Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial.

BACKGROUND: Previous phase 2 trials of neoadjuvant anti-PD-1 or anti-PD-L1 monotherapy in patients with early-stage non-small-cell lung cancer have reported major pathological response rates in the range of 15-45%. Evidence suggests that stereotactic body radiotherapy might be a potent immunomodulator in advanced non-small-cell lung cancer (NSCLC). In this trial, we aimed to evaluate the use of stereotactic body radiotherapy in patients with early-stage NSCLC as an immunomodulator to enhance the anti-tumour immune response associated with the anti-PD-L1 antibody durvalumab. METHODS: We did a single-centre, open-label, randomised, controlled, phase 2 trial, comparing neoadjuvant durvalumab alone with neoadjuvant durvalumab plus stereotactic radiotherapy in patients with early-stage NSCLC, at NewYork-Presbyterian and Weill Cornell Medical Center (New York, NY, USA). We enrolled patients with potentially resectable early-stage NSCLC (clinical stages I-IIIA as per the 7th edition of the American Joint Committee on Cancer) who were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients were randomly assigned (1:1) to either neoadjuvant durvalumab monotherapy or neoadjuvant durvalumab plus stereotactic body radiotherapy (8 Gy × 3 fractions), using permuted blocks with varied sizes and no stratification for clinical or molecular variables. Patients, treating physicians, and all study personnel were unmasked to treatment assignment after all patients were randomly assigned. All patients received two cycles of durvalumab 3 weeks apart at a dose of 1·12 g by intravenous infusion over 60 min. Those in the durvalumab plus radiotherapy group also received three consecutive daily fractions of 8 Gy stereotactic body radiotherapy delivered to the primary tumour immediately before the first cycle of durvalumab. Patients without systemic disease progression proceeded to surgical resection. The primary endpoint was major pathological response in the primary tumour. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrial.gov, NCT02904954, and is ongoing but closed to accrual. FINDINGS: Between Jan 25, 2017, and Sept 15, 2020, 96 patients were screened and 60 were enrolled and randomly assigned to either the durvalumab monotherapy group (n=30) or the durvalumab plus radiotherapy group (n=30). 26 (87%) of 30 patients in each group had their tumours surgically resected. Major pathological response was observed in two (6·7% [95% CI 0·8-22·1]) of 30 patients in the durvalumab monotherapy group and 16 (53·3% [34·3-71·7]) of 30 patients in the durvalumab plus radiotherapy group. The difference in the major pathological response rates between both groups was significant (crude odds ratio 16·0 [95% CI 3·2-79·6]; p<0·0001). In the 16 patients in the dual therapy group with a major pathological response, eight (50%) had a complete pathological response. The second cycle of durvalumab was withheld in three (10%) of 30 patients in the dual therapy group due to immune-related adverse events (grade 3 hepatitis, grade 2 pancreatitis, and grade 3 fatigue and thrombocytopaenia). Grade 3-4 adverse events occurred in five (17%) of 30 patients in the durvalumab monotherapy group and six (20%) of 30 patients in the durvalumab plus radiotherapy group. The most frequent grade 3-4 events were hyponatraemia (three [10%] patients in the durvalumab monotherapy group) and hyperlipasaemia (three [10%] patients in the durvalumab plus radiotherapy group). Two patients in each group had serious adverse events (pulmonary embolism [n=1] and stroke [n=1] in the durvalumab monotherapy group, and pancreatitis [n=1] and fatigue [n=1] in the durvalumab plus radiotherapy group). No treatment-related deaths or deaths within 30 days of surgery were reported. INTERPRETATION: Neoadjuvant durvalumab combined with stereotactic body radiotherapy is well tolerated, safe, and associated with a high major pathological response rate. This neoadjuvant strategy should be validated in a larger trial. FUNDING: AstraZeneca.

Central paradiaphragmatic middle lobe involvement in nonspecific interstitial pneumonia.

OBJECTIVES: Nonspecific interstitial pneumonia (NSIP) lacks specific diagnostic guidelines or criteria for imaging diagnosis, and the need for more reliable computed tomography (CT) characterization remains. We hypothesized that central paradiaphragmatic middle lobe (ML) involvement is present in most patients with NSIP. The purpose of this study was to evaluate the prevalence of ML involvement and thus to assess its potential as a unique feature of NSIP. METHODS: We conducted a retrospective CT-imaging review of 40 patients with biopsy-proven (7/40, 18%) or clinically established (33/40, 82%) NSIP. Three subspecialty-trained thoracic radiologists reviewed CTs for ML involvement both independently and in consensus, and additional CT findings previously described in NSIP independently. RESULTS: ML involvement was present in most cases (70%, 28/40, independent review, 78%, 31/40, consensus reading), with substantial agreement among all three readers (κ = 0.65). Fibrosis was present in almost all cases (93%, 37/40). Subpleural sparing occurred in one-third of patients (30%, 12/40). Homogeneity (48%, 19/40), central bronchiectasis (45%, 18/40), and peripheral bronchiectasis (53%, 21/40) were present in about half of patients. Apart from substantial inter-reader agreement on fibrosis (κ = 0.65), the above-mentioned imaging characteristics had fair to slight universal agreement (κ = 0.07-0.30). CONCLUSIONS: Central paradiaphragmatic ML ground glass attenuation superimposed on reticulation and traction bronchiectasis occurs in most patients with NSIP, with high interobserver agreement. KEY POINTS: • Central paradiaphragmatic middle lobe ground glass attenuation superimposed on reticulation and traction bronchiectasis is common in nonspecific interstitial pneumonia (NSIP). • This finding occurs more frequently than subpleural sparing and has a better interobserver agreement.

Thoracic Manifestations of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is one of the most common chronic systemic inflammatory diseases and the most common chronic inflammatory arthritis. Classically a progressive symmetric polyarthritis, RA is characterized by inflammation, erosions, bone loss, and joint destruction. Up to half of patients with RA exhibit extra-articular manifestations (EAMs), which may precede articular disease and are more common in patients with seropositive RA (patients with detectable serum levels of rheumatoid factor and/or anticitrullinated peptide antibodies). Cardiovascular and pulmonary EAMs are the largest contributors to morbidity and mortality in RA and may be especially devastating. Imaging has a significant role in diagnosing these EAMs and assessing response to treatment. Although treatment with disease-modifying antirheumatic drugs has redefined the natural history of RA and helped many patients achieve low disease activity, patients are at risk for treatment-related complications, as well as infections. The clinical features of drug-induced lung disease and infection can overlap considerably with those of EAMs, presenting a diagnostic challenge. Radiologists, by recognizing the imaging characteristics and evolution of these various processes, are essential in diagnosing and distinguishing among EAMs, treatment-related complications, and unrelated processes and formulating an appropriate differential diagnosis. Moreover, recognizing these disease processes at imaging and contextualizing imaging findings with clinical information and laboratory and pathologic findings can facilitate definitive diagnosis and proper treatment. The authors review the articular and extra-articular thoracic imaging manifestations of RA, including cardiovascular, respiratory, and pleural diseases, as well as treatment-related complications and common infections. ©RSNA, 2021.

Multilobulated thymoma with an acute angle: a new predictor of lung invasion.

OBJECTIVE: Imaging features of thymomas such as lobulation, infiltration into lung, and adjacent lung abnormality have been associated with lung invasion but are unreliable. The goal of this study was to develop a more objective and reproducible method for predicting lung invasion by thymomas. SUBJECTS AND METHODS: Fifty-four thymomas resected from 2007 to 2017 were included for analysis. Pre-operative CT scans for these thymomas were reviewed, and multiple features were evaluated, including the interface of each thymoma with the adjacent lung. A multilobulated thymoma with at least one acute angle between lobulations was considered suspicious for lung invasion. Two blinded radiologists then tested this hypothesis by reviewing all 54 CT scans and using this single criterion to predict lung invasion. RESULTS: Twelve thymomas invaded the lung. All lung-invasive thymomas were multilobulated. Twenty-nine thymomas had a multilobulated interface with the lung. Multilobulated thymomas were more likely to invade the lung than thymomas with a single lobulation or no lobulation (p = 0.0008). Using the criterion of multilobulation with at least one acute angle between lobulations to predict lung invasion, the two readers achieved a sensitivity of 67-83%, specificity of 93-98%, positive predictive value of 77-89%, and negative predicted value of 91-95%. Nine lung-invasive thymomas also invaded mediastinal structures or disseminated to the pleura. CONCLUSIONS: A multilobulated thymoma with at least one acute angle between lobulations predicts lung invasion with a high degree of accuracy. When lung invasion is suspected, the findings are indicative of a locally aggressive tumor, and the pleura and mediastinal structures should also be closely inspected for invasion. KEY POINTS: • A multilobulated thymoma with at least one acute angle between lobulations is predictive of lung invasion. • Coronal and sagittal reformations and thin sections are helpful in challenging cases. • Lung invasion indicates a locally aggressive tumor, and the pleura and other mediastinal structures should also be closely inspected for invasion.

Screening for Lung Cancer: Communicating With Patients.

OBJECTIVE: The purposes of this article are to detail the experience of a single-center academic institution in applying the patient-centered approach to a lung cancer screening program and to examine how this approach can expand to other aspects of follow-up imaging of lung nodules. CONCLUSION: As the practice of patient-centered radiology gains attention, diagnostic radiologists are findings new ways to become more involved in patient care. A lung cancer screening program is one opportunity for radiologists to consult with and educate patients.

Dendriform Pulmonary Ossification in the Absence of Usual Interstitial Pneumonia: CT Features and Possible Association With Recurrent Acid Aspiration.

OBJECTIVE: Dendriform pulmonary ossification (DPO) is a rare lung disease in which mature bone is present in the peripheral interstitium of the lung. It typically occurs in patients with usual interstitial pneumonia (UIP). We assessed patients with CT findings of DPO without UIP to determine possible causative factors and to assess the clinical and CT course. We hypothesized that DPO without UIP would be a unique entity. MATERIALS AND METHODS: We retrospectively reviewed CT reports for the word "ossification." Two observers reviewed each examination for micronodules 1-5 mm in diameter in the peripheral interstitium (subpleural and perifissural spaces and interlobular septa), some of which had high attenuation on mediastinal windows, presence of contiguous clusters of nodules resulting in a branching pattern, and lack of findings of UIP or focal lung disease. We reviewed the electronic medical records and follow-up CT and clinical information in all eligible patients. RESULTS: The study population consisted of 52 men with a median age of 79 years old. Seventy-five percent of the patients had gastroesophageal reflux disease, obstructive sleep apnea, or a chronic neurologic disorder. No progressive pulmonary symptoms were attributed directly to DPO, and no patient developed pulmonary fibrosis or suffered clinical decline from DPO. CT showed minimal progression or remained stable at follow-up (77% for at least 1 year, 25% for over 4 years). CONCLUSION: DPO in the absence of UIP occurs in elderly men and appears to be associated with chronic aspiration of gastric acid. The course is indolent.

Imatinib Treatment of Lymphangiomatosis (Generalized Lymphatic Anomaly).

Lymphangiomatosis (eg, generalized lymphatic anomaly) is an abnormal proliferation of lymphatic endothelial cells. It is often a childhood disease, but it may present in adulthood by infiltrating organs and cause obstruction, bleeding, or disruption of lymphatic flow. Pulmonary involvement may be mild or cause diffuse interstitial lung disease, airway obstruction, hemoptysis, chylothorax, chylopericardium, and culminate in respiratory failure. Treatment has been limited to surgical resection or drainage procedures because there is no accepted effective systemic therapy. This report presents a patient with lymphangiomatosis and life-threatening hemoptysis in whom positive immunostaining forc-KITsuggested upregulation of tyrosine kinase and whose disease was controlled with imatinib.

CT in Idiopathic Pulmonary Fibrosis: Diagnosis and Beyond.

OBJECTIVE: This review focuses on recent idiopathic pulmonary fibrosis guidelines with regard to CT-based diagnosis, the limitations and potential sources of diagnostic error in their clinical application, and proposals for future guideline modification and improvement. The review also addresses the use of CT in disease monitoring, prognostic assessment, and therapeutic clinical trials. CONCLUSION: Ongoing research and clinical experience highlight the need for updating existing guidelines frequently.

Diagnosis of Usual Interstitial Pneumonitis in the Absence of Honeycombing: Evaluation of Specific CT Criteria With Clinical Follow-Up in 38 Patients.

OBJECTIVE: We sought to evaluate specific CT criteria for the diagnosis of usual interstitial pneumonitis (UIP) in the absence of honeycombing. These criteria included peripheral reticulation and lobular distortion; some upper lobe involvement, but a lower zone predominance; a heterogeneous appearance with areas of normal lung, minimal reticulation, and substantial distortion alternating throughout the study and often on an individual image; a nonsegmental distribution; and traction bronchiectasis. MATERIALS AND METHODS: We searched reports of CT studies performed between January 1, 2009, and January 1, 2012, to identify patients for whom UIP was a likely or probable diagnosis and reviewed the CT study for each case (n = 106). There were 38 patients who met all CT criteria and who also had a clinical diagnosis of idiopathic UIP (also known as idiopathic pulmonary fibrosis [IPF]) and follow-up of at least 6 months, as determined from the electronic medical record. We reviewed prior and subsequent CT examinations in this cohort. RESULTS: The median age of our patients was 80 years, and the duration of clinical follow-up was 6-104 months (mean, 38 months; median, 37 months). For all patients, a pulmonary medicine physician made a working diagnosis of IPF. Fifteen patients died from pulmonary complications, and 16 of the surviving patients had clinical or functional progression of disease. There were no instances in which the initial diagnosis was revised or reversed. CONCLUSION: Strict application of specific CT criteria may allow a specific diagnosis of UIP in the proper clinical setting in the absence of honeycombing.

Chest pain and diarrhea: a case of Campylobacter jejuni-associated myocarditis.

BACKGROUND: Diarrhea and chest pain are common symptoms in patients presenting to the emergency department (ED). However, rarely is a relationship between these two symptoms established in a single patient. OBJECTIVE: Describe a case of Campylobacter-associated myocarditis. CASE REPORT: A 43-year-old man with a history of hypertension presented to the ED with angina-like chest pain and a 3-day history of diarrhea. Electrocardiogram revealed ST-segment elevation in the lateral leads. Coronary angiogram revealed no obstructive coronary artery disease. Troponin T rose to 1.75 ng/mL. Cardiac magnetic resonance imaging showed subepicardial and mid-myocardial enhancement, particularly in the anterolateral wall and interventricular septum, consistent with a diagnosis of myocarditis. Stool studies were positive for Campylobacter jejuni. CONCLUSIONS: Campylobacter-associated myocarditis is rare, but performing the appropriate initial diagnostic testing, including stool cultures, is critical to making the diagnosis. Identifying the etiology of myocarditis as bacterial will ensure that appropriate treatment with antibiotics occurs in addition to any cardiology medications needed for supportive care.

Comparing characteristics of individuals screened for lung cancer with 2021 versus 2013 USPSTF recommendations.

We conducted a cross-sectional multi-center study to compare the demographics, clinical characteristics, and lung cancer screening (LCS) results among those eligible for LCS per 2013 vs 2021 US Preventive Services Task Force (USPSTF) recommendations. Statistical tests are two-sided, with p < .05 considered statistically significant. Among 17,702 screened individuals (85.2% 2013 Eligible, 14.8% 2021 Newly Eligible), a higher proportion of those screened per 2021 vs 2013 criteria were female (56.1% vs 48.1%, p < .0001) and non-Hispanic Black (19.3% vs 13.4%, p < .0001). The risk of developing and dying from lung cancer per 1000 was statistically significantly higher among those eligible per 2013 vs 2021 criteria. A higher proportion of LCS exams had an increased suspicion of lung cancer in the 2013 vs 2021 criteria groups. Our data suggest that, as intended, updated 2021 USPSTF recommendations are leading to a higher proportion of LCS exams among non-Hispanic Black individuals and women.

UIP diagnosed at surgical lung biopsy, 2000-2009: HRCT patterns and proposed classification system.

OBJECTIVE: High resolution CT (HRCT) is diagnostic of usual interstitial pneumonia (UIP) if honeycombing is present. However, biopsy-proven UIP also occurs in patients without honeycombing. Identification of specific HRCT patterns may enable specific diagnosis and allow more patients to enter clinical trials. Pattern may also predict prognosis. We sought to identify specific HRCT patterns in patients with biopsy-proven UIP (2000-2009) and to assess outcomes and serial change in pattern. MATERIALS AND METHODS: We reviewed the HRCT findings in 44 patients with biopsy-proven UIP and identified four distinct patterns: classic UIP (cUIP) with honeycombing, fibrosis without honeycombing (FnoH), minimal fibrosis (Fmin), and ground-glass present (GGOp). We reviewed electronic medical records for outcome information and serial HRCT examinations when available. RESULTS: The extent of fibrosis varied between patterns; findings were always heterogeneous in the cUIP and FnoH patterns. Some Fmin patients had a more homogeneous appearance. The lower lobes were predominantly affected, but upper lobe abnormalities were always present. Mortality from respiratory failure and acute exacerbations occurred regardless of pattern. Serial progression from Fmin to FnoH to cUIP occurred, although in a variable manner. Some individuals had an acute illness (GGOp) as the initial manifestation of UIP. CONCLUSION: The FnoH pattern may be diagnostic of UIP in the proper clinical setting; heterogeneity of HRCT appearance is critical and has not been previously emphasized. Grouping of patients on the basis of pattern may allow more accurate assessment of treatment effects. Further validation and study of these HRCT patterns is warranted. Histologic UIP predicts clinical course.

Coronary artery ectasia in an adult Noonan syndrome detected on coronary CT angiography.

Coronary ectasia is rare in patients with Noonan syndrome. When suspected during echocardiography more common causes including Kawasaki disease in children and atherosclerosis coronary artery disease in adults should be ruled out. Coronary CT angiogram, a non-invasive imaging tool may be preferred over conventional coronary angiogram in the initial diagnosis and monitoring the progression of coronary ectasia in such patients. Aspirin may be considered to prevent coronary thrombosis.

Practice patterns in reporting interstitial lung abnormality at a tertiary academic medical center.

PURPOSE: Interstitial lung abnormality (ILA) is a common finding on chest CTs and is associated with higher all-cause mortality. The 2020 Fleischner Society position paper standardized the terminology and definition of ILA. Despite these published guidelines, the extent to which radiologists use this term is unknown. We evaluated practice patterns for identification of ILAs among radiologists at a tertiary academic medical center. METHODS: In this retrospective review, we identified 157 radiology reports between January 1, 2010 through December 31, 2021 containing the phrase "interstitial lung abnormality" or "interstitial abnormality". After exclusions, 125 CT scans were reviewed by thoracic-trained radiologists using the sequential reading method. RESULTS: Seventy-seven (62%) patients were found to have ILA (69% subpleural fibrotic, 19% subpleural non-fibrotic, and 6% non-subpleural), nine (7%) were equivocal for ILA and 39 (31%) had no ILA. The term ILA was used exclusively by thoracic-trained radiologists except for two cases. Use of the term ILA has rapidly increased since the position paper publication (none from 2010-2017, one case in 2018, 20 cases in 2019, 41 cases in 2020, and 73 cases in 2021), and cases were typically very mild (1-25% of the lung). CONCLUSION: While there has been increased use of the term ILA among thoracic-trained radiologists, non-thoracic radiologists have essentially not begun to use the term. Almost one-third of cases labeled ILA on clinical reads were re-classified as not having ILA on research reads.

Current Imaging of Idiopathic Pulmonary Fibrosis.

The major role of imaging (CT) in usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) is in the initial diagnosis. We propose several modifications to existing guidelines to help improve the accuracy of this diagnosis and to enhance interobserver agreement. CT detects the common complications and associations that occur with UIP/IPF including acute exacerbation, lung cancer, and dendriform pulmonary ossification and is useful in informing prognosis based on baseline fibrosis severity. Serial CT imaging is a topic of great interest; it may identify disease progression before FVC decline or clinical change.

Management of Incidental Pulmonary Nodules: Influencing Patient Care Through Subspecialized Imaging Review.

OBJECTIVE: To evaluate whether thoracic radiologist review of computed tomography-detected incidental pulmonary nodules initially reported by non-thoracic imagers would change management recommendations. MATERIALS AND METHODS: The Radiology Consultation Service identified 468 computed tomography scans (one per patient) performed through the adult emergency department from August 2018 through December 2020 that mentioned the presence of a pulmonary nodule. Forty percent (186/468) were read by thoracic radiologists and 60% (282/468) were read by non-thoracic radiologists. The Radiology Consultation Service contacted all patients in order to assess risk factors for lung malignancy. Sixty-seven patients were excluded because they were unreachable, declined participation, or were actively followed by a pulmonologist or oncologist. A thoracic radiologist assessed the nodule and follow up recommendations in all remaining cases. RESULTS: A total of 215 cases were re-reviewed by thoracic radiologists. The thoracic radiologist disagreed with the initial nodule recommendations in 38% (82/215) of cases and agreed in 62% (133/215) of cases. All discordant cases resulted in a change in management by the thoracic radiologist with approximately one-third (33%, 27/82) decreasing imaging utilization and two-thirds (67%, 55/82) increasing imaging utilization. Nodules were deemed benign and follow up eliminated in 11% (9/82) of discordant cases. DISCUSSION: Our study illustrates that nodule review by thoracic radiologists results in a change in management in a large percentage of patients. Continued research is needed to determine whether subspecialty imaging review results in increased or more timely lung cancer detection.

Plexiform leiomyoma of the esophagus: a complex radiographic, pathologic and endoscopic diagnosis.

Radiographic identification of an abnormal lesion in the esophagus routinely occurs during workup of patients with symptomatic dysphagia. Leiomyoma is the most common benign finding; however, plexiform leiomyoma, a distinctive but rare variant, follows an unusual pattern of growth which can be a challenging surgical resection. A review of indexed literature identified a single previous report. We contribute a second case of plexiform leiomyoma with a discussion of the clinical, radiographic, and pathologic characteristics, as well as the differential diagnosis for plexiform lesions.

The bullseye sign: A variant of the reverse halo sign in COVID-19 pneumonia.

The predominant pulmonary imaging findings on chest CT in the novel 2019 coronavirus infection (COVID-19) are bilateral ground glass opacities. The reverse halo sign is uncommon. This is a report of the new "bullseye sign," which is considered a variant of the reverse halo sign and favored to represent a focus of organizing pneumonia. The specificity of this finding is unclear, however its presence should alert radiologists to the possibility of COVID-19 infection.