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PURPOSE: To investigate the early radiological features and survival of Large Cell Carcinoma (LCC) cases diagnosed in low-dose computed tomography (LDCT) screening trials. METHODS: Two radiologists jointly reviewed the radiological features of screen-detected LCCs observed in NLST, ITALUNG, and LUSI trials between 2002 and 2016, comprising a total of 29,744 subjects who underwent 3-5 annual screening LDCT examinations. Survival or causes of death were established according to the mortality registries extending more than 12 years since randomization. RESULTS: LCC was diagnosed in 30 (4 %) of 750 subjects with screen-detected lung cancer (LC), including 15 prevalent and 15 incident cases. Three additional LCCs occurred as interval cancers during the screening period. LDCT images were available for 29 cases of screen-detected LCCs, and 28 showed a single, peripheral, and well-defined solid nodule or mass with regularly smooth (39 %), lobulated (43 %), or spiculated (18 %) margins. One case presented as hilar mass. In 9 incident LCCs, smaller solid nodules were identified in prior LDCT examinations, allowing us to calculate a mean Volume Doubling Time (VDT) of 98.7 ± 47.8 days. The overall five-year survival rate was 50 %, with a significant (p = 0.0001) difference between stages I-II (75 % alive) and stages III-IV (10 % alive). CONCLUSIONS: LCC is a fast-growing neoplasm that can escape detection by annual LDCT screening. LCC typically presents as a single solid peripheral nodule or mass, often with lobulated margins, and exhibits a short VDT. The 5-year survival reflects the stage at diagnosis.
ABSTRACT
The role of total plasma cell-free DNA (cfDNA) in lung cancer (LC) screening with low-dose computed tomography (LDCT) is uncertain. We hypothesized that cfDNA could support differentiation between malignant and benign nodules observed in LDCT. The baseline cfDNA was measured in 137 subjects of the ITALUNG trial, including 29 subjects with screen-detected LC (17 prevalent and 12 incident) and 108 subjects with benign nodules. The predictive capability of baseline cfDNA to differentiate malignant and benign nodules was compared to that of Lung-RADS classification and Brock score at initial LDCT (iLDCT). Subjects with prevalent LC showed both well-discriminating radiological characteristics of the malignant nodule (16 of 17 were classified as Lung-RADS 4) and markedly increased cfDNA (mean 18.8 ng/mL). The mean diameters and Brock scores of malignant nodules at iLDCT in subjects who were diagnosed with incident LC were not different from those of benign nodules. However, 75% (9/12) of subjects with incident LC showed a baseline cfDNA ≥ 3.15 ng/mL, compared to 34% (37/108) of subjects with benign nodules (p = 0.006). Moreover, baseline cfDNA was correlated (p = 0.001) with tumor growth, measured with volume doubling time. In conclusion, increased baseline cfDNA may help to differentiate subjects with malignant and benign nodules at LDCT.
ABSTRACT
The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer-aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover, ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as lung cancer associated with cystic airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs. biennial pace of LDCT, choice between opportunistic or population-based recruitment. and between uni or multi-centre screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema. and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention. and prospective validation of the biomarkers.
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OBJECTIVES: Cardiovascular disease (CVD), lung cancer (LC), and respiratory diseases are main causes of death in smokers and former smokers undergoing low-dose computed tomography (LDCT) for LC screening. We assessed whether quantification of pulmonary emphysematous changes at baseline LDCT has a predictive value concerning long-term mortality. METHODS: In this longitudinal study, we assessed pulmonary emphysematous changes with densitometry (volume corrected relative area below - 950 Hounsfield units) and coronary artery calcifications (CAC) with a 0-3 visual scale in baseline LDCT of 524 participants in the ITALUNG trial and analyzed their association with mortality after 13.6 years of follow-up using conventional statistics and a machine learning approach. RESULTS: Pulmonary emphysematous changes were present in 32.3% of subjects and were mild (6% ≤ RA950 ≤ 9%) in 14.9% and moderate-severe (RA950 > 9%) in 17.4%. CAC were present in 67% of subjects (mild in 34.7%, moderate-severe in 32.2%). In the follow-up, 81 (15.4%) subjects died (20 of LC, 28 of other cancers, 15 of CVD, 4 of respiratory disease, and 14 of other conditions). After adjusting for age, sex, smoking history, and CAC, moderate-severe emphysema was significantly associated with overall (OR 2.22; 95CI 1.34-3.70) and CVD (OR 3.66; 95CI 1.21-11.04) mortality. Machine learning showed that RA950 was the best single feature predictive of overall and CVD mortality. CONCLUSIONS: Moderate-severe pulmonary emphysematous changes are an independent predictor of long-term overall and CVD mortality in subjects participating in LC screening and should be incorporated in the post-test calculation of the individual mortality risk profile. KEY POINTS: ⢠Densitometry allows quantification of pulmonary emphysematous changes in low-dose CT examinations for lung cancer screening. ⢠Emphysematous lung density changes are an independent predictor of long-term overall and cardio-vascular disease mortality in smokers and former smokers undergoing screening. ⢠Emphysematous changes quantification should be included in the post-test calculation of the individual mortality risk profile.
Subject(s)
Cardiovascular Diseases , Coronary Artery Disease , Emphysema , Lung Neoplasms , Pulmonary Emphysema , Humans , Pulmonary Emphysema/diagnostic imaging , Smokers , Longitudinal Studies , Early Detection of Cancer , Lung Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Coronary Artery Disease/diagnostic imagingABSTRACT
Annual screening of lung cancer (LC) with chest low-dose computed tomography (CT) and screening of colorectal cancer (CRC) with CT colonography every 5 years are recommended by the United States Prevention Service Task Force. We review epidemiological and pathological data on LC and CRC, and the features of screening chest low-dose CT and CT colonography comprising execution, reading, radiation exposure and harm, and the cost effectiveness of the two CT screening interventions. The possibility of combining chest low-dose CT and CT colonography examinations for double LC and CRC screening in a single CT appointment is then addressed. We demonstrate how this approach appears feasible and is already reasonable as an opportunistic screening intervention in 50-75-year-old subjects with smoking history and average CRC risk. In addition to the crucial role Computer Assisted Diagnosis systems play in decreasing the test reading times and the need to educate radiologists in screening chest LDCT and CT colonography, in view of a single CT appointment for double screening, the following uncertainties need to be solved: (1) the schedule of the screening CT; (2) the effectiveness of iterative reconstruction and deep learning algorithms affording an ultra-low-dose CT acquisition technique and (3) management of incidental findings. Resolving these issues will imply new cost-effectiveness analyses for LC screening with chest low dose CT and for CRC screening with CT colonography and, especially, for the double LC and CRC screening with a single-appointment CT.
ABSTRACT
Smoking is the main risk factor for lung cancer (LC), which is the leading cause of cancer-related death worldwide. Independent randomized controlled trials, governmental and inter-governmental task forces, and meta-analyses established that LC screening (LCS) with chest low dose computed tomography (LDCT) decreases the mortality of LC in smokers and former smokers, compared to no-screening, especially in women. Accordingly, several Italian initiatives are offering LCS by LDCT and smoking cessation to about 10,000 high-risk subjects, supported by Private or Public Health Institutions, envisaging a possible population-based screening program. Because LDCT is the backbone of LCS, Italian radiologists with LCS expertise are presenting this position paper that encompasses recommendations for LDCT scan protocol and its reading. Moreover, fundamentals for classification of lung nodules and other findings at LDCT test are detailed along with international guidelines, from the European Society of Thoracic Imaging, the British Thoracic Society, and the American College of Radiology, for their reporting and management in LCS. The Italian College of Thoracic Radiologists produced this document to provide the basics for radiologists who plan to set up or to be involved in LCS, thus fostering homogenous evidence-based approach to the LDCT test over the Italian territory and warrant comparison and analyses throughout National and International practices.
Subject(s)
Lung Neoplasms , Radiology , Early Detection of Cancer/methods , Female , Humans , Lung Neoplasms/diagnostic imaging , Mass Screening , Radiography, Thoracic , Tomography, X-Ray Computed/methodsABSTRACT
PURPOSE: Coronary artery calcifications (CAC) are very strong indicators for increased cardio-vascular (CV) risk and can be evaluated also in low-dose computed tomography (LDCT) for lung cancer screening. We assessed whether a simple and fast CAC visual score is associated with CV mortality. METHODS: CAC were retrospectively assessed by two observers using a 4-score (absent, mild, moderate and severe) scale in baseline LDCT obtained in 1364 participants to the ITALUNG trial who had 55-69 years of age and a smoking history ≥20 pack-years. Correlations with CV risk factors at baseline and with CV mortality after 11 years of follow-up were investigated. RESULTS: CAC were absent in 470 (34.5%), mild in 433 (31.7%), moderate in 357 (26.2%) and severe in 104 (7.6%) subjects. CAC severity correlated (≤0.001) with age, male sex, pack-years, history of arterial hypertension or diabetes, obesity and treated hypercholesterolemia. Twenty-one CV deaths occurred. Moderate or severe CAC were significantly associated with higher CV mortality after adjustment for all other known risk factors (ARR = 2.72; 95 %CI:1.04-7.11). Notably, also in subjects with none or one only additional CV risk factor, the presence of moderate-severe CAC allowed to identify a subgroup of subjects with higher CV death risk (RR = 3.66; CI95%:1.06-12.6). CONCLUSIONS: Moderate or severe CAC visually assessed in LDCT examinations for lung cancer screening are independently associated with CV mortality.
Subject(s)
Calcinosis , Coronary Artery Disease , Lung Neoplasms , Vascular Calcification , Coronary Artery Disease/diagnostic imaging , Coronary Vessels , Early Detection of Cancer , Humans , Lung Neoplasms/diagnostic imaging , Male , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed , Vascular Calcification/diagnostic imagingABSTRACT
OBJECTIVES: Overdiagnosis in low-dose computed tomography randomized screening trials varies from 0 to 67%. The National Lung Screening Trial (extended follow-up) and ITALUNG (Italian Lung Cancer Screening Trial) have reported cumulative incidence estimates at long-term follow-up showing low or no overdiagnosis. The Danish Lung Cancer Screening Trial attributed the high overdiagnosis estimate to a likely selection for risk of the active arm. Here, we applied a method already used in benefit and overdiagnosis assessments to compute the long-term survival rates in the ITALUNG arms in order to confirm incidence-excess method assessment. METHODS: Subjects in the active arm were invited for four screening rounds, while controls were in usual care. Follow-up was extended to 11.3 years. Kaplan-Meyer 5- and 10-year survivals of "resected and early" (stage I or II and resected) and "unresected or late" (stage III or IV or not resected or unclassified) lung cancer cases were compared between arms. RESULTS: The updated ITALUNG control arm cumulative incidence rate was lower than in the active arm, but this was not statistically significant (RR: 0.89; 95% CI: 0.67-1.18). A compensatory drop of late cases was observed after baseline screening. The proportion of "resected and early" cases was 38% and 19%, in the active and control arms, respectively. The 10-year survival rates were 64% and 60% in the active and control arms, respectively (p = 0.689). The five-year survival rates for "unresected or late" cases were 10% and 7% in the active and control arms, respectively (p = 0.679). CONCLUSIONS: This long-term survival analysis, by prognostic categories, concluded against the long-term risk of overdiagnosis and contributed to revealing how screening works.
Subject(s)
Early Detection of Cancer , Lung Neoplasms/diagnosis , Medical Overuse , Aged , Early Detection of Cancer/methods , Female , Humans , Incidence , Italy/epidemiology , Lung/diagnostic imaging , Lung/surgery , Lung Neoplasms/epidemiology , Lung Neoplasms/mortality , Male , Middle Aged , Prognosis , Randomized Controlled Trials as Topic , Survival Analysis , Survival Rate , Tomography, X-Ray Computed/methodsABSTRACT
BACKGROUND: Changes in smoking habits and predictors of smoking cessation were examined in the randomized ITALUNG lung cancer screening trial. METHODS: In three centers, eligible smokers or ex-smokers (55-69 years, ≥20 pack-years in the last 10 years) were randomized to receive annual invitation for low-dose computed tomography for 4 years or usual care. At invitation, subjects received written information for a free smoking cessation program. Quitting outcome was assessed at year 4. RESULTS: Among participants who completed baseline assessments and year 4 screening, higher quitting (20.8% vs. 16.7%, p = .029) and lower relapse (6.41% vs. 7.56%, p = .50) rates were observed in the active screening group as compared to the usual-care control group. Corresponding figures in the intention-to-treat analysis were as follows: 16.04% versus 14.64% (p = .059) and 4.88% versus 6.43% (p = .26). Quitting smoking was significantly associated to male gender, lower pack-years, and having pulmonary nodules at baseline. Center-specific analyses showed a threefold statistically significant higher probability to quit associated with participating in the smoking cessation program. A subsample of smokers of the scan group from one center showed higher quitting rates over 12-month follow-up as compared to matched controls from the general population who underwent the same smoking cessation program. CONCLUSIONS: Consistently with previous reports, in the ITALUNG trial, screened subjects showed significantly higher quit rates than controls, and higher quit rates were associated with both the presence of pulmonary nodules and participating in a smoking cessation program. Maximal effect on quitting outcome was observed with the participation in the smoking cessation program. IMPLICATIONS: Participating in lung cancer screening promotes smoking cessation. An effective "teachable moment" may be achieved when the smoking cessation intervention is structured as integral part of the screening clinical visits and conducted by a dedicated team of health care professionals. Standardized guidelines for smoking cessation interventions in lung cancer screening are needed.
Subject(s)
Cigarette Smoking/adverse effects , Early Detection of Cancer/psychology , Lung Neoplasms/diagnosis , Patient Education as Topic/methods , Smokers/psychology , Smoking Cessation/psychology , Aged , Female , Humans , Italy/epidemiology , Lung Neoplasms/epidemiology , Lung Neoplasms/prevention & control , Male , Middle Aged , Motivation , Smoking Cessation/statistics & numerical data , Tomography, X-Ray ComputedABSTRACT
OBJECTIVES: In the ITALUNG lung cancer screening trial after 9.3 years of follow-up we observed an unexpected significant decrease of cardiovascular (CV) mortality in subjects invited for low-dose CT (LDCT) screening as compared to controls undergoing usual care. Herein we extended the mortality follow-up and analyzed the potential factors underlying such a decrease. MATERIALS AND METHODS: The following factors were assessed in screenes and controls: burden of CV disease at baseline, changes in smoking habits, use of CV drugs and frequency of planned vascular procedures after randomisation. Moreover, in the screenes we evaluated inclusion of presence of coronary artery calcification (CAC) in the LDCT report form that was transmitted to the participant and his/her General Practitioner. RESULTS: The 2-years extension of follow-up confirmed a significant decrease of CV mortality in the subjects of the active group compared to control subjects (15.6 vs 34.0 per 10,000; pâ¯=â¯0.001) that was not observed in the drops-out of the active group. None of the explaining factors we considered significantly differed between active and control group. However, the subjects of the active group with reported CAC experienced a not significantly lower CV mortality and showed a significantly higher use of CV drugs and frequency of planned vascular procedures than the control group. CONCLUSIONS: LDCT screening for lung cancer offers the opportunity for detection of CAC that is an important CV risk factor. Although the underlying mechanisms are not clear, our results suggest that the inclusion of information about CAC presence in the LDCT report may represent a candidate factor to explain the decreased CV mortality observed in screened subjects of the ITALUNG trial, possibly resulting in intervention for patient care to prevent CV deaths. Further studies investigating whether prospective reporting and rating of CAC have independent impact on such interventions and CV mortality are worthy.
Subject(s)
Coronary Artery Disease/mortality , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Vascular Calcification/mortality , Aged , Case-Control Studies , Coronary Artery Disease/etiology , Coronary Artery Disease/prevention & control , Databases, Factual , Early Detection of Cancer/statistics & numerical data , Female , Follow-Up Studies , Humans , Lung Neoplasms/complications , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Randomized Controlled Trials as Topic , Retrospective Studies , Risk Factors , Survival Rate , Tomography, X-Ray Computed/methods , Vascular Calcification/etiology , Vascular Calcification/prevention & controlABSTRACT
Occurrence of multiple primary lung cancers (MPLC) in individuals undergoing low-dose computed tomography (LDCT) screening has not been thoroughly addressed. We investigated MPLC in subjects recruited in the ITALUNG randomized clinical trial. Cases of cytologically/histologically proven MPLC detected at screening LDCT or follow-up CT were selected and pathologically re-evaluated according to the WHO 2015 classification. Overall 16 MPLC were diagnosed at screening LDCT (n=14, all present at baseline) or follow-up CT (n=2) in six subjects (4 in one subject, 3 in two and 2 in three subjects), representing 0.43% of the 1,406 screenees and 15.8% of the 38 subjects with at least one screen-detected primary lung cancer. MPLC included 9 adenocarcinomas in three subjects and a combination of 7 different tumour histotypes in three subjects. MPLC, mostly adenocarcinomas, are not uncommon in smokers and ex-smokers with at least one LDCT screen detected primary lung cancer.
ABSTRACT
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%.
Subject(s)
Biomarkers, Tumor/blood , Early Detection of Cancer , Lung Neoplasms/blood , Lung Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Aged , DNA, Neoplasm/blood , Female , Humans , Italy , Loss of Heterozygosity/genetics , Lung/diagnostic imaging , Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Mass Screening , Microsatellite Instability , Middle Aged , Multimodal Imaging , Smoking , Sputum/metabolismABSTRACT
BACKGROUND: ITALUNG is contributing to the European evaluation of low-dose CT (LDCT) screening for lung cancer (LC). METHODS: Eligible subjects aged 55-69â years, smokers or ex-smokers (at least 20 pack-years in the last 10â years), were randomised to receive an annual invitation for LDCT screening for 4â 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. RESULTS: 1613 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. CONCLUSIONS: Despite 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 NUMBER: Results, NCT02777996.
Subject(s)
Early Detection of Cancer/methods , Lung Neoplasms/diagnostic imaging , Aged , Female , Follow-Up Studies , Humans , Incidence , Italy/epidemiology , Kaplan-Meier Estimate , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Registries , Smoking/adverse effects , Smoking/epidemiology , Tomography, X-Ray Computed/methodsABSTRACT
In approaching the asbestos-related diseases with CT, both the malignant diseases and the non-malignant disease are to be considered. In the recent publication of the Helsinki Criteria research activities are encouraged in the field of lung cancer screening with low-dose CT (LDCT) in exposed workers and initiatives of data pooling and study protocols standardization are stimulated. Herein, we propose a review of the literature in the light of the Helsinki statement focused on the different techniques of imaging with CT and on the different fields of application in the asbestos-related disease.
Subject(s)
Occupational Exposure , Asbestos , Early Detection of Cancer , Humans , Italy , Lung Neoplasms/diagnosisABSTRACT
OBJECTIVES: To characterize early features of lung cancers detected with low-dose computed tomography (LDCT) screening. MATERIALS AND METHODS: Two radiologists reviewed prior LDCTs in 20 incident cancers diagnosed at annual repeat screening rounds and 83 benign nodules observed in the ITALUNG trial. RESULTS: No abnormality was observed in 3 cancers. Focal abnormalities in prior LDCT were identified in 17(85%) cancers (14 adenocarcinomas; 14 stage I). Initial abnormalities were intra-pulmonary in 10, subpleural in 4 and perifissural in 3. Average mean diameter was 9mm (range 4.5-18mm). Nine exhibited solid, 4 part-solid and 4 non-solid density. The margins were smooth and regular in 5 cases, lobulated in 6, irregular with spiculations in 3 and blurred in 3. Ten (59%) initial focal abnormalities had a round or oval nodular shape, but 7(41%) had a non-nodular complex (n=5) or "stripe-like" (n=2) shape. Bronchus sign was observed in 3 cases and association with cystic airspace in 2 cases. Non-solid density, complex or "stripe-like" shape, bronchus sign and association with cystic airspace had a specificity higher than 90%, but positive predictive value of every feature of incident lung cancers was low (range 10.4-50%). CONCLUSIONS: The vast majority of cancers diagnosed at annual repeat show corresponding focal lung abnormalities in prior LDCTs. Perifissural location and non-nodular shape do not exclude the possibility of early lung cancer. Since specificity of the early features of incident lung cancer is incomplete and their positive predictive value is low, all focal pulmonary abnormalities detected in screened subjects should be re-evaluated in subsequent LDCTs.
Subject(s)
Adenocarcinoma/diagnostic imaging , Early Detection of Cancer/methods , Lung Neoplasms/diagnostic imaging , Lymph Nodes/pathology , Tomography, X-Ray Computed , Adult , Aged , Female , Humans , Male , Neoplasm Staging , Randomized Controlled Trials as Topic , Sensitivity and Specificity , Tomography, X-Ray Computed/methodsABSTRACT
INTRODUCTION: 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. METHODS: 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-[18F]fluoro-2-deoxy-D glucose positron emission tomography (FDG-PET), and CT-guided fine-needle aspiration biopsy (FNAB). RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Adenocarcinoma/diagnosis , Carcinoma, Non-Small-Cell Lung/diagnosis , Early Detection of Cancer , Lung Neoplasms/diagnosis , Lymph Nodes/pathology , Small Cell Lung Carcinoma/diagnosis , Tomography, X-Ray Computed , Adenocarcinoma/surgery , Aged , Biopsy, Fine-Needle , Carcinoma, Non-Small-Cell Lung/surgery , Case-Control Studies , Female , Fluorodeoxyglucose F18 , Follow-Up Studies , Humans , Lung Neoplasms/surgery , Lymph Nodes/surgery , Male , Middle Aged , Neoplasm Staging , Positron-Emission Tomography , Prognosis , Radiopharmaceuticals , Small Cell Lung Carcinoma/surgery , Time FactorsABSTRACT
One of the most important problems in the segmentation of lung nodules in CT imaging arises from possible attachments occurring between nodules and other lung structures, such as vessels or pleura. In this report, we address the problem of vessels attachments by proposing an automated correction method applied to an initial rough segmentation of the lung nodule. The method is based on a local shape analysis of the initial segmentation making use of 3-D geodesic distance map representations. The correction method has the advantage that it locally refines the nodule segmentation along recognized vessel attachments only, without modifying the nodule boundary elsewhere. The method was tested using a simple initial rough segmentation, obtained by a fixed image thresholding. The validation of the complete segmentation algorithm was carried out on small lung nodules, identified in the ITALUNG screening trial and on small nodules of the lung image database consortium (LIDC) dataset. In fully automated mode, 217/256 (84.8%) lung nodules of ITALUNG and 139/157 (88.5%) individual marks of lung nodules of LIDC were correctly outlined and an excellent reproducibility was also observed. By using an additional interactive mode, based on a controlled manual interaction, 233/256 (91.0%) lung nodules of ITALUNG and 144/157 (91.7%) individual marks of lung nodules of LIDC were overall correctly segmented. The proposed correction method could also be usefully applied to any existent nodule segmentation algorithm for improving the segmentation quality of juxta-vascular nodules.
Subject(s)
Image Processing, Computer-Assisted/methods , Lung Neoplasms/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted/methods , Tomography, X-Ray Computed/methods , Databases, Factual , Humans , Reproducibility of ResultsABSTRACT
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 5mm), the reason of recall for all suspects at CT Scan (chi(2): 22.9; P<0.0001). Allelic imbalance showed good performance for screening of NCN > or = 5 mm. In subjects recalled for NCN > or = 5 mm, LOH, K-ras mutations and high levels of free plasma DNA (>5ng/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.