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Aim: To retrospectively assess the frequency of internal mammary lymph nodes (IMNs) in patients after mastectomy and tissue-expander reconstruction. Materials and Methods: Statistical analysis was performed for all available data in patients with mastectomy and tissue-expander reconstruction from 2004-2007 (study group). The data were compared with that of a control population with mastectomy who did not have reconstruction (control group). Patients with recurrent breast cancers, previous breast reconstruction, surgeries performed at outside hospitals, no available pre- or postoperative computed tomography (CT) or magnetic resonance imaging (MRI) data, or inadequate imaging follow-up were excluded. Results: There were eight patients in the study group (median age 50.5 years, seven breast cancers), and eight patients in the control group (median age 52 years, seven breast cancers). No patients had IMNs on their preoperative imaging examinations. New IMNs were present in postoperative imaging in seven of eight patients (7/8, 87.5%) in the study group. All of them were stable or decreased in size on subsequent imaging examinations. None of the patients in the control group had IMNs (0/8). Conclusion: IMNs are common on imaging after mastectomy and tissue-expander placement. The IMNs decreased or remained stable on follow-up imaging and may represent reactive nodes. [ABSTRACT FROM AUTHOR]

For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) with CTLA4 inhibitors and PD-1 or PD-L1 inhibitors (hereafter, PD-(L)1 inhibitors) is associated with higher rates of anti-tumour activity and immune-related toxicities, when compared with treatment with PD-(L)1 inhibitors alone. However, there are currently no validated biomarkers to identify which patients will benefit from dual ICB 1,2 . Here we show that patients with NSCLC who have mutations in the STK11 and/or KEAP1 tumour suppressor genes derived clinical benefit from dual ICB with the PD-L1 inhibitor durvalumab and the CTLA4 inhibitor tremelimumab, but not from durvalumab alone, when added to chemotherapy in the randomized phase III POSEIDON trial 3 . Unbiased genetic screens identified loss of both of these tumour suppressor genes as independent drivers of resistance to PD-(L)1 inhibition, and showed that loss of Keap1 was the strongest genomic predictor of dual ICB efficacy-a finding that was confirmed in several mouse models of Kras-driven NSCLC. In both mouse models and patients, KEAP1 and STK11 alterations were associated with an adverse tumour microenvironment, which was characterized by a preponderance of suppressive myeloid cells and the depletion of CD8 + cytotoxic T cells, but relative sparing of CD4 + effector subsets. Dual ICB potently engaged CD4 + effector cells and reprogrammed the tumour myeloid cell compartment towards inducible nitric oxide synthase (iNOS)-expressing tumoricidal phenotypes that-together with CD4 + and CD8 + T cells-contributed to anti-tumour efficacy. These data support the use of chemo-immunotherapy with dual ICB to mitigate resistance to PD-(L)1 inhibition in patients with NSCLC who have STK11 and/or KEAP1 alterations., (© 2024. The Author(s).)

Abstract: Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Although programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade in combination with platinum-doublet chemotherapy has become a mainstay of first-line treatment for advanced NSCLC, factors associated with efficacy of chemoimmunotherapy (CIT) are not well characterized., Methods: In this multicenter retrospective analysis, clinicopathologic and genomic data were collected from patients with advanced NSCLC (lacking sensitizing genomic alterations in EGFR and ALK) and evaluated with clinical outcomes to first-line CIT., Results: Among 1285 patients treated with CIT, a worsening performance status and increasing derived neutrophil-to-lymphocyte ratio in the blood were associated with a significantly reduced objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS). With increasing PD-L1 tumor proportion scores of less than 1%, 1% to 49%, 50% to 89%, and greater than or equal to 90%, there was a progressive improvement in ORR (32.7% versus 37.5% versus 51.6% versus 61.7%, p < 0.001), mPFS (5.0 versus 6.1 versus 6.8 versus 13.0 mo, p < 0.001), and generally mOS (12.9 versus 14.6 versus 34.7 versus 23.1 mo, p = 0.009), respectively. Of 789 NSCLCs with comprehensive genomic data, NSCLCs with a tumor mutational burden (TMB) greater than or equal to the 90th percentile had an improved ORR (53.5% versus 36.4%, p = 0.004), mPFS (10.8 versus 5.5 mo, p < 0.001), and mOS (29.2 versus 13.1 mo, p < 0.001), compared with those with a TMB less than the 90th percentile. In all-comers with nonsquamous NSCLC, the presence of an STK11, KEAP1, or SMARCA4 mutation was associated with significantly worse ORR, mPFS, and mOS to CIT (all p < 0.05); this was also observed in the KRAS-mutant subgroup of NSCLCs with co-occurring mutations in STK11, KEAP1, or SMARCA4 (all p < 0.05). In KRAS wild-type NSCLC, KEAP1 and SMARCA4 mutations were associated with a significantly shorter mPFS and mOS to CIT (all p < 0.05), but STK11 mutation status had no significant impact on mPFS (p = 0.16) or mOS (p = 0.38)., Conclusions: In advanced NSCLC, better patient performance status, low derived neutrophil-to-lymphocyte ratio, increasing PD-L1 expression, a very high TMB, and STK11/KEAP1/SMARCA4 wild-type status are associated with improved clinical outcomes to first-line CIT., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: STK11 and KEAP1 mutations (STK11 mutant [STK11 MUT ] and KEAP1 MUT ) are among the most often mutated genes in lung adenocarcinoma (LUAD). Although STK11 MUT has been associated with resistance to programmed death-(ligand)1 (PD-[L]1) inhibition in KRAS MUT LUAD, its impact on immunotherapy efficacy in KRAS wild-type (KRAS WT ) LUAD is currently unknown. Whether KEAP1 MUT differentially affects outcomes to PD-(L)1 inhibition in KRAS MUT and KRAS WT LUAD is also unknown., Methods: Clinicopathologic and genomic data were collected from September 2013 to September 2020 from patients with advanced LUAD at the Dana-Farber Cancer Institute/Massachusetts General Hospital cohort and the Memorial Sloan Kettering Cancer Center/MD Anderson Cancer Center cohort. Clinical outcomes to PD-(L)1 inhibition were analyzed according to KRAS, STK11, and KEAP1 mutation status in two independent cohorts. The Cancer Genome Atlas transcriptomic data were interrogated to identify differences in tumor gene expression and tumor immune cell subsets, respectively, according to KRAS/STK11 and KRAS/KEAP1 comutation status., Results: In the combined cohort (Dana-Farber Cancer Institute/Massachusetts General Hospital + Memorial Sloan Kettering Cancer Center/MD Anderson Cancer Center) of 1261 patients (median age = 61 y [range: 22-92], 708 women [56.1%], 1065 smokers [84.4%]), KRAS mutations were detected in 536 cases (42.5%), and deleterious STK11 and KEAP1 mutations were found in 20.6% (260 of 1261) and 19.2% (231 of 1202) of assessable cases, respectively. In each independent cohort and in the combined cohort, STK11 and KEAP1 mutations were associated with significantly worse progression-free (STK11 hazard ratio [HR] = 2.04, p < 0.0001; KEAP1 HR = 2.05, p < 0.0001) and overall (STK11 HR = 2.09, p < 0.0001; KEAP1 HR = 2.24, p < 0.0001) survival to immunotherapy uniquely among KRAS MUT but not KRAS WT LUADs. Gene expression ontology and immune cell enrichment analyses revealed that the presence of STK11 or KEAP1 mutations results in distinct immunophenotypes in KRAS MUT , but not in KRAS WT , lung cancers., Conclusions: STK11 and KEAP1 mutations confer worse outcomes to immunotherapy among patients with KRAS MUT but not among KRAS WT LUAD. Tumors harboring concurrent KRAS/STK11 and KRAS/KEAP1 mutations display distinct immune profiles in terms of gene expression and immune cell infiltration., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Importance: Most early lung cancers present as pulmonary nodules on imaging, but these can be easily missed on chest radiographs., Objective: To assess if a novel artificial intelligence (AI) algorithm can help detect pulmonary nodules on radiographs at different levels of detection difficulty., Design, Setting, and Participants: This diagnostic study included 100 posteroanterior chest radiograph images taken between 2000 and 2010 of adult patients from an ambulatory health care center in Germany and a lung image database in the US. Included images were selected to represent nodules with different levels of detection difficulties (from easy to difficult), and comprised both normal and nonnormal control., Exposures: All images were processed with a novel AI algorithm, the AI Rad Companion Chest X-ray. Two thoracic radiologists established the ground truth and 9 test radiologists from Germany and the US independently reviewed all images in 2 sessions (unaided and AI-aided mode) with at least a 1-month washout period., Main Outcomes and Measures: Each test radiologist recorded the presence of 5 findings (pulmonary nodules, atelectasis, consolidation, pneumothorax, and pleural effusion) and their level of confidence for detecting the individual finding on a scale of 1 to 10 (1 representing lowest confidence; 10, highest confidence). The analyzed metrics for nodules included sensitivity, specificity, accuracy, and receiver operating characteristics curve area under the curve (AUC)., Results: Images from 100 patients were included, with a mean (SD) age of 55 (20) years and including 64 men and 36 women. Mean detection accuracy across the 9 radiologists improved by 6.4% (95% CI, 2.3% to 10.6%) with AI-aided interpretation compared with unaided interpretation. Partial AUCs within the effective interval range of 0 to 0.2 false positive rate improved by 5.6% (95% CI, -1.4% to 12.0%) with AI-aided interpretation. Junior radiologists saw greater improvement in sensitivity for nodule detection with AI-aided interpretation as compared with their senior counterparts (12%; 95% CI, 4% to 19% vs 9%; 95% CI, 1% to 17%) while senior radiologists experienced similar improvement in specificity (4%; 95% CI, -2% to 9%) as compared with junior radiologists (4%; 95% CI, -3% to 5%)., Conclusions and Relevance: In this diagnostic study, an AI algorithm was associated with improved detection of pulmonary nodules on chest radiographs compared with unaided interpretation for different levels of detection difficulty and for readers with different experience.

Aim: To assess differences in qualitative and quantitative parameters of pulmonary perfusion from dual-energy computed tomography (CT) pulmonary angiography (DECT-PA) in patients with COVID-19 pneumonia with and without pulmonary embolism (PE)., Materials and Methods: This retrospective institutional review board-approved study included 74 patients (mean age 61±18 years, male:female 34:40) with COVID-19 pneumonia in two countries (one with 68 patients, and the other with six patients) who underwent DECT-PA on either dual-source (DS) or single-source (SS) multidetector CT machines. Images from DS-DECT-PA were processed to obtain virtual mono-energetic 40 keV (Mono40), material decomposition iodine (MDI) images and quantitative perfusion statistics (QPS). Two thoracic radiologists determined CT severity scores based on type and extent of pulmonary opacities, assessed presence of PE, and pulmonary parenchymal perfusion on MDI images. The QPS were calculated from the CT Lung Isolation prototype (Siemens). The correlated clinical outcomes included duration of hospital stay, intubation, SpO 2 and death. The significance of association was determined by receiver operating characteristics and analysis of variance., Results: One-fifth (20.2%, 15/74 patients) had pulmonary arterial filling defects; most filling defects were occlusive (28/44) located in the segmental and sub-segmental arteries. The parenchymal opacities were more extensive and denser (CT severity score 24±4) in patients with arterial filling defects than without filling defects (20±8; p=0.028). Ground-glass opacities demonstrated increased iodine distribution; mixed and consolidative opacities had reduced iodine on DS-DECT-PA but increased or heterogeneous iodine content on SS-DECT-PA. QPS were significantly lower in patients with low SpO 2 (p=0.003), intubation (p=0.006), and pulmonary arterial filling defects (p=0.007)., Conclusion: DECT-PA QPS correlated with clinical outcomes in COVID-19 patients., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Introduction: Lung cancer is associated with severe coronavirus disease 2019 (COVID-19) infections. Symptom overlap between COVID-19 and lung cancer may complicate diagnostic evaluation. We aimed to investigate the incidence, symptoms, differential diagnosis, and outcomes of COVID-19 in patients with lung cancer., Methods: To determine an at-risk population for COVID-19, we retrospectively identified patients with lung cancer receiving longitudinal care within a single institution in the 12 months (April 1, 2019 to March 31, 2020) immediately preceding the COVID-19 pandemic, including an "active therapy population" treated within the last 60 days of this period. Among patients subsequently referred for COVID-19 testing, we compared symptoms, laboratory values, radiographic findings, and outcomes of positive versus negative patients., Results: Between April 1, 2019 and March 31, 2020, a total of 696 patients received longitudinal care, including 406 (58%) in the active therapy population. Among 55 patients referred for COVID-19 testing, 24 (44%) were positive for COVID-19, representing a cumulative incidence of 3.4% (longitudinal population) and 1.5% (active therapy population). Compared with patients who were COVID-19 negative, those who were COVID-19 positive were more likely to have a supplemental oxygen requirement (11% versus 54%, p  = 0.005) and to have typical COVID-19 pneumonia imaging findings (5 versus 56%, p  = 0.001). Otherwise, there were no marked differences in presenting symptoms. Among patients who were COVID-19 negative, alternative etiologies included treatment-related toxicity (26%), atypical pneumonia (22%), and disease progression (22%). A total of 16 patients positive for COVID-19 (67%) required hospitalization, and seven (29%) died from COVID-related complications., Conclusions: COVID-19 was infrequent in this lung cancer population, but these patients experienced high rates of morbidity and mortality. Oncologists should maintain a low threshold for COVID-19 testing in patients with lung cancer presenting with acute symptoms., (© 2020 The Authors.)

Objective: To determine whether dual-energy computed tomography (DECT) of the chest can be performed at a reduced radiation dose, with an emphasis on images generated with post-processing techniques., Materials and Methods: In 21 patients undergoing DECT of the chest in a dual-source scanner, an additional image series was acquired at a reduced radiation dose. Four thoracic radiologists assessed both image series for image quality, normal thoracic structures, as well as pulmonary and mediastinal abnormalities, on virtual monochromatic images at 40 keV and 60 keV. Data were analyzed with Student's t-test, kappa statistics, analysis of variance, and the Wilcoxon signed-rank test., Results: The overall image quality of 60 keV virtual monochromatic images at a reduced radiation dose was considered optimal in all patients, and no abnormalities were missed. Contrast enhancement and lesion detection performance were comparable between reduced-dose images at 40 keV and standard-of-care images at 60 keV. The intraobserver and interobserver agreement were both good. The mean volumetric CT dose index (CTDIvol), size-specific dose estimate (SSDE), dose-length product (DLP), and effective dose (ED) for reduced-dose DECT were 3.0 ± 0.6 mGy, 4.0 ± 0.6 mGy, 107 ± 30 mGy.cm, and 1.5 ± 0.4 mSv, respectively., Conclusion: DECT of the chest can be performed at a reduced radiation dose (CTDIvol < 3 mGy) without loss of diagnostic information.

Objective: To assess the image quality of chest CT reconstructed with image-based iterative reconstruction (SafeCT; MedicVision ® , Tirat Carmel, Israel), adaptive statistical iterative reconstruction (ASIR; GE Healthcare, Waukesha, WI) and model-based iterative reconstruction (MBIR; GE Healthcare, Waukesha, WI) techniques at CT dose index volume (CTDI vol ) <1 mGy., Methods: In an institutional review board-approved study, 25 patients gave written informed consent for acquisition of three reduced dose (0.25-, 0.4- and 0.8-mGy) chest CT after standard of care CT (8 mGy) on a 64-channel multidetector CT (MDCT) and reconstructed with SafeCT, ASIR and MBIR. Two board-certified thoracic radiologists evaluated images from the lowest to the highest dose of the reduced dose CT series and subsequently for standard of care CT., Results: Out of the 182 detected lesions, the missed lesions were 35 at 0.25, 24 at 0.4 and 9 at 0.8 mGy with SafeCT, ASIR and MBIR, respectively. The most missed lesions were non-calcified lung nodules (NCLNs) 25/112 (<5 mm) at 0.25, 18/112 (<5 mm) at 0.4 and 3/112 (<4 mm) at 0.8 mGy. There were 78%, 84% and 97% lung nodules detected at 0.25, 0.4 and 0.8 mGy, respectively regardless of iterative reconstruction techniques (IRTs), Most mediastinum structures were not sufficiently seen at 0.25-0.8 mGy., Conclusion: NCLNs can be missed in chest CT at CTDI vol of <1 mGy (0.25, 0.4 and 0.8 mGy) regardless of IRTs. The most lung nodules (97%) were detected at CTDI vol of 0.8 mGy. The most mediastinum structures were not sufficiently seen at 0.25-0.8 mGy. Advances in knowledge: NCLNs can be missed regardless of IRTs in chest CT at CTDI vol of <1 mGy. The performance of ASIR, SafeCT and MBIR was similar for lung nodule detection at 0.25, 0.4 and 0.8 mGy.

Cardiothoracic diseases result in substantial morbidity and mortality. Chest computed tomography (CT) has been an imaging modality of choice for assessing a host of chest diseases, and technologic advances have enabled the emergence of coronary CT angiography as a robust noninvasive test for cardiac imaging. Technologic developments in CT have also enabled the application of dual-energy CT scanning for assessing pulmonary vascular and neoplastic processes. Concerns over increasing radiation dose from CT scanning are being addressed with introduction of more dose-efficient wide-area detector arrays and iterative reconstruction techniques. This review article discusses the technologic innovations in CT and their effect on cardiothoracic applications.

Advanced, anaplastic lymphoma kinase (ALK)-positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors (e.g., ceritinib and alectinib) upon progression. Second-generation inhibitors are generally effective even in the absence of crizotinib-resistant ALK mutations, likely reflecting incomplete inhibition of ALK by crizotinib in many cases. Herein, we analyzed 103 repeat biopsies from ALK-positive patients progressing on various ALK inhibitors. We find that each ALK inhibitor is associated with a distinct spectrum of ALK resistance mutations and that the frequency of one mutation, ALK G1202R , increases significantly after treatment with second-generation agents. To investigate strategies to overcome resistance to second-generation ALK inhibitors, we examine the activity of the third-generation ALK inhibitor lorlatinib in a series of ceritinib-resistant, patient-derived cell lines, and observe that the presence of ALK resistance mutations is highly predictive for sensitivity to lorlatinib, whereas those cell lines without ALK mutations are resistant., Significance: Secondary ALK mutations are a common resistance mechanism to second-generation ALK inhibitors and predict for sensitivity to the third-generation ALK inhibitor lorlatinib. These findings highlight the importance of repeat biopsies and genotyping following disease progression on targeted therapies, particularly second-generation ALK inhibitors. Cancer Discov; 6(10); 1118-33. ©2016 AACRSee related commentary by Qiao and Lovly, p. 1084This article is highlighted in the In This Issue feature, p. 1069., (©2016 American Association for Cancer Research.)

Purpose: PD-1 inhibitors are established agents in the management of non-small cell lung cancer (NSCLC); however, only a subset of patients derives clinical benefit. To determine the activity of PD-1/PD-L1 inhibitors within clinically relevant molecular subgroups, we retrospectively evaluated response patterns among EGFR-mutant, anaplastic lymphoma kinase (ALK)-positive, and EGFR wild-type/ALK-negative patients., Experimental Design: We identified 58 patients treated with PD-1/PD-L1 inhibitors. Objective response rates (ORR) were assessed using RECIST v1.1. PD-L1 expression and CD8(+) tumor-infiltrating lymphocytes (TIL) were evaluated by IHC., Results: Objective responses were observed in 1 of 28 (3.6%) EGFR-mutant or ALK-positive patients versus 7 of 30 (23.3%) EGFR wild-type and ALK-negative/unknown patients (P = 0.053). The ORR among never- or light- (≤10 pack years) smokers was 4.2% versus 20.6% among heavy smokers (P = 0.123). In an independent cohort of advanced EGFR-mutant (N = 68) and ALK-positive (N = 27) patients, PD-L1 expression was observed in 24%/16%/11% and 63%/47%/26% of pre-tyrosine kinase inhibitor (TKI) biopsies using cutoffs of ≥1%, ≥5%, and ≥50% tumor cell staining, respectively. Among EGFR-mutant patients with paired, pre- and post-TKI-resistant biopsies (N = 57), PD-L1 expression levels changed after resistance in 16 (28%) patients. Concurrent PD-L1 expression (≥5%) and high levels of CD8(+) TILs (grade ≥2) were observed in only 1 pretreatment (2.1%) and 5 resistant (11.6%) EGFR-mutant specimens and was not observed in any ALK-positive, pre- or post-TKI specimens., Conclusions: NSCLCs harboring EGFR mutations or ALK rearrangements are associated with low ORRs to PD-1/PD-L1 inhibitors. Low rates of concurrent PD-L1 expression and CD8(+) TILs within the tumor microenvironment may underlie these clinical observations. Clin Cancer Res; 22(18); 4585-93. ©2016 AACRSee related commentary by Gettinger and Politi, p. 4539., (©2016 American Association for Cancer Research.)

We report the case of a 47-year-old woman whose primary mediastinal leiomyoma was incidentally found during evaluation of her persistent cough. The preoperative diagnosis of mediastinal leiomyoma is challenging because of its rarity and indeterminate features on chest radiography, computed tomography (CT), and positron emission tomography-CT. We highlight how magnetic resonance imaging can substantially contribute to mediastinal mass characterization and diagnostic specificity., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Rociletinib is a third-generation EGFR inhibitor active in lung cancers with T790M, the gatekeeper mutation underlying most first-generation EGFR drug resistance. We biopsied patients at rociletinib progression to explore resistance mechanisms. Among 12 patients with T790M-positive cancers at rociletinib initiation, six had T790-wild-type rociletinib-resistant biopsies. Two T790-wild-type cancers underwent small cell lung cancer transformation; three T790M-positive cancers acquired EGFR amplification. We documented T790-wild-type and T790M-positive clones coexisting within a single pre-rociletinib biopsy. The pretreatment fraction of T790M-positive cells affected response to rociletinib. Longitudinal circulating tumor DNA (ctDNA) analysis revealed an increase in plasma EGFR-activating mutation, and T790M heralded rociletinib resistance in some patients, whereas in others the activating mutation increased but T790M remained suppressed. Together, these findings demonstrate the role of tumor heterogeneity when therapies targeting a singular resistance mechanism are used. To further improve outcomes, combination regimens that also target T790-wild-type clones are required., Significance: This report documents that half of T790M-positive EGFR-mutant lung cancers treated with rociletinib are T790-wild-type upon progression, suggesting that T790-wild-type clones can emerge as the dominant source of resistance. We show that tumor heterogeneity has important clinical implications and that plasma ctDNA analyses can sometimes predict emerging resistance mechanisms., (©2015 American Association for Cancer Research.)

Purpose: To assess lesion detection and diagnostic image quality of filtered back projection (FBP) reconstruction technique in ultra low-dose chest CT examinations., Methods and Materials: In this IRB-approved ongoing prospective clinical study, 116 CT-image-series at four different radiation-doses were performed for 29 patients (age, 57-87 years; F:M - 15:12; BMI 16-32 kg/m(2)). All patients provided written-informed-consent for the acquisitions of additional ultra low-dose (ULD) series on a 256-slice MDCT (iCT, Philips Healthcare). In-addition to their clinical standard-dose chest CT (SD, 120 kV mean CTDIvol, 6 ± 1 mGy), ULD-CT was subsequently performed at three-dose-levels (0.9 mGy [120 kV]; 0.5 mGy [100 kV] and 0.2 mGy [80 kV]). Images were reconstructed with FBP (2.5mm 1.25 mm) resulting into four-stacks: SD-FBP (reference-standard), FBP0.9, FBP0.5, and FBP0.2. Four thoracic-radiologists from two-teaching-hospitals independently-evaluated data for lesion-detection and visibility-of-small-structures. Friedman's-non-parametric-test with post hoc Dunn's-test was used for data-analysis., Results: Interobserver-agreement was substantial between radiologists (k=0.6-0.8). With pooled analysis, 146-pulmonary (27-groundglass-opacities, 64-solid-lung-nodules, 7-consolidations, 27-emphysema) and 347-mediastinal/soft tissue lesions (87-mediastinal, 46-hilar, 62-axillary-lymph-nodes, and 11-mediastinal-masses) were evaluated. Compared to the SD-FBP, 100% pulmonary-lesions were seen with FBP0.9, up to 81% with FBP0.5 (missed: 4), and up to 30% with FBP0.2 images (missed:16). Compared to SD-FBP, all enlarged mediastinal-lymph-nodes were seen with FBP0.9 images. All mediastinal-masses (>2 cm, 11/11) were seen equivalent to SD-FBP images at 0.9 mGy. Across all sizes of patients, FBP0.9 images had optimal visualization for lung findings. They were optimal for mediastinal soft tissues for only non-obese patients., Conclusion: Filtered-back-projection technique allows optimal lesion detection and acceptable image quality for chest-CT examinations at CDTIvol of 0.9 mGy for lung and mediastinal findings in selected sizes of patients., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: The purpose of this study was to compare submillisievert chest CT images reconstructed with filtered back projection (FBP), SafeCT, adaptive statistical iterative reconstruction (ASIR), and model-based iterative reconstruction (MBIR) with standard of care FBP images., Subjects and Methods: Fifty patients (33 men and 17 women; mean age [± SD], 62 ± 10 years) undergoing routine chest CT gave written informed consent for acquisition of an additional submillisievert chest CT series with reduced tube current but identical scanning length as standard of care chest CT. Sinogram data of the submillisievert series were reconstructed with FBP, SafeCT, ASIR, and MBIR and compared with FBP images at standard-dose chest CT (n = 8 × 50 = 400 series). Two thoracic radiologists performed independent comparison for visualization of lesion margin, visibility of small structures, and diagnostic acceptability. Objective noise measurements and noise spectral density were obtained., Results: Of 287 detected lesions, 162 were less than 1-cm noncalcified nodules. Lesion margins were well seen on all submillisievert reconstruction images except MBIR, on which they were poorly visualized. Likewise, only submillisievert MBIR images were suboptimal for visibility of normal structures, such as pulmonary vessels in the outer 2 cm of the lung, interlobular fissures, and subsegmental bronchial walls. MBIR had the lowest image noise compared with other techniques., Conclusion: FBP, SafeCT, ASIR, and MBIR can enable optimal lesion evaluation on chest CT acquired at a volume CT dose index of 2 mGy. However, all submillisievert reconstruction techniques were suboptimal for visualization of mediastinal structures. Submillisievert MBIR images were suboptimal for visibility of normal lung structures despite showing lower image noise.

OBJECTIVE. The purpose of this study is to compare sinogram-affirmed iterative reconstruction (SAFIRE) and filtered back projection (FBP) reconstruction of chest CT acquired with 65% radiation dose reduction. MATERIALS AND METHODS. In this prospective study involving 24 patients (11 women and 13 men; mean [± SD] age, 66 ± 10 years), two scan series were acquired using 100 and 40 Quality Reference mAs over a 10-cm scan length in the chest with a 128-MDCT scanner. The 40 Quality Reference mAs CT projection data were reconstructed with FBP and four settings of SAFIRE (S1, S2, S3, and S4). Six image datasets (FBP with 100 and 40 Quality Reference mAs, and S1, S2, S3, S4 with 40 Quality Reference mAs) were displayed on a DICOM-compliant 55-inch 2-megapixel monitor for blinded evaluation by two thoracic radiologists for number and location of lesions, lesion size, lesion margins, visibility of small structures and fissures, and diagnostic confidence. Objective noise and CT values were measured in thoracic aorta for each image series, and the noise power spectrum was assessed. Data were analyzed with analysis of variance and Wilcoxon signed rank tests. RESULTS. All 186 lesions were seen on 40 Quality Reference mAs SAFIRE images. Diagnostic confidence on SAFIRE images was higher than that for FBP images. Except for the minor blotchy appearance on SAFIRE settings S3 and S4, no significant artifacts were noted. Objective noise with 40 Quality Reference mAs S1 images (21.1 ± 6.1 SD of HU) was significantly lower than that for 40 Quality Reference mAs FBP images (28.5 ± 8.1 SD of HU) (p < 0.001). Noise power spectra were identical for SAFIRE and FBP with progressive noise reduction with higher iteration SAFIRE settings. CONCLUSION. Iterative reconstruction (SAFIRE) allows reducing the radiation exposure by approximately 65% without losing diagnostic information in chest CT.

Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer has an oncogene-addicted biology that confers sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Published data suggest that EGFR addiction persists after development of TKI acquired resistance, leading many clinicians to continue TKI with subsequent chemotherapy; however, this strategy has not been formally evaluated. Methods. We retrospectively reviewed an institutional database to identify patients with advanced EGFR mutation with acquired resistance who subsequently received chemotherapy. Patients were classified as receiving chemotherapy with continued erlotinib or chemotherapy alone. We assessed differences in outcomes between the two strategies. Results. Seventy-eight patients were included, 34 treated with chemotherapy and erlotinib and 44 treated with chemotherapy alone. Objective response rate was evaluable in 57 patients and was 41% for those treated with chemotherapy and erlotinib and 18% for those treated with chemotherapy alone. After adjusting for chemotherapy regimen and length of initial TKI course, the odds ratio for the response rate was 0.20 (95% confidence interval: 0.05-0.78; p = .02) favoring treatment with chemotherapy and erlotinib. The median progression-free survival was 4.4 months on chemotherapy and erlotinib and 4.2 months on chemotherapy alone (adjusted hazard ratio = 0.79; 95% confidence interval: 0.48-1.29; p = .34). There was no difference in overall survival. Conclusion. This is the first study, to our knowledge, to demonstrate that continuation of EGFR TKI with chemotherapy in patients with acquired resistance improves outcomes compared with chemotherapy alone. We observed an improved response rate but no difference in progression-free survival or overall survival. A larger prospective clinical trial is needed to evaluate this promising strategy further.

Objective. Talc pleurodesis is a common procedure performed to treat complications related to lung cancer. The purpose of our study was to characterize any thoracic nodal findings on FDG PET/CT associated with prior talc pleurodesis. Materials and Methods. The electronic medical record identified 44 patients who underwent PET/CT between January 2006 and December 2010 and had a history of talc pleurodesis. For each exam, we evaluated the distribution pattern, size, and attenuation of intrathoracic lymph nodes and the associated standardized uptake value. Results. High-attenuation intrathoracic lymph nodes were noted in 11 patients (25%), and all had corresponding increased FDG uptake (range 2-9 mm). Involved nodal groups were anterior peridiaphragmatic (100%), paracardiac (45%), internal mammary (25%), and peri-IVC (18%) nodal stations. Seven of the 11 patients (63%) had involvement of multiple lymph nodal groups. Mean longitudinal PET/CT and standalone CT followups of 15 ± 11 months showed persistence of both high-attenuation and increased uptake at these sites, without increase in nodal size suggesting metastatic disease involvement. Conclusions. FDG avid, high-attenuation lymph nodes along the lymphatic drainage pathway for parietal pleura are a relatively common finding following talc pleurodesis and should not be mistaken for nodal metastases during the evaluation of patients with history of lung cancer.

Hypersensitivity pneumonitis is an inflammatory lung disease that develops in response to exposure to antigen. Cases can be stratified by the duration of exposure and speed of symptom progression into acute, subacute, and chronic hypersensitivity pneumonitis. Although the pathologic features of subacute hypersensitivity pneumonitis are well established and those of chronic hypersensitivity pneumonitis have been reported, little is known about the histopathology of acute hypersensitivity pneumonitis. We evaluated the pathologic features of 5 patients with clinically confirmed hypersensitivity pneumonitis and rapid onset of symptoms and 3 patients with subacute or chronic hypersensitivity pneumonitis with symptom exacerbation. Histopathologic features assessed in each case included those characteristic of subacute hypersensitivity pneumonitis (bronchiolocentric chronic inflammation, histiocytic aggregates, and bronchiolitis obliterans), those associated with acute inflammation (fibrin deposition and neutrophilic infiltrate), and fibrosis. The classic features of hypersensitivity pneumonitis were identified in all 8 cases, with 1 also exhibiting fixed fibrosis confirming underlying chronic hypersensitivity pneumonitis. Fibrin deposition was present in 8 (100%) of 8 cases, and its extent was significant (28% surface area fibrin deposition/total disease area on average). Two had intra-alveolar fibrin so marked that it resembled acute fibrinous and organizing pneumonia. In addition, prominent interstitial neutrophilic infiltrate (≥5 cells/high-power field) was seen in all cases. These features have not been reported as characteristics of subacute or chronic hypersensitivity pneumonitis. Increased fibrin deposition and neutrophilic infiltrate may characterize acute hypersensitivity pneumonitis or abrupt exacerbation of hypersensitivity pneumonitis, and these along with characteristic features of subacute hypersensitivity pneumonitis (granulomatous inflammation and bronchiolocentricity) are sufficient to establish a morphologic diagnosis, particularly in conjunction with clinicoradiologic features., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the spectrum of urgent findings on portable chest radiography.