BackgroundITALUNG is contributing to the European evaluation of low-dose CT (LDCT) screening for lung cancer (LC).MethodsEligible subjects aged 55–69 years, smokers or ex-smokers (at least 20 ...pack-years in the last 10 years), were randomised to receive an annual invitation for LDCT screening for 4 years (active group) or to usual care (control group). All participants were followed up for vital status and cause of death (at the end of 2014) and LC incidence (at the end of 2013). Pathological and clinical information was collected from the Tuscan Cancer Registry data.Results1613 subjects were randomly assigned to the active group and 1593 to the control group. At the end of the follow-up period 67 LC cases were diagnosed in the active group and 71 in the control group (rate ratio (RR)=0.93; 95% CI 0.67 to 1.30). A greater proportion of stage I LC was observed in the active group (36% vs 11%, p<0.001). Non-significant reductions of 17% (RR=0.83; 95% CI 0.67 to 1.03) for overall mortality and 30% (RR=0.70; 95% CI 0.47 to 1.03) for LC-specific mortality were estimated.ConclusionsDespite the lack of statistical significance, the ITALUNG trial outcomes suggest that LDCT screening could reduce LC and overall mortality. Moreover, the comparison of the number of LC cases diagnosed in the two groups does not show overdiagnosis after an adequate follow-up period. A pooled analysis of all European screening trials is advocated to assess the benefit-to-harm ratio of LDCT screening and its implementation in public health settings.Trial registration numberResults, NCT02777996.
Summary Background Results of randomized clinical trials (RCTs) are needed to assess the efficacy of lung cancer screening with low-dose chest computed tomography (CT) in reducing lung cancer ...mortality. We report design and results of enrolment and baseline screening test in the ITALUNG trial, a RCT. Methods Invitation letters were sent to subjects of 55–69 years of age clients of 269 general practitioners. Smokers or former smokers of at least 20 pack/years were eligible and after written consent were randomized in an active arm undergoing a low-dose CT annually for 4 years and in a control arm receiving no screening. Management of positive screening test was carried out using follow-up low-dose CT, fluorodeoxyglucose positron emission tomography, fine needle aspiration cytology and fiber optic bronchoscopy. Results A sample of 3206 eligible subjects was achieved by sending 71,232 letters (enrolment efficacy = 4.5%). Subjects in control ( n = 1593) and active ( n = 1613) arm were balanced for age, gender and smoking history. Two-hundred and seven (12.8%) subjects did not undergo CT after randomization. The baseline screening test was positive in 426 (30.3%) of 1406 subjects. Twenty-one lung cancers (prevalence = 1.5%) were found in 20 subjects: 18 non-small cell lung cancer (NSCLC), 2 small cell lung cancer (SCLC) and a case of typical carcinoid. Ten NSCLC (47.6%) were in Stage I. Sixteen fine needle aspirations were performed in 15 lung cancers, with a positive result in 12 (75%) cases. One biopsy only (6.3%) was performed on a benign lesion. Seventeen lung cancers (81%) were treated with surgical resection in 16 subjects. One subject underwent surgery for a benign lesion (5.5% of all surgical resections). Conclusions Recruitment by mail of high risk subjects for a lung cancer screening RCT is feasible but not efficient. Results of the baseline screening test in the active arm of the ITALUNG trial are substantially in line with those of RCT and observational studies.
Recruitment and nodule management are critical issues of lung cancer screening with low-dose computed tomography (LDCT). We report subjects’ compliance and results of LDCT screening and management ...protocol in the active arm of the ITALUNG trial.
Three thousand two hundred six smokers or former smokers invited by mail were randomized to receive four annual LDCT (n = 1613) or usual care (n = 1593). Management protocol included follow-up LDCT, 2-18Ffluoro-2-deoxy-D glucose positron emission tomography (FDG-PET), and CT-guided fine-needle aspiration biopsy (FNAB).
One thousand four hundred six subjects (87%) underwent baseline LDCT, and 1263 (79%) completed four screening rounds. LDCT was positive in 30.3% of the subjects at baseline and 15.8% subsequently. Twenty-one lung tumors in 20 subjects (1.5% detection) were found at baseline, and 20 lung tumors in 18 subjects (0.5% detection) in subsequent screening rounds. Ten of 18 prevalent (55%) and 13 of 17 incident (76%) non–small-cell cancers were in stage I. Interval growth enabled diagnosis of lung cancer in 16 subjects (42%), but at least one follow-up LDCT was obtained in 741 subjects (52.7%) over the screening period. FDG-PET obtained in 6.5% of subjects had 84% sensitivity and 90% specificity for malignant lesions. FNAB obtained in 2.4% of subjects showed 90% sensitivity and 88% specificity. Positivity of both FDG-PET and FNAB invariably predicted malignancy. Surgery for benign lesions was performed on four subjects (10% of procedures) but followed protocol violations on three subjects.
High-risk subjects recruited by mail who entered LDCT screening showed a high and stable compliance. Efficacy of screening is, however, weakened by low detection rate and specificity. Adhesion to management protocol might lessen surgery for benign lesions.
Asymptomatic high‐risk subjects, randomized in the intervention arm of the ITALUNG trial (1,406 screened for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1,356), in which samples ...of blood and sputum were analyzed for plasma DNA quantification (cut off 5 ng/ml), loss of heterozygosity and microsatellite instability. The ITALUNG biomarker panel (IBP) was considered positive if at least one of the two biomarkers included in the panel was positive. Subjects with and without lung cancer diagnosis at the end of the screening cycle with LDCT (n = 517) were evaluated. Out of 18 baseline screen detected lung cancer cases, 17 were IBP positive (94%). Repeat screen‐detected lung cancer cases were 18 and 12 of them positive at baseline IBP test (66%). Interval cancer cases (2‐years) and biomarker tests after a suspect Non Calcific Nodule follow‐up were investigated. The single test versus multimodal screening measures of accuracy were compared in a simulation within the screened ITALUNG intervention arm, considering screen‐detected and interval cancer cases. Sensitivity was 90% at baseline screening. Specificity was 71 and 61% for LDCT and IBP as baseline single test, and improved at 89% with multimodal, combined screening. The positive predictive value was 4.3% for LDCT at baseline and 10.6% for multimodal screening. Multimodal screening could improve the screening efficiency at baseline and strategies for future implementation are discussed. If IBP was used as primary screening test, the LDCT burden might decrease of about 60%.
What's new?
Low‐dose computed tomography (LDCT) for lung cancer screening is associated with a high frequency of detection of pulmonary nodules of uncertain clinical significance. Here, to better identify high‐risk individuals, LDCT was combined with biomarker detection as part of ITALUNG, an LDCT lung cancer screening trial in Italy. The ITALUNG Biomarker Panel (IBP), consisting of plasma DNA quantification, loss of heterozygosity, and microsatellite instability, showed high sensitivity for lung cancer detection at baseline screening. Specificity increased to 89% with the multimodal approach, suggesting that combined use of LDCT and IBP can significantly improve the effectiveness of lung cancer screening.
Track finding efficiency in BABAR Allmendinger, T.; Bhuyan, B.; Brown, D.N. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2013, Volume:
704
Journal Article
Peer reviewed
Open access
We describe several studies to measure the charged track reconstruction efficiency and asymmetry of the BABAR detector. The first two studies measure the tracking efficiency of a charged particle ...using τ and initial state radiation decays. The third uses the τ decays to study the asymmetry in tracking, the fourth measures the tracking efficiency for low momentum tracks, and the last measures the reconstruction efficiency of KS0 particles. The first section also examines the stability of the measurements vs. BABAR running periods.
Using data from the FOCUS (E831) experiment, we have searched for T violation in charm meson decays using the four-body decay channels D0→K−K+π−π+, D+→KS0K+π−π+, and Ds+→KS0K+π−π+. The T violation ...asymmetry is obtained using triple-product correlations and assuming the validity of the CPT theorem. We find the asymmetry values to be ATviol(D0)=0.010±0.057(stat.)±0.037(syst.), ATviol(D+)=0.023±0.062(stat.)±0.022(syst.), and ATviol(Ds+)=−0.036±0.067(stat.)±0.023(syst.). Each measurement is consistent with no T violation. New measurements of the CP asymmetries for some of these decay modes are also presented.
Abstract The aim of this study was to evaluate the diagnostic value of a grid of molecular genetic markers detectable in sputum and plasma samples of individuals enrolled in a lung cancer screening ...program with low-dose CT. Subjects enrolled in the baseline screening round of the ITALUNG (randomised) screening trial were invited to provide biological specimens for molecular analysis (1356 subjects out of 1406). We included 98 subjects in this analysis. There was a highly statistically significant difference between proportion of subjects with a negative baseline CT screening test who were positive to allelic imbalance, and those with a non-calcified nodule (NCN greater than or equal to 5 mm), the reason of recall for all suspects at CT Scan ( χ2 : 22.9; P < 0.0001). Allelic imbalance showed good performance for screening of NCN ≥5 mm. In subjects recalled for NCN ≥5 mm, LOH, K-ras mutations and high levels of free plasma DNA (>5 ng/ml plasma) might be important to support clinical decision making for further follow-up and repeated screening. This study, embedded in an early diagnosis randomised trial, suggests that a multi-screening approach integrating imaging technique and a biomolecular marker panel is worth of further investigation.
We review genetic programming principles, their application to FOCUS data samples, and use the method to study the doubly Cabibbo suppressed decay
D
+
→
K
+
π
+
π
-
relative to its Cabibbo favored ...counterpart,
D
+
→
K
-
π
+
π
+
. We find that this technique is able to improve upon more traditional analysis methods. To our knowledge, this is the first application of the genetic programming technique to High Energy Physics data.
Track finding efficiency in B A B AR Allmendinger, T.; Bhuyan, B.; Brown, D.N. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2013, Volume:
704
Journal Article
Track finding efficiency in Allmendinger, T.; Bhuyan, B.; Brown, D. N. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2012, Volume:
704, Issue:
C
Journal Article
Peer reviewed
Open access
We describe several studies to measure the charged track reconstruction efficiency and asymmetry of the BaBar detector. The first two studies measure the tracking efficiency of a charged particle ...using τ and initial state radiation decays. The third uses the τ decays to study the asymmetry in tracking, the fourth measures the tracking efficiency for low momentum tracks, and the last measures the reconstruction efficiency of K$0\atop{S}$ particles. The first section also examines the stability of the measurements vs. BaBar running periods.
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