Use Of Low-dose Computed Tomography Research Articles

Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality.

Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality.

Baseline computed tomography screening and blood microRNA predict lung cancer risk and define adequate intervals in the BioMILD trial

Large randomized trials have demonstrated that lung cancer (LC) screening with low-dose computed tomography (LDCT) reduces LC mortality in heavy smokers. We previously showed in the MILD screening trial that the combination of a prespecified circulating microRNA (miRNA) signature classifier (MSC) and LDCT improves the accuracy of LDCT alone. The primary aim of the prospective BioMILD study was to assess the additional value of the blood MSC assay at the time of baseline LDCT with the goal of personalizing LC screening intervals. The study enrolled 4119 volunteers from January 2013 to March 2016, with a median follow-up of 5.3 years. Baseline LDCT and miRNAs stratified participants into four groups: CT-/MSC- (n= 2664; 64.7%); CT-/MSC+ (n= 800; 19.4%); CT+/MSC- (n= 446; 10.8%); and CT+/MSC+ (n= 209; 5.1%). As per the protocol, those in the CT-/MSC- and CT-/MSC+ groups were allocated to LDCT repeat at 3-year and 1-year intervals; CT+ participants were allocated for 1-year or earlier intervals on the basis of LDCT features independent of MSC results. CT+ participants had a 15.8-fold higher 4-year LC incidence than CT- participants (95% confidence interval 10.34-24.05), and MSC+ participants had a 2.0-fold higher 4-year LC incidence than MSC- participants (95% confidence interval 1.40-2.90); there was no evidence that the MSC effect differed between CT+ and CT- participants. LC incidence at 4 years was 0.8% in CT-/MSC-, 1.1% in CT-/MSC+, 10.8% in CT+/MSC-, and 20.1% in CT+/MSC+ participants. LC mortality rates at 5 years in the four risk groups were 0.5 in CT-/MSC-, 1.5 in CT-/MSC+, 4.2 in CT+/MSC-, and 10.1 in CT+/MSC+. The combined use of LDCT and blood miRNAs at baseline predicts individual LC incidence and mortality, with a major effect of MSC for LDCT-positive individuals. These findings may have important implications in personalizing screening intervals.

Expanding the Utilization of Low-Dose Computed Tomography in Plastic and Reconstructive Surgery Based on Validated Practices Among Surgical Specialties.

As computed tomography (CT) usage increases, so have concerns over radiation-induced malignancy. To mitigate these risks, low-dose CT (LDCT) has emerged as a versatile alternative by other specialties, although its use in plastic surgery remains sparse. This study aimed to investigate validated uses of LDCT across surgical specialties and extrapolate these insights to expand its application for plastic surgeons. A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using search terms "low dose CT" OR "low dose computed tomography" AND "surgery," where the name of each surgical specialty was substituted for word "surgery" and each specialty term was searched separately in combination with the 2 CT terms. Data on radiation dose, outcomes, and level of evidence were collected. Validated surgical applications were correlated with similar procedures and diagnostic tests performed routinely by plastic surgeons to extrapolate potential applications for plastic surgeons. A total of 3505 articles were identified across surgical specialties, with 27 ultimately included. Depending on the application, use of LDCT led to a 25% to 97% reduction in radiation dose and all studies reported noninferior image quality and diagnostic capability compared with standard-dose CT. Potential identified uses included the following: evaluation of soft tissue infections, preoperative and postoperative management of facial and hand fractures, flap design, 3D modeling, and surgical planning. Low-dose CT is a valid imaging alternative to standard-dose CT. Expanded utilization in plastic surgery should be considered to minimize the iatrogenic effects of radiation and to promote patient safety without compromising outcomes.

Assessment and Efficacy of Low-Dose CT Screening and Primary Care Providers Perspective on Lung Cancer Screening: An Institutional Review.

Lung cancer is the most common cause of death in both men and women. The United States Preventive Services Task Force (USPSTF) recommends annual lung screening with low-dose computed tomography (LDCT) chest for individuals aged 55-80 who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. We reviewed the electronic medical records of patients visiting our outpatient clinic over a period of one year. We included all eligible individuals according to USPSTF guidelines for LDCT to identify screening rates at our institution. All primary care physicians, including residents and attendings, were given a prepared questionnaire to understand their beliefs and concerns with the implementation of this program. A total of 13,500 patients visited the outpatient clinic and 1178 were eligible for LDCT. Forty-five percent (45%) of patients received LDCT screening, which was higher than the national average of 2%-5%. A total of 50 primary care providers were included in the survey. The majority of the providers were aware of the USPSTF guidelines and believed that patients with multiple comorbidities and insurance issues were barriers in initiating LDCT screening. Lung cancer screening is an important component in cancer preventive strategies. Widespread awareness among the primary care providers and the public is extremely necessary for improving the use of LDCT.

A narrative review of lung cancer screening in underserved populations

: Lung cancer screening with low-dose computed tomography (LDCT) is an effective approach for the early detection of lung cancer and the reduction of lung cancer specific mortality in high risk individuals. Despite recommendations for LDCT screening by the National Comprehensive Cancer Network (NCCN) and the United States Preventive Services Task Force, the utilization of LDCT screening in clinical practice has been low. Moreover, significant disparities in the use of LDCT have been described in underserved populations, including African American or black patients, rural patients with limited access to LDCT screening facilities, and other vulnerable patient groups with known risk factors for developing lung cancer. Several patient, provider, and healthcare systems level approaches have been proposed to mitigate lung cancer screening disparities. Such approaches include raising awareness of LDCT screening benefits and the evidence in support of LDCT screening among healthcare providers, educating patients on LDCT screening and optimizing shared decision-making approaches between patients and providers, and expanding patient access to LDCT screening through free and mobile lung cancer screening programs. As lung cancer screening utilization continues to expand in clinical practice, it will be critical to continue investigating the trends, causes, and outcomes of LDCT screening disparities in underserved populations.

The Future of Concurrent Automated Coronary Artery Calcium Scoring on Screening Low-Dose Computed Tomography.

Low-dose computed tomography (LDCT) has been extensively validated for lung cancer screening in selected patient populations. Additionally, the use of gated cardiac CT to assess coronary artery calcium (CAC) burden has been validated to determine a patient's risk for major cardiovascular adverse events. This is typically performed by calculating an Agatston score based on density and overall burden of calcified plaque within the coronary arteries. Patients that qualify for LDCT for lung cancer screening commonly share major risk factors for coronary artery disease and would frequently benefit from an additional gated cardiac CT for the assessment of CAC. Given the widespread use of LDCT for lung cancer screening, we evaluated current literature regarding the use of non-gated chest CT, specifically LDCT, for the detection and grading of coronary artery calcifications. Additionally, given the evolving and increasing use of artificial intelligence (AI) in the interpretation of radiologic studies, current literature for the use of AI in CAC assessment was reviewed. We reviewed primary scientific literature dating up to April 2020 using Pubmed and Google Scholar, with the search terms low dose CT, lung cancer screening, coronary artery calcium, EKG/cardiac gated CT, deep learning, machine learning, and AI. These publications were then independently evaluated by each member of our team. Overall, there was a consensus within these papers that LDCT for lung cancer screening plays a role in the evaluation of CAC. Most studies note the inherent problems with the evaluation of the density of coronary calcifications on LDCT to give an accurate numeric calcium or Agatston score. The current method of evaluating CAC on LDCT involves using a qualitative categorical system (none, mild, moderate, or severe). When performed by cardiac imaging experts, this method broadly correlates with traditional CAC score groups (0, 1 to 100, 101 to 400, and > 400). Furthermore, given the high sensitivity of a properly protocolled LDCT for coronary calcium, a negative study for CAC precludes the need for a dedicated gated CT assessment. However, qualitative methods are not as accurate or reproducible when performed by general radiologists. The implementation of AI in the LDCT screening process has the potential to give a quantifiable and reproducible numeric value to the calcium score, based on whole heart volume scoring of calcium. This more closely aligns with the Agatston score and serves as a better guide for treatment and risk assessment using current guidelines.We conclude that CAC should be assessed on all LDCT performed for lung cancer screening and that a qualitative categorical scoring system should be provided in the impression for each patient. Early studies involving AI for the assessment of CAC are promising, but more extensive studies are needed before a final recommendation for its use can be given. The implementation of an accurate, automated AI CAC assessment tool would improve radiologist compliance and ease of overall workflow. Ultimately, the potential end result would be improved turnaround time, better patient outcomes, and reduced healthcare costs by maximizing preventative care in this high-risk population.

Does low-dose computed tomography screening improve lung cancer-related outcomes?—a systematic review

: Screening with low-dose computed tomography (LDCT) can potentially decrease the mortality rate of lung cancer by detecting tumors at earlier stages. Although a number of guidelines exist on the implementation of screening and the management of screening-detected lesions, the field has progressed since those were written in terms of the clinical data now available and the greater range of surgical options now on offer to patients. This systematic review aims to provide an updated assessment of how LDCT screening may impact lung cancer-related outcomes in light of such recent data and surgical progress. A systematic literature search was conducted to identify articles focused on the use of LDCT to screen for primary non-small cell lung cancer in asymptomatic individuals. Of 2,880 articles identified, high quality papers reporting the results of 27 major studies were selected for in-depth analysis—including 17 observational studies (15 prospective and 2 retrospective), and 11 randomised-controlled trials. LDCT screening detected lung cancer in 0–8.2% of asymptomatic adults subject. These rates were demonstrated in most studies to be significantly higher than the lung cancer detection rate with no screening. Invasive procedures for benign lesions were performed in 0.07–1.9% of LDCT-screened subjects. Most LDCT screening-detected lung cancers presented in stage I, and 52–100% of patients with LDCT-detected lung cancer received surgery. Two large randomized-controlled trials showed that LDCT screening was associated with a 20.0% reduction in mortality when compared to chest X-ray (CXR) screening, and a 26% reduction in mortality when compared to no screening. LDCT screening is associated with: higher rates of lung cancer detection; diagnosis of lung cancer at an earlier stage; greater likelihood of surgical therapy being given; and lower mortality from lung cancer. The rate of ‘unnecessary’ interventions as a result of LDCT screening is low.

Impact of low-dose computed tomography screening on lung cancer mortality among asbestos-exposed workers.

We previously showed that low-dose computed tomography (LDCT) screening in asbestos-exposed workers is effective in detecting lung cancer (LC) at an early stage. Here, we evaluate whether LDCT screening could reduce mortality from LC in such a high-risk population. Within a cohort of 2433 asbestos-exposed men enrolled in an Occupational Health surveillance programme, we compared mortality between the participants in the ATOM002 study (LDCT-P, N = 926) and contemporary non-participants (LDCT-NP, N = 1507). We estimated standardized mortality ratios for the LDCT-P and LDCT-NP populations using regional and national rates (SMR_FVG and SMR_ITA, respectively). We compared survival for all causes, all neoplasms, LC and malignant neoplasm of pleura (MNP) between LDCT-P and LDCT-NP using Cox proportional hazard models adjusted for age, smoking history, asbestos exposure level and comorbidities. A reduction in mortality from LC was observed in the LDCT-P group compared with regional and national figures (SMR_FVG = 0.55, 95% confidence interval (CI) 0.24-1.09; SMR_ITA = 0.51, 95% CI 0.22-1.01); this was not the case for the LDCT-NP group (SMR_FVG = 2.07, 95% CI 1.53-2.73; SMR_ITA = 1.98, 95% CI 1.47-2.61). A strong reduction in LC mortality was observed for the LDCT-P compared with the LDCT-NP [hazard ratio (HR) = 0.41, 95% CI 0.17-0.96]. Mortality was also reduced for all causes (HR = 0.61, 95% CI 0.44-0.84), but not for all neoplasms (HR = 0.97, 95% CI 0.62-1.50) and MNP (HR = 0.86, 95% CI 0.31-2.41) within the LDCT-P population. In our cohort, participation in the LDCT screening study was associated with reduced mortality from LC. This finding supports the use of LDCT in surveillance programmes for asbestos-exposed workers.

Reflections on the Implementation of Low-dose Computed Tomography Screening in Individuals at High Risk of Lung Cancer in Spain

Lung cancer (LC) is a major public health issue. Despite recent advances in treatment, primary prevention and early diagnosis are key to reducing the incidence and mortality of this disease. A recent clinical trial demonstrated the efficacy of selective screening by low-dose computed tomography (LDCT) in reducing the risk of both lung cancer mortality and all-cause mortality in high-risk individuals.This article contains the reflections of an expert group on the use of LDCT for early diagnosis of LC in high-risk individuals, and how to evaluate its implementation in Spain. The expert group was set up by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM).

The Effect of Primary Care Physician Knowledge of Lung Cancer Screening Guidelines on Perceptions and Utilization of Low-Dose Computed Tomography

IntroductionLung cancer screening (LCS) with low-dose computed tomography (LDCT) is recommended by the U.S. Preventive Services Task Force (USPSTF) in high-risk patients, but a minority of eligible people are screened. It is not clear whether knowledge of USPSTF recommendations among primary care physicians (PCP) affects utilization of LDCT. MethodsA randomly selected sample of 1384 PCPs in Los Angeles County was surveyed between January and October 2015, using surveys sent by mail, fax, and e-mail. The response rate was 18% (n = 250). Training background, years in practice, practice type, and respondent demographics were collected. We analyzed results based on the response to a question on whether the USPSTF recommends the use of LDCT to screen high-risk individuals for lung cancer. ResultsA total of 117 (47%) PCPs responded that the USPSTF recommends LDCT for LCS. Of PCPs who were aware of USPSTF recommendations, 97% responded that CT was effective at reducing lung cancer mortality among individuals meeting eligibility criteria, compared with 90% who were unaware of guidelines (P = .02). A larger proportion of PCPs aware of guidelines ordered LDCT (71% vs. 38%, P < .001) and initiated a discussion on screening (86% vs. 62%, P < .001). Both groups of PCPs reported similar perceptions of barriers to screening, such as insurance coverage, risks of LCS, and cost to society. Practice size, training background, and years in practice did not affect knowledge of guidelines. DiscussionAwareness of USPSTF recommendations for LDCT is associated with increased utilization of LDCT for screening. Educational interventions for PCPs may improve adherence with LCS recommendations.

Reflexiones sobre la implementación del cribado mediante tomografía computarizada de baja dosis en personas con riesgo elevado de padecer cáncer de pulmón en España

Lung cancer (LC) is a major public health issue. Despite recent advances in treatment, primary prevention and early diagnosis are key to reducing the incidence and mortality of this disease. A recent clinical trial demonstrated the efficacy of selective screening by low-dose computed tomography (LDCT) in reducing the risk of both lung cancer mortality and all-cause mortality in high-risk individuals.This article contains the reflections of an expert group on the use of LDCT for early diagnosis of LC in high-risk individuals, and how to evaluate its implementation in Spain. The expert group was set up by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM).

P1.03-053 The Effect of Primary Care Physician Knowledge of Lung Cancer Screening Guidelines on Perceptions and Utilization of Low Dose CT

Lung cancer screening with low-dose computed tomography (LDCT) is recommended by the U.S. Preventive Services Task Force (USPSTF) in high-risk patients, but a minority of eligible people is screened. It is unknown whether knowledge of USPSTF recommendations among primary care physicians (PCP) impacts perceived benefits and utilization of LDCT. As we previously reported, a randomly selected sample of 1384 primary care physicians in Los Angeles County was surveyed between January and October 2015, using surveys sent by mail, fax, and email. The response rate was 18%. Training background, years in practice, practice type, and respondent demographics were collected. We analyzed results based on the response to a question on whether the USPSTF recommends the use of LDCT to screen high-risk individuals for lung cancer. One hundred seventeen (47%) PCPs responded that the USPSTF recommends LDCT for LCS. Of PCPs who were aware of USPSTF recommendations, 94% responded that CT was somewhat or very effective at reducing lung cancer mortality among individuals meeting eligibility criteria, compared with 79% who were unaware (p=0.013). 27% of those aware of the recommendations thought chest X-ray (CXR) was effective at reducing lung cancer mortality compared with 62% of unaware PCPs (p=0.001). A similar number of PCPs in each group ordered CXR for screening over the past 12 months, but a larger proportion of PCPs aware of guidelines ordered LDCT (69% vs 36%, p <0.001) and initiated a discussion on screening (84% vs 59%, p<0.001) over the past 12 month. 14% of PCPs aware of guidelines reported that benefits of LCS were not clear to them compared with 43% of those unaware of guidelines (p<0.001). Both groups of PCPs reported similar scores when questioned on other barriers to screening such as insurance coverage, risks of LCS, and cost to society. There were no differences between groups by practice size, training background, years in practice, or PCP demographics. Awareness of USPSTF recommendations for lung cancer screening is associated with the perception of benefit of LDCT and with increased utilization of LDCT for screening. Educational interventions for PCPs may improve adherence with LCS recommendations.

Lung cancer screening in high-risk subjects: early detection with LDCT and risk stratification using miRNA-based blood test

Lung cancer still remains a high mortality disease in the face of developments in diagnostic and therapeutic methods that occurred in the last 20 years. The analysis of the experiences from the first studies - in which chest X-ray (CXR) was adopted, associated or not with sputum cytology - has failed to show a reduction in lung cancer specific mortality. Subsequent screening studies that have introduced the use of low-dose computed tomography (LDCT) have revealed a large number of early-stage lung cancers, thus potentially curable; however, this has not allowed us to demonstrate a decrease in lung cancer-specific mortality. With the results of the American study National Lung ScreeningTrial (NLST), published in 2011, for the first time a lung cancer-specific mortality reduction by 20% thanks to the use of LDCT compared to RXT, was highlighted. However, a false discovery rate of 96.4% was also described with an overdiagnosis that can be up to 78.9% for bronchioalveolar lung cancer. Due to the high sensitivity of LDCT, able to identify a non-calcified pulmonary nodule in one subject on two, it becomes necessary to avail instruments to more accurately identify suspicious nodules. Until some time ago, the possible use of lung tumour markers was not viable in view of the poor organ specificity. The study and development was, then, pushed to organ- and tissue-specific markers such as microRNA (miRNA), noncoding RNA sequences involved in many processes and expression of oncogenic activity of the microenvironment. The use of biomarkers such as circulating miRNA implemented in LDCT screening has highlighted a reduction of 5 times for the rate of false positives, going from 19.4% to 3.7%, with a sensitivity of 87%, a specificity of 81%, and a negative predictive value of 99%. The need to appropriately use the available resources commensurate with the disease to treat will push more and more towards the implementation of LDCT biomarkers based screenings, stable and easily reproducible, as circulating miRNAs, obviating to problems such as false positives, unnecessary procedures of invasive surgery for benign lesions, and optimizing the cost benefit ratios.The development of new specific biomarkers appears to offer new promising prospects.

Clinical relevance of circulating microRNAs as lung cancer biomarkers

INVITED SPEAKER ABSTRACTS Clinical relevance of circulating microRNAs as lung cancer biomarkers Mattia Boeri, Gabriella Sozzi, Ugo Pastorino Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy Improvements in clinical management of lung cancer have been modest over the last 20 years and with almost 1.6 million deaths worldwide (19% of the total) it still has the highest mortality rate among cancers. So far no valid biomarker has proven to be useful in lung cancer clinical practice and in reducing mortality. Technical limitations, as well as genetic and biological tumor heterogeneity have likely limited the successful identification of tumorspecific markers. An interesting landmark to identify novel and more reliable biomarkers is searching for candidates by looking not only at the tumor itself but also at the interplay between the tumor and the host with the aim to identify changes related to the biological reactivity of the host to a developing cancer. MicroRNAs (miRNAs) are 19 to 25 nucleotide-long non-coding RNAs regulating gene expression by binding complementary sequences of target mRNAs. MicroRNAs have a role in cell-to cell communication and are actively released in the extracellular space included in vesicles or bounded to proteins protecting them from RNase activity. In this respect, circulating microRNAs represent ideal candidates since biomarkers could reflect both the early changes in the pulmonary environment or the cross-talk between the tumor and its surrounding microenvironment. MicroRNAs-based liquid biopsies are emerging as promising tools for individual risk stratification, for the diagnosis and prognosis of lung cancer and more recently as predictive biomarkers of response to therapy. In our Institution, a specific circulating microRNA signatures classifier (MSC) was generated and validated in plasma samples collected from volunteers enrolled in Low Dose Computed Tomography (LDCT) lung cancer screening trials, in order to set-up a minimally invasive test able to detect lung cancer in its early stages. LDCT is considered the gold standard for the early detection of lung cancer. Results of a USA randomized screening trial reported a significant increase in the number of lung cancer diagnoses, especially at lower stages, and a Journal of Thoracic Oncology Vol. 11 No. 2S: S2-S15 reduction of mortality up to 20%. On the other hand, two major issues emerged from screening studies: the high number of false positive cases identified by LDCT (over 95%) and the overdiagnosis issue (estimated over 18% in the NLST trial), leading to further examinations or unnecessary surgical procedures with remarkable increasing of costs and morbidities. The MSC stratifies patients in 3 levels of risk: high, intermediate and low. In large retrospective studies using plasma samples collected from more than 1000 volunteers enrolled in the INT/IEO and in the MILD screening trials, the MSC resulted in 87% sensitivity, 81% specificity and 99% negative predictive value. Moreover, the combined use of LDCT and the MSC test showed a 5-fold reduction in the number of false positive cases obtained with LDCT alone. Considering the 111 (3.3%) lung cancer cases detected during the first 5 years of these two screening trials, 84 had a plasma sample available to perform the MSC test. In this cohort the MSC was able to predict the disease occurrence two years before LDCT detection and the 5-year survival was respectively 88.9% for low risk MSC, 79.5% for intermediate risk MSC and 40.1% for high risk MSC (p1⁄40.001). Another possible use of liquid biopsy could be the monitoring of the disease status after treatment or surgical resection. The MSC test was thus employed to analyze 100 longitudinally-collected plasma samples obtained from 31 alive patients (28 disease-free and 3 relapsing) after surgical resection of primary lung tumors. Considering the 25 disease-free patients positive to the MSC test at the time of diagnosis, a reduction of MSC risk profile was observed in 19 (76%) post-surgery plasma samples. Whereas in the 3 relapsing patients an increase of the MSC risk level was observed at the time of detection of second primary tumor or metastatic progression. So far the MSC test showed very promising results in screening settings, being able to improve individual risk assessment and the performance of LDCT. Further analysis will provide information about the sensitivity of the MSC in clinically detected lung cancer. The MSC risk levels are also being evaluated according to other risk factors such as smoking habits (measured as Pack Year), the inflammation levels (measured as C-reactive protein) or the forced expiratory volume (FEV-1). Finally, by targeted NGS we are profiling the mutational load of screening detected tumors in order to analyze association with the MSC risk profile.

Lung Cancer Screening: Computed Tomography Radiation and Protocols.

Recent studies have supported the use of low-dose computed tomography (LDCT) of the chest as a screening tool for lung cancer. Several professional organizations have now included LDCT screening in high-risk populations in their guidelines. The United States Preventive Services Task Force has added LDCT to its lung cancer-screening guidelines as of December 2013. Recently, the Centers for Medicare and Medicaid Services acknowledged that the evidence for LDCT lung cancer screening is adequate, provided that eligibility criteria are met. As widespread use of LDCT is anticipated, the radiation dose associated with LDCT needs to be optimized. The American College of Radiology-Society of Thoracic Radiology collaboration and the National Comprehensive Cancer Care Network recently provided some guidelines for LDCT utilization for lung cancer screening. There are several scanning and image reconstruction techniques that can be used for reducing radiation dose in LDCT lung cancer screening. This review article presents protocols and guidelines for use of LDCT in lung cancer screening and describes our early experience in implementing LDCT at our institution.

Abstract 871: Clinical utility of a plasma microRNA biomarker within lung cancer screening

Abstract Recent screening trials indicate that low-dose computed tomography (LDCT) reduces lung-cancer mortality in high risk subjects. However, high false positive rates, costs and potential harms highlight the need for complementary biomarkers. MicroRNAs (miRNAs) are tissue and disease specific molecules, actively released by cells in the circulatory system, which are associated with protein complexes and/or packaged in exosomes and microvesicles. Circulating miRNAs are rather stable and easily detectable in body fluids suggesting the possibility of using miRNAs as a new promising class of biomarkers. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) of a non-invasive plasma miRNA signature classifier (MSC) to identify lung cancer occurrence and mortality was retrospectively evaluated in samples prospectively collected from smokers within the randomized Multicentre Italian Lung Detection (MILD) trial. Plasma samples from 939 subjects including 69 lung cancer patients and 870 disease-free individuals were analyzed using a Real-Time quantitative PCR (qRT-PCR) based assay for MSC. Combined sensitivity and specificity of plasma MSC and LDCT were assessed in a blinded validation study. MSC correctly identified patients with lung cancer at 87% sensitivity, 81% specificity, and 99% NPV, and 18 of 19 lung cancer deaths at 95% sensitivity 81% specificity, and 99.86% NPV. MSC identified 43 of 49 (88%) LDCT-detected cancers, 8 of 9 (89%) interval cancers in the LDCT arm, and 9 of 11 (82%) cancers in the observational arm. Diagnostic performance of MSC was confirmed by time dependency analysis. MSC fell to negative after lung cancer resection in 16 of 22 evaluable subjects. In lung cancer patients, there was a trend in mortality across levels of MSC (p=0.0336) and survival rate significantly differed according to MSC in all subjects (X21=49.53, p&amp;lt;0.0001). Combination of MSC and LDCT resulted in a 5-fold reduction of LDCT false positive rate. This large validation study highlights the clinical diagnostic and prognostic value of plasma MSC for lung cancer screening in high-risk populations. The combined use of LDCT and MSC could reduce the false positive rate of LDCT improving the efficacy of lung cancer screening. Citation Format: Mattia Boeri, Carla Verri, Gabriella Sozzi, Luca Roz, Davide Conte, Paola Suatoni, Alfonso Marchiano, Carlo La Vecchia, Marta Rossi, Francesca Bravi, Eva Negri, Nicola Sverzellati, Ugo Pastorino. Clinical utility of a plasma microRNA biomarker within lung cancer screening. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 871. doi:10.1158/1538-7445.AM2014-871

Low-dose CT for quantitative analysis in acute respiratory distress syndrome

IntroductionThe clinical use of serial quantitative computed tomography (CT) to characterize lung disease and guide the optimization of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) is limited by the risk of cumulative radiation exposure and by the difficulties and risks related to transferring patients to the CT room. We evaluated the effects of tube current-time product (mAs) variations on quantitative results in healthy lungs and in experimental ARDS in order to support the use of low-dose CT for quantitative analysis.MethodsIn 14 sheep chest CT was performed at baseline and after the induction of ARDS via intravenous oleic acid injection. For each CT session, two consecutive scans were obtained applying two different mAs: 60 mAs was paired with 140, 15 or 7.5 mAs. All other CT parameters were kept unaltered (tube voltage 120 kVp, collimation 32 × 0.5 mm, pitch 0.85, matrix 512 × 512, pixel size 0.625 × 0.625 mm). Quantitative results obtained at different mAs were compared via Bland-Altman analysis.ResultsGood agreement was observed between 60 mAs and 140 mAs and between 60 mAs and 15 mAs (all biases less than 1%). A further reduction of mAs to 7.5 mAs caused an increase in the bias of poorly aerated and nonaerated tissue (-2.9% and 2.4%, respectively) and determined a significant widening of the limits of agreement for the same compartments (-10.5% to 4.8% for poorly aerated tissue and -5.9% to 10.8% for nonaerated tissue). Estimated mean effective dose at 140, 60, 15 and 7.5 mAs corresponded to 17.8, 7.4, 2.0 and 0.9 mSv, respectively. Image noise of scans performed at 140, 60, 15 and 7.5 mAs corresponded to 10, 16, 38 and 74 Hounsfield units, respectively.ConclusionsA reduction of effective dose up to 70% has been achieved with minimal effects on lung quantitative results. Low-dose computed tomography provides accurate quantitative results and could be used to characterize lung compartment distribution and possibly monitor time-course of ARDS with a lower risk of exposure to ionizing radiation. A further radiation dose reduction is associated with lower accuracy in quantitative results.

Is computed tomography follow-up of patients after lobectomy for non-small cell lung cancer of benefit in terms of survival?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether following up patients after lobectomy for non-small cell lung cancer (NSCLC) with computed tomography (CT) scanning is of benefit in terms of survival. Altogether, 448 papers were found using the reported search, of which five represented the best evidence to answer the clinical question and three provided supporting evidence. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. There is no general consensus in the literature. From the limited number of papers that address the effect of CT follow-up on survival following surgery for NSCLC, three showed that CT scanning may improve the survival of patients by detecting local and distant recurrences at an earlier stage when the patient is asymptomatic. One paper showed that detection by the use of low-dose CT or simultaneous chest CT plus positron emission tomography-CT led to a longer duration of survival compared with detection by clinical suspicion (2.1 ± 0.3 vs 3.6 ± 0.2 years, p = 0.002). However, two papers broadly showed that follow-up with CT does not improve survival outcomes regardless of the site of recurrence. One such study showed that there was no clinically significant difference in survival whether patients were followed up using a strict CT protocol compared with a symptom-based follow-up (median survival after recurrence: strict 7.9 months, symptom-based 6.6 months, p = 0.219). The remaining papers supported the use of CT as a screening tool for recurrence but did not comment directly on survival. Owing to the limited and contradictory evidence, there is a need for an randomized controlled trial to assess the survival outcomes of patients followed up with a CT screening protocol vs a symptom-based follow-up.