T cells, particularly those producing IL-4, are implicated in inflammation-mediated fibrosis. In our phase I/IIa open-label pilot study in 15 patients with scleroderma-interstitial lung disease (SSc-ILD), high-dose imatinib treatment showed modest improvement in lung function and skin score, but with several adverse events. Here, we investigated T cell phenotype and cytokine production in bronchoalveolar lavage (BAL) from patients enrolled in this trial. We found that IL-4⁺ T cells showed a stronger correlation with ground glass opacity (GGO) than fibrosis scores on lung high-resolution computer tomography scans. Frequencies of IL-4⁺ T cells also discriminated patients with high (≥ 20) versus low (< 20) GGO scores. Functional annotation clustering of proteins that correlated with T cells identified two major clusters that belonged to immune/inflammatory and wounding response. Repeat analyses after 1 year of treatment in 10 BAL samples, one each from the right middle and lower lobes of lung from 5 patients, showed that post-imatinib, IL-4⁺ T cells were profoundly reduced but CD4⁺ T cells increased, except in one patient who showed worsening of SSc-ILD. Post-imatinib increase in CD4⁺ T cells correlated with soluble ICAM-3 and PECAM-1 levels in BAL, which associated with the lack of worsening in SSc-ILD. Thus, imatinib might confer its therapeutic effect in fibrosis via re-directing T cell responses from type 2 to other, non-type 2 cytokine producing CD4⁺ T cells.

The Scleroderma Lung Study showed the efficacy of cyclophosphamide in modestly improving the forced vital capacity (FVC) compared with placebo over 1 year. Using changes in texture-based scores that quantify lung fibrosis as the percentage involvement of reticulation patterns, the effectiveness of cyclophosphamide was re-assessed by examining its impact on quantitative lung fibrosis (QLF). Axial HRCT images were acquired (1-mm slice thickness, 10-mm increments) in the prone position at inspiration. A validated model for quantifying interstitial disease patterns was applied to images from 83 subjects at baseline and 12 months. Scores were calculated for six zones (upper, mid, lower of the right/left lung) and the whole lung. Average changes were compared. Correlations were performed between QLF and physiological and clinical scores.

The objective of our study was to determine the distribution of effective dose associated with a single low-dose CT chest examination of average-size participants in the National Lung Screening Trial. Organ doses were also investigated. Thirty-three sites nationwide provided volume CT dose index (CTDIvol) data annually for the 97 MDCT scanners used to image 26,724 participants during the trial. The dose data were representative of the imaging protocols used by the sites for average-size participants. Effective doses were estimated first using the product of the dose-length product (CTDIvol 35-cm scan length) and a published conversion factor, k. The commercial software product CT-Expo was then used to estimate organ doses to males and females from the average CTDIvol. Applying tissue-weighting factors from both publication 60 and the more recent publication 103 of the International Commission on Radiological Protection (ICRP) allowed comparisons of effective doses to males and to females.

Randomized controlled trials (RCTs) evaluating cancer screening modalities usually employ cause-specific mortality as their primary endpoint. Because death certificate cause of death can be inaccurate, RCTs frequently use review committees to assign an underlying cause of death. We describe the National Lung Screening Trial's (NLST's) death review approach, the Endpoint Verification Process (EVP), which strives to minimize errors in assignment of cause of death due to lung cancer. Deaths selected for review include those with a notation of lung cancer on the death certificate and those occurring among participants ever diagnosed with lung cancer. Other criteria that trigger death review include, but are not limited to, death within 6months of a screen suspicious for lung cancer and death within 60days of certain diagnostic evaluation procedures associated with a screen suspicious for lung cancer or a lung cancer diagnosis. EVP requires concordance on whether death was due to lung cancer. Deaths are first reviewed by the EVP chair. If concordance is not achieved, the death is next reviewed by an Endpoint Verification Team (EVT) member. If concordance between the chair- and member-assigned cause of death is not achieved, the death is next reviewed by a group of at least three EVT members. Cause of death is assigned at the step in which concordance was achieved, or if necessary, at the team review.

Patients with systemic sclerosisassociated interstitial lung disease (SSc-ILD) are thought to have the greatest decline in lung function (forced vital capacity [FVC] % predicted) in the early years after disease onset. The aim of this study was to assess the natural history of the decline in FVC % predicted in patients receiving placebo in the Scleroderma Lung Study and to evaluate possible factors for cohort enrichment in future therapeutic trials. Patients randomized to receive placebo (n = 79) were divided into 3 groups based on the duration of SSc (02 years, 24 years, and >4 years). Descriptive statistics and a mixed-effects model were used to analyze the rate of decline in the FVC % predicted over a 1-year period. Additional analyses stratified according to the severity of fibrosis on high-resolution computed tomography (HRCT) were performed, and interactions between disease severity and disease duration were explored.

After long debate about the worth of screening for lung cancer, and even about the merits of doing a randomized trial to address the issue, initial results from the first large-scale randomized controlled trial ever to show a reduction in lung cancer mortality associated with screening were announced to the public last November 4.1 The story behind this historical first is informative, and the editor of the Journal of Medical Screening played a role in that story. But more of that later.

The objective of this study is to identify baseline characteristics of patients with scleroderma-related interstitial lung disease (SSc-ILD) that could serve as predictors of the most favorable response to 12-month treatment with oral cyclophosphamide (CYC). Regression analyses were retrospectively applied to the Scleroderma Lung Study data in order to identify baseline characteristics that correlated with the absolute change in forced vital capacity (FVC) (% predicted values) and the placebo-adjusted change in % predicted FVC over time (the CYC treatment effect).

The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009...

Ample studies suggest that the cyclooxygenase-2 (COX-2) / prostaglandin E2 (PGE2) pathway plays a pivotal role in carcinogenesis and that COX-2 inhibition may help prevent lung cancer. Therefore, we conducted a randomized, double-blind, placebo-controlled trial of the COX-2selective inhibitor celecoxib (400 mg bid for 6 months) in former-smokers (age 45, 30 pack-years of smoking, 1 year of sustained abstinence from smoking). We assessed the impact of celecoxib on cellular and molecular events associated with lung cancer pathogenesis; the primary endpoint was bronchial Ki-67 labeling index (Ki-67 LI) after 6 months of treatment. Of 137 randomized subjects, 101 completed both baseline and 6-month bronchoscopies and were evaluable for the primary endpoint analysis. The beneficial effect on Ki-67 LI was greater in the celecoxib arm (versus placebo) in a mixed-effects analysis (P = 0.0006), and celecoxib significantly decreased Ki-67 LI by an average of 34%, whereas placebo increased Ki-67 LI by an average of 3.8% (P = 0.04; t test). In participants who crossed over to the other study arm at 6 months (all of whom had received 6 months of celecoxib at the end of a 12 months treatment period), the decreases in Ki-67 LI correlated with a reduction and/or resolution of lung nodules on computed tomography. Celecoxib significantly reduced plasma c-reactive protein and interleukin-6 mRNA and protein and increased 15(S)-hydroxy-eicosatetraenoic acid levels in bronchoalveolar lavage (BAL) samples. The baseline ratio of COX-2 to 15-hydroxyprostaglandin dehydrogenase mRNA in BAL cells was a significant predictive marker of Ki-67 response to celecoxib (P = 0.002). Our collective findings support the continued investigation of celecoxib for lung cancer chemoprevention in former smokers at a low risk of cardiovascular disease.

Accurate staging of lung cancer is necessary to describe and communicate disease extent, predict prognosis, determine therapy, and evaluate the results of clinical trials. The Union Internationale Contre le Cancer and the American Joint Committee on Cancer published the seventh edition of tumor, node, and metastasis in lung cancer in 2009. Changes to the sixth edition have been based on the analysis of a large database of patients with lung cancer by the International Staging Committee of the International Association for the Study of Lung Cancer. This study reviews the new seventh edition of the tumor, node, and metastasis lung cancer staging system and discusses the radiologic and therapeutic implications.

Acute respiratory illness is defined as one or more of the following: cough, sputum production, chest pain, or dyspnea (with or without fever). The workup of these patients depends on many factors, including clinical presentation and the suspected etiology. This study reviews the literature on the indications and usefulness of radiologic studies for the evaluation of acute respiratory illness in the immuno- competent patient. The following recommendations are the result of evidence-based consensus by the American College of Radiology Appropriateness Criteria Expert Panel on Thoracic Radiology. Chest radiographs are usually appropriate in (1) patients with positive physical examination or risk factors for pneumonia, (2) for the assessment of complicated pneumonia, or (3) in cases of emerging infections and biological warfare agents such as severe acute respiratory syndrome, H1N1, and anthrax. Computed tomography, although having a more limited role, is usually appropriate (1) in the assessment of complicated pneumonia and (2) in patients with suspected severe acute respiratory syndrome, H1N1, or anthrax and a normal radiograph.

Pretreatment ADC histogram analysis can stratify progression- free survival in bevacizumab-treated patients with newly diagnosed GBM. Lower ADC is associated with tumor MGMT promoter methylation, which may, in part, account for the favorable outcome associated with low ADC_L tumors.

Strategic efforts were associated with significant increases in minority enrollment. The greatest successes require that a priori goals be established based on eligible racial/ethnic proportions; the historical performance of sites in minority accrual should factor into the selection of sites; recruitment planning must begin well in advance of trial launch; and there must be endorsement by prominent representatives of the racial groups of interest.

Screening for pulmonary metastatic disease is an important step for staging a patient with a known or recently discovered malignancy. Here we present our recommendations for screening for metastatic disease based on recommendations from the literature and experiences of pulmonary radiologists. In short, chest computed tomographic (CT) screening is the most appropriate tool for evaluation of pulmonary metastasis in the majority of cases. Chest computed tomographic screening is also recommended for follow-up and to determine response to therapy. Other modalities such as chest radiography, magnetic resonance imaging, and scintigraphy will also be discussed. Please note that this study is a summary of the complete version of this topic, which is available on the ACR website at www.acr.org. Practitioners are encouraged to refer to the complete version.

Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multi- disciplinary strategic management of tissue for molecular and immunohistochemical studies.

Nonsurgical management of early primary lung cancer has grown tremendously in recent years, and today, available options extend far beyond that of conventional radiation therapy (CRT) to include minimally invasive image-guided delivery of thermal energies, specifically radiofrequency ablation, microwave ablation, and cryoablation, and more conformal stereotactic body radiation therapy. Because the tumor is never resected with these nonoperative interventions, histopathological evaluation of tumor margins for the presence of residual tumor is impossible, and as such, tumor response after each of these therapies is largely based on imaging. To date, computerized tomography and computerized tomography-positron emission tomography remain the most readily available modalities for assessment of therapeutic efficacy, and to this end as detailed within this article, strict imaging survey and familiarity with the expected imaging characteristics of the treated tumor will aid in recognition of unexpected findings, specifically those of incomplete therapy and/or tumor recurrence.

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented.