mild) is reported to occur in approximately 20-60 % of individuals and CT disease progression occurs in approximately 35-45 % of them. The ILAs have been associated with a spectrum of functional and physiologic decrement. The identification of progressive ILA may enable appropriate surveillance and the commencement of treatment with the goal of improving morbidity and mortality rates of established RA-ILD. Subpleural distribution and higher baseline ILA/ILD extent were risk factors associated with disease progression. At histopathologic analysis, connective tissue disease-related interstitial lung diseases (CTD-ILDs) are diverse and include nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), apical fibrosis, diffuse alveolar damage (DAD), and lymphoid interstitial pneumonia (LIP). Even though proportions of ILDs vary, NSIP pattern accounts for a large proportion, especially in PSS, DM/PM and MCTD, followed by UIP pattern. Evidence has been published that treatment of subclinical CT lung abnormalities showing a tendency to progress to ILD may stabilize the CT alterations. The identification of subclinical lung abnormalities can be appropriate in the management of the disease and CT appears to be the gold standard for the evaluation of lung parenchyma., Competing Interests: The authors report no declarations of interest., (© 2020 The Authors.)

Background: A multidisciplinary team approach to the management of esophageal cancer patients leads to better clinical decisions., Purpose: The contribution of CT, endoscopic and laparoscopic ultrasound to clinical staging and treatment selection by multidisciplinary tumor boards (MTB) in patients with esophageal cancer is well documented. However, there is a paucity of data addressing the role that FDG-PET/CT (PET/CT) plays to inform the clinical decision-making process at MTB conferences. The aim of this study was to assess the impact and contribution of PET/CT to clinical management decisions and to the plan of care for esophageal cancer patients at the MTB conferences held at our institution., Materials and Methods: This IRB approved study included all the cases discussed in the esophageal MTB meetings over a year period. The information contributed by PET/CT to MTB decision making was grouped into four categories. Category I , no additional information provided for clinical management; category II , equivocal and misguiding information; category III , complementary information to other imaging modalities, and category IV , information that directly changed clinical management. The overall impact on management was assessed retrospectively from prospectively discussed clinical histories, imaging, histopathology, and the official minutes of the MTB conferences., Results: 79 patients (61 males and 18 females; median age, 61 years, range, 33-86) with esophageal cancer (53 adenocarcinomas and 26 squamous cell carcinomas) were included. The contribution of PET/CT-derived information was as follows: category I in 50 patients (63%); category II in 3 patients (4%); category III in 8 patients (10%), and category IV information in 18 patients (23%). Forty-five patients (57%) had systemic disease, and in 5 (11%) of these, metastatic disease was only detected by PET/CT. In addition, PET/CT detected previously unknown recurrence in 4 (9%) of 43 patients. In summary, PET/CT provided clinically useful information to guide management in 26 of 79 esophageal cancer patients (33%) discussed at the MTB., Conclusion: The study showed that PET/CT provided additional information and changed clinical management in 1 out of 3 (33%) esophageal cancer cases discussed at MTB conferences. These results support the inclusion whenever available, of FDG-PET/CT imaging information to augment and improve the patient management decision process in MTB conferences., Competing Interests: The uploaded manuscript entitled “Contribution of FDG-PET/CT to the Management of Esophageal Cancer Patients at Multidisciplinary Tumor Board Conferences” has been read and approved by all authors, who attest not to have any conflict of interests or financial disclosures to make., (© 2020 The Author(s).)

Purpose: Investigate the incidence and imaging characteristics of radiologically-evident immune-related adverse events (irAEs) on body CT in patients with small-cell lung cancer (SCLC) treated with immune-checkpoint inhibitors., Methods: The study included 53 patients with relapsed/refractory SCLC (27 men, 26 women) treated with PD-1/PD-L1 inhibitors alone or in combination with CTLA-4 inhibition, who had baseline and at least one follow-up body CT during therapy. Body CT scans were reviewed to detect and characterize organ-specific irAEs including thyroiditis, pneumonitis, hepatitis, pancreatitis, enteritis, and colitis., Results: Nineteen patients (36 %) developed radiologically-evident irAEs. The median time from therapy initiation to irAE onset was 7.1 weeks. Pneumonitis and colitis were most common, noted in 9 patients (17 %) each. Seven colitis cases demonstrated pancolitis, and two cases showed segmental colitis associated with diverticulosis. The common radiographic patterns of pneumonitis were acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) pattern (n = 4) and cryptogenic organizing pneumonia (COP) pattern (n = 3). Other irAEs included thyroiditis (n = 3), enteritis (n = 2), hepatitis (n = 1), and pancreatitis (n = 1). Older age (p = 0.03) and prior radiotherapy to any organ (p = 0.03) was associated with overall irAEs. Prior chest radiotherapy was significantly associated with pneumonitis or thyroiditis (p = 0.0004)., Conclusion: Radiologically-evident irAEs were noted on body CT in 36 % of patients with SCLC treated with immune-checkpoint inhibitors. Colitis and pneumonitis were most common. Prior chest radiotherapy was a predictor of the development of both pneumonitis and thyroiditis. Awareness of risk factors and CT findings of irAEs is important for early detection and accurate diagnosis of potentially serious immunotherapy toxicities., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pulmonary MRI provides structural and quantitative functional images of the lungs without ionizing radiation, but it has had limited clinical use due to low signal intensity from the lung parenchyma. The lack of radiation makes pulmonary MRI an ideal modality for pediatric examinations, pregnant women, and patients requiring serial and longitudinal follow-up. Fortunately, recent MRI techniques, including ultrashort echo time and zero echo time, are expanding clinical opportunities for pulmonary MRI. With the use of multicoil parallel acquisitions and acceleration methods, these techniques make pulmonary MRI practical for evaluating lung parenchymal and pulmonary vascular diseases. The purpose of this Fleischner Society position paper is to familiarize radiologists and other interested clinicians with these advances in pulmonary MRI and to stratify the Society recommendations for the clinical use of pulmonary MRI into three categories: (a) suggested for current clinical use, (b) promising but requiring further validation or regulatory approval, and (c) appropriate for research investigations. This position paper also provides recommendations for vendors and infrastructure, identifies methods for hypothesis-driven research, and suggests opportunities for prospective, randomized multicenter trials to investigate and validate lung MRI methods., (© RSNA, 2020.)

Pulmonary MRI can now provide high-resolution images that are sensitive to early disease and specific to inflammation in cystic fibrosis (CF) lung disease. With specificity and function limited via computed tomography (CT), there are significant advantages to MRI. Many of the modern MRI techniques can be performed throughout life, and can be employed to understand changes over time, in addition to quantification of treatment response. Proton density and T 1 /T 2 contrast images can be obtained within a single breath-hold, providing depiction of structural abnormalities and active inflammation. Modern radial and/or spiral ultrashort echo-time (UTE) techniques rival CT in resolution for depiction and quantification of structure, for both airway and parenchymal abnormalities. Contrast perfusion MRI techniques are now utilized routinely to visualize changes in pulmonary and bronchial circulation that routinely occur in CF lung disease, and noncontrast techniques are moving closer to clinical translation. Functional information can be obtained from noncontrast proton images alone, using techniques such as Fourier decomposition. Hyperpolarized-gas MRI, increasingly using 129 Xe, is now becoming more widespread and has been demonstrated to have high sensitivity to early airway obstruction in CF via ventilation MRI. The sensitivity of 129 Xe MRI promises future use in personalized medicine, management of early CF lung disease, and in future clinical trials. By combining structural and functional techniques, with or without hyperpolarized gases, regional structure-function relationships can be obtained, giving insight into the pathophysiology of disease and improved clinical management. This article reviews the modern MRI techniques that can routinely be employed for CF lung disease in nearly any large medical center. Level of Evidence: 4 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: To determine the accuracy of quantitative CT to diagnose pulmonary edema compared to qualitative CT and CXR and to determine a threshold Hounsfield unit (HU) measurement for pulmonary edema on CT examinations., Method: Electronic medical records were searched for patients with a billing diagnosis of heart failure and a Chest CT and CXR performed within three hours between 1/1/2016 to 10/1/2016, yielding 100 patients. CXR and CT examinations were scored for the presence and severity of edema, using a 0-5 scale, and CT HU measurements were obtained in each lobe. Polyserial correlation coefficients evaluated the association between CT HUs and CXR scores, and receiver operating characteristic (ROC) curve analysis determined a cutoff CT HU value for identification of pulmonary edema., Results: Correlation between CT HU and CXR score was moderately strong (r = 0.585-0.685) with CT HU measurements demonstrating good to excellent accuracy in differentiating between no edema (grade 0) and mild to severe edema (grades 1-5) in every lobe, with AUCs ranging between 0.869 and 0.995. The left upper lobe demonstrated the highest accuracy, using a cutoff value of -825 HU (AUC of 0.995, sensitivity = 100 % and specificity = 95.1 %). Additionally, qualitative CT evaluation was less sensitive (84 %) than portable CXR in identifying pulmonary edema. However, quantitative CT evaluation was as sensitive as portable CXR (100 %) and highly specific (95 %)., Conclusions: Quantitative CT enables the identification of pulmonary edema with high accuracy and demonstrates a greater sensitivity than qualitative CT in assessment of pulmonary edema., (© 2020 Published by Elsevier Ltd.)

BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used in cancer treatment, and a subset of patients undergo pseudoprogression. Recognizing the incidence of pseudoprogression is critical for clinical practice.PurposeTo evaluate by systematic review and meta-analysis the incidence of pseudoprogression in cancer treatment with ICIs, and compare the incidence according to response criteria, tumor types, and immunotherapeutic agents.Materials and MethodsMedline and Embase were searched to identify relevant studies published before December 31, 2018. Clinical trials, post hoc analysis of clinical trials, and prospective studies on ICI treatment in patients with malignant solid tumors were included. Pooled incidence of pseudoprogression for all included studies, per definition of pseudoprogression, cancer type, and drug type, was obtained by random-effects models with inverse variance weighting model.ResultsSeventeen studies with 3402 patients were analyzed. The pooled incidence of pseudoprogression was 6.0% (95% confidence interval: 5.0%, 7.0%). The definition of pseudoprogression were divided into four categories: progressive disease followed by partial response (PR) or complete response (CR) but not stable disease (SD) with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (six studies); progressive disease followed by SD or PR or CR with RECIST 1.1 (five studies); progressive disease followed by SD or PR or CR with RECIST 1.0 (three studies); and progressive disease followed by SD or PR or CR with immune-related response criteria (irRC) (three studies). Incidence of pseudoprogression varied from 4.5% to 8.0% per definition, ranged from 5.0% to 7.0% per cancer type, and was 5.6% with the monotherapy of programmed cell death-1 inhibitor.ConclusionThe overall incidence of pseudoprogression was 6.0% and was less than 10% in subgroup analyses according to the definitions of pseudoprogression, cancer type, and immune checkpoint inhibitor type. Varying definitions across trials and studies indicates the need for uniform criteria of pseudoprogression for solid tumors.© RSNA, 2020 Online supplemental material is available for this article. See also the article by Dodd and MacDermott in this issue.