Lung Cancer Screening with Low-Dose CT: What We Have Learned in Two Decades of ITALUNG and What Is Yet to Be Addressed.

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.

Pulmonary emphysema and coronary artery calcifications at baseline LDCT and long-term mortality in smokers and former smokers of the ITALUNG screening trial.

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.

Low-dose CT for lung cancer screening: position paper from the Italian college of thoracic radiology.

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.

Lung ultrasound B-lines in systemic sclerosis: cut-off values and methodological indications for interstitial lung disease screening.

OBJECTIVES: Lung ultrasound (LUS), through assessment of B-lines and pleural line alterations, is able to evaluate interstitial lung disease (ILD), a frequent complication of SSc. Different scanning schemes and counting methods have been proposed but no clear cut-off values have been indicated for screening. We aimed to evaluate the accuracy of different LUS methodological approaches to detect ILD compared with high-resolution CT (HRCT) as the gold standard. METHODS: Sixty-nine SSc patients underwent LUS and chest HRCT on the same day. Both exams were scored by expert readers. The accuracy of different scanning schemes and counting methods was assessed and clinical and functional data were compared with imaging findings. RESULTS: B-lines were more numerous in patients with the diffuse skin subset and Scl70 autoantibody positivity. The number of B-lines correlated with the Scleroderma Lung Study (SLS) I HRCT score (R = 0.754, P < 0.0001). A total of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest showed 97% sensitivity for detecting even very early ILD signs (corresponding to an SLS I score of 1). Sensitivity increased to 100% when pleural line alterations were included in the analysis. CONCLUSIONS: LUS has a very high sensitivity in detecting SSc-related ILD. A cut-off value of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest can be used for the screening of SSc-ILD. Assessing only the postero-basal chest seems to be mostly effective, combining high sensitivity with a less time-consuming approach.

Moderate-severe coronary calcification predicts long-term cardiovascular death in CT lung cancer screening: The ITALUNG trial.

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.

Prognostic selection and long-term survival analysis to assess overdiagnosis risk in lung cancer screening randomized trials.

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.

Lung magnetic resonance imaging in systemic sclerosis: a new promising approach to evaluate pulmonary involvement and progression.

INTRODUCTION/OBJECTIVES: Interstitial lung disease (ILD) is frequent and highly disabling in systemic sclerosis (SSc). Magnetic resonance imaging (MRI) is not routinely used to evaluate the lung, due to poorer spatial resolution compared to high-resolution computed tomography (HRCT). We aimed to compare lung MRI signal with HRCT and evaluate the role of MRI in predicting ILD progression. METHODS: Thirty SSc patients underwent lung MRI and HRCT. STIR and T1 mapping sequences were acquired before and after gadolinium injection. Patients were classified as normal (group 1 with normal HRCT and MRI), discordant (group 2 without ILD signs on HRCT but areas of hyperintensity on MRI), and abnormal (group 3 with ILD signs on HRCT and areas of hyperintensity on MRI). Patients were followed up for ILD progression. RESULTS: Mean STIR and T1 values were different between the three groups (p < 0.0001). STIR values correlated with HRCT score (R = 0.79, p < 0.0001), lung ultrasound B-lines (R = 0.73, p < 0.0001), and %DLco (R = - 0.63, p = 0.0001). Nine events were recorded during a follow-up of 25 ± 20 months. Continuous STIR values were independently associated with events (HR 1.018; CI 1.005-1.031, p = 0.005). A STIR value >90 ms discriminated patients at a higher risk of worsening pulmonary involvement (HR 8.80; CI 1.81-42.74; p < 0.007). CONCLUSIONS: Lung MRI can detect SSc-related ILD, with good correlations with other ILD markers. STIR values, independently of HRCT appearance, may predict worsening lung involvement. Lung MRI, although very preliminary, is a promising tool that in a near future could help selecting patients for an early treatment of SSc-related ILD and a more appropriate use of HRCT. Key points • Lung MRI has the potential to differentiate inflammation-predominant versus fibrosis-predominant lesions, but it is not currently used in routine clinical practice to assess SSc-related ILD. • Lung MRI STIR and T1 values are significantly different between patients with and without SSc-related ILD. STIR values, independently of HRCT appearance, are also able to predict worsening lung involvement over time. • These preliminary data suggest that, in a near future, MRI could support the choice for an early treatment of SSc-related ILD, as well as a more appropriate use of HRCT.

Prognostic Value of Lung Ultrasound B-Lines in Systemic Sclerosis.

BACKGROUND: A high percentage of systemic sclerosis (SSc) patients experience interstitial lung disease (ILD) during the disease course. Recent data have shown that lung ultrasound (LUS) can assess ILD by the evaluation of B-lines, the sonographic sign of pulmonary interstitial involvement. RESEARCH QUESTION: To establish the prognostic value of B-lines in a large number of patients with SSc. STUDY DESIGN AND METHODS: A total of 396 consecutive patients with SSc, who were enrolled at three Rheumatology Departments, underwent a comprehensive LUS examination on the anterolateral and posterior chest for a total of 58 scanning sites. All available clinical, imaging, and functional data were recorded. Patients were followed after enrolment to establish the prognostic role of LUS. RESULTS: The median number of B-lines was higher in patients with the diffuse cutaneous subset (44 vs 17 B-lines; P < .0001), topoisomerase I autoantibodies (39 vs 16 B-lines; P < .0001), and the presence of ILD at chest high-resolution CT (45 vs 9 B-lines; P < .0001). At multivariable analysis, the number of posterior B-lines ≥5 was associated with new development or worsening ILD (hazard ratio, 3.378; 95% CI, 1.137-9.994; P = .028), with additional value over topoisomerase I positivity. The prognostic value was further confirmed in the subgroup of patients with known ILD at baseline (hazard ratio, 1.010; 95% CI, 1.003-1.018; P = .008). INTERPRETATION: Lung ultrasound B-lines are associated with worsening or development of pulmonary deterioration. In the near future, LUS might become part of the diagnostic and prognostic armamentarium in patients with SSc, which would allow a more sustainable and user-friendly approach to this very fragile population.

Automated Computed Tomography analysis in the assessment of Idiopathic Pulmonary Fibrosis severity and progression.

PURPOSE: To investigate the role of a quantitative analysis software (CALIPER) in identifying HRCT thresholds predicting IPF patients' survival and lung function decline and its role in detecting changes of HRCT abnormalities related to treatment and their correlation with Forced Vital Capacity (FVC). METHODS: This retrospective study included 105 patients with a multidisciplinary diagnosis of IPF for whom one HRCT at baseline and concomitant FVC were available. HRCTs were evaluated with CALIPER and the correlation between FVC and radiological features were assessed. Radiological thresholds for survival prediction and functional decline were calculated for all patients. Fifty-nine patients with at least 2 serial HRCTs were classified into two groups based on treatment. For patients for whom a FVC within 3 months of the HRCT was available (n = 44), the correlation of radiological and clinical progression was evaluated. RESULTS: The correlation between FVC and CALIPER-derived features at baseline was significant and strong. A baseline CALIPER-derived interstitial lung disease (ILD%) extent higher than 20 % and pulmonary vascular related structures (PVRS%) score greater than 5 % defined a worse prognosis. A significant progression of CALIPER-derived features in all patients was found with a faster increase in untreated patients. ILD% and PVRS% changes during follow-up demonstrated strong correlations with FVC changes. CONCLUSIONS: CALIPER quantification of fibrosis and vascular involvement could distinguish disease progression in treated versus untreated patients and predict the survival. The changes in CALIPER-derived variables over time were significantly correlated to changes in FVC.

Smoking Cessation in the ITALUNG Lung Cancer Screening: What Does "Teachable Moment" Mean?

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.

Decreased cardiovascular mortality in the ITALUNG lung cancer screening trial: Analysis of underlying factors.

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; p = 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.

Endothelial Cell-Derived Extracellular Vesicles as Potential Biomarkers in Chronic Interstitial Lung Diseases.

We investigated the potential role of extracellular vesicles as biomarkers in interstitial lung diseases. Endothelial derived extracellular vesicles were enumerated in 14 consecutive patients with usual interstitial pneumonia or possible usual interstitial pneumonia, and 18 normal controls by flow cytometry. The number of endothelial derived extracellular vesicles was significantly greater in patients compared to controls [160 (73) vs. 85 (31) events/min respectively; median (interquartile range); p<0.001]. A receiving operating characteristic curve shows that an arbitrary cut-off of 104 events/min corresponded to a sensitivity of 93%, and a specificity of 83%. Endothelial cell derived extracellular vesicles are potential biomarkers for the diagnosis of interstitial lung diseases.

3 T MR perfusion of solid pancreatic lesions using dynamic contrast-enhanced DISCO sequence: Usefulness of qualitative and quantitative analyses in a pilot study.

PURPOSE: To assess the usefulness of qualitative and quantitative analyses of pancreatic focal diseases by using the dynamic contrast-enhanced Differential Subsampling with Cartesian Ordering (DISCO) sequence at 3 T MR device. MATERIALS AND METHODS: Ten patients without pancreatic diseases and twenty-five patients with pathologically confirmed pancreatic focal disease (ductal adenocarcinoma, n = 14; endocrine tumour, n = 8; focal chronic pancreatitis, n = 3), underwent MRI by 3 T-device. Multiphasic contrast-enhanced MR perfusion, consisting of a 3D axial navigator, based free-breathing T1-weighted DISCO sequence, was repeated for 5 min. A dose of 0.1 mL/kg of Gadobutrolo with a 20 mL saline flush was injected at a flow rate of 5 mL/s. Perfusion MRI were processed using a dedicated software package (GeniQ; GE Healthcare), obtaining both a time-signal-intensity curve (TSIC) and perfusion maps for each healthy pancreatic parenchyma and focal disease. The TSIC were grouped into four types according to their shapes and the MR perfusion parameters (Ktrans, Kep, Ve, IAUGC) were calculated. The one-way analysis of variance and the Student's t-test were used to correlate the quantitative and qualitative parameters with the tissue histology. RESULTS: All 10 patients with healthy pancreas presented a TSIC-type 1; TSIC-type 2 was observed in all 14 ductal adenocarcinomas and in one neuroendocrine tumour; TSIC-type 3 was recognized in the remaining 7 neuroendocrine neoplasms; TSIC-type 4 was identified in all 3 focal chronic pancreatitis. All perfusion parameters were significantly different (p < 0.0001) for each type of lesion. Furthermore, Ve was also very useful to discriminate between normal and pathological tissues (p = 0.0005). CONCLUSION: Qualitative and quantitative analyses of contrast-enhanced 3 T MR perfusion, using the dynamic contrast-enhanced DISCO sequence, could be considered an interesting tool to improve the diagnosis of focal pancreatic diseases, of solid lesions in particular. Further investigations with prospective larger sample studies are required to confirm these preliminary results.

The use of chest magnetic resonance imaging in interstitial lung disease: a systematic review.

Thin-slices multi-detector computed tomography (MDCT) plays a key role in the differential diagnosis of interstitial lung disease (ILD). However, thin-slices MDCT has a limited ability to detect active inflammation, which is an important target of newly developed ILD drug therapy. Magnetic resonance imaging (MRI), thanks to its multi-parameter capability, provides better tissue characterisation than thin-slices MDCT.Our aim was to summarise the current status of MRI applications in ILD and to propose an ILD-MRI protocol. A systematic literature search was conducted for relevant studies on chest MRI in patients with ILD.We retrieved 1246 papers of which 55 original papers were selected for the review. We identified 24 studies comparing image quality of thin-slices MDCT and MRI using several MRI sequences. These studies described new MRI sequences to assess ILD parenchymal abnormalities, such as honeycombing, reticulation and ground-glass opacity. Thin-slices MDCT remains superior to MRI for morphological imaging. However, recent studies with ultra-short echo-time MRI showed image quality comparable to thin-slices MDCT. Several studies demonstrated the added value of chest MRI by using functional imaging, especially to detect and quantify inflammatory changes.We concluded that chest MRI could play a role in ILD patients to differentiate inflammatory and fibrotic changes and to assess efficacy of new ILD drugs.

Biliary complications after liver transplantation: Assessment with MR cholangiopancreatography and MR imaging at 3T device.

PURPOSE: Our study was aimed to assess the diagnostic value of MR cholangiopancreatography (MRCP) and MR imaging at 3 T device when evaluating biliary adverse events after liver transplantation. MATERIALS AND METHODS: A series of 384 MR examinations in 232 liver transplant subjects with suspected biliary complications (impaired liver function tests and/or biliary abnormalities on ultrasound) were performed at 3 T device (GE-DISCOVERY MR750; GE Healthcare). After the acquisition of axial 3D dual-echo T1-weighted images and T2-weighted sequences (propeller and SS-FSE), MRCP was performed through coronal thin-slab 3D-FRFSE and coronal oblique thick-slab SSFSE T2w sequences. DW-MRI of the liver was performed using an axial spin-echo echo-planar sequence with multiple b values (150, 500, 1000, 1500 s/mm2) in all diffusion directions. Contrast-enhanced MRCP was performed in 25/232 patients. All MR images were blindly evaluated by two experienced abdominal radiologists in consensus to determine the presence of biliary complications, whose final diagnosis was based on direct cholangiography, surgery and integrating clinical follow-up with ultrasound and/or MRI findings. RESULTS: In 113 patients no biliary abnormality was observed. The remaining 119 subjects were affected by one or more of the following complications: non-anastomotic strictures including typical ischemic-type biliary lesions (n = 67), anastomotic strictures (n = 34), ampullary dysfunction (n = 4), anastomotic leakage (n = 4), stones, sludge and casts (n = 65), vanishing bile duct (n = 1). The sensitivity, specificity, PPV, NPV and diagnostic accuracy of the reviewers for the detection of all types of biliary complications were 99%, 96%, 95%, 99% and 97%, respectively. CONCLUSION: MR cholangiopancreatography and MR imaging at 3 T device are extremely reliable for detecting biliary complications after liver transplantation.

Screen-detected multiple primary lung cancers in the ITALUNG trial.

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.

Imaging of malignant pleural mesothelioma: it is possible a screening or early diagnosis program?-a systematic review about the use of screening programs in a population of asbestos exposed workers.

Malignant pleural mesothelioma (MPM) in an uncommon neoplasia with high mortality rate, mostly related to professional asbestos exposure. Clinical manifestations are not specific so that diagnosis is performed at advanced stage and screening protocols are not feasible now. On the other hand, asbestos-exposed workers have a high incidence of developing lung cancer. Low-dose computed tomography (LDCT) is a volumetric acquisition technique with high spatial resolution and a low dose exposure; it is used in many trials to detect lung tumours at an early stage in screening protocols, reducing mortality rate in smoker subjects. In recent papers, the possibly role of lung cancer screening was evaluated and recommended also in subjects exposed to asbestos. This article summarizes previous and present clinical trials validated for lung cancer screening, to discuss the possibility of early diagnosis or screening programs in a population of asbestos exposed workers by LDCT.

Clinical Impact of Radioguided Localization in the Treatment of Solitary Pulmonary Nodule: A 20-Year Retrospective Analysis.

PURPOSE: Incidental solitary pulmonary nodules (SPNs) have become an increasingly common CT finding worldwide. Although there are currently many imaging strategies for evaluating SPNs, the differential diagnosis and management of SPNs remains complex because of overlap between benign and malignant processes. Moreover, transbronchial or percutaneous CT-guided biopsies do not always allow definitive diagnoses. In such cases, video-assisted thoracic surgery (VATS) has become the preferred surgical procedure for diagnosis and, in selected cases, for treatment of indeterminate SPNs. The difficulties in localizing smaller, deeper, and ground-glass nodules have been approached with different techniques. The aim of this study was to report 20 years of experience with radioguided thoracoscopic resection of SPNs at the Regional Centre of Nuclear Medicine of Pisa. METHODS: Three hundred ninety-five patients with SPNs less than 2 cm and deeper than 5 mm below the visceral pleura underwent CT-guided injection of a suspension composed of 0.1 to 0.2 mL Tc-labeled human albumin macroaggregates (Tc-MAA) and of 0.2 to 0.3 mL of nonionic contrast medium into or adjacent to the SPN. During VATS, the pulmonary area with the highest target/background ratio identified by an 11-mm-diameter collimated thoracoscopic gamma probe was resected. RESULTS: From 1997 to 2016, approximately 395 patients with SPN underwent VATS wedge resection using the radioguided technique. Mean SPN size was 13 mm (range, 5-20 mm) with mean distance of 15 mm (range, 6-39 mm) from the visceral pleura. Mean VATS procedural time was 40 minutes (range, 20-90 minutes), with an average time of 3 minutes (range, 1-5 minutes) to localize the nodule. Neither mortality nor major perioperative complication was reported. The success rate of VATS with radioguidance in our series was 99%. Histological examination revealed 206 benign lesions (52%), 59 primary lung tumors (15%), and 130 metastatic nodules (33%). CONCLUSIONS: This study demonstrates that radioguided SPN localization by VATS is a feasible, safe, and rapid procedure with highly successful rate of SPN resection.

3T diffusion-weighted MRI in the response assessment of colorectal liver metastases after chemotherapy: Correlation between ADC value and histological tumour regression grading.

PURPOSE: The purpose of the study was to correlate the apparent diffusion coefficient (ADC) values of diffusion-weighted MR imaging (DW-MRI) by 3T device with the histological tumour regression grading (TRG) analysis of colorectal liver metastases after preoperative chemotherapy. MATERIALS AND METHODS: Our study included thirty-five patients with colorectal liver metastases who had undergone MRI by 3T device (GE DISCOVERY MR750; GE Healthcare) after preoperative chemotherapy. DW-MRI was performed using a single-shot spin-echo echo-planar sequence with multiple b-values (0, 150, 500, 1000, 1500s/mm2), thus obtaining an ADC map. For each liver lesion (more than 1cm in diameter) the fitted ADC values were calculated by two radiologists in conference and three ROIs were drawn: around the entire tumour (ADCe), at the tumour periphery (ADCp) and at the tumour center (ADCc). All ADC values were correlated with histopathological findings after surgery. Hepatic metastases were pathologically classified into five groups on the basis of TRG. Statistical analysis was performed on a per-lesion basis utilizing the one-way analysis of variance (ANOVA). This retrospective study was approved by our institutional review board; written informed consent was obtained from all patients. RESULTS: A total of 106 colorectal liver metastases were included for image analysis. TRG1, TRG2, TRG3, TRG4 and TRG5 were observed in 4, 14, 36, 35 and 17 lesions, respectively. ADCe and ADCp values were significantly higher in lesions classified as TRG1 (2.40±0.12×10-9m2/s and 2.28±0.26×10-9m2/s, respectively) and as TRG2 (1.40±0.31×10-9m2/s and 1.44±0.35×10-9m2/s), compared to TRG3 (1.16±0.13×10-9m2/s and 1.01±0.18×10-9m2/s), TRG4 (1.10±0.26×10-9m2/s and 0.97±0.24×10-9m2/s), and TRG5 (0.93±0.17×10-9m2/s and 0.82±0.28×10-9m2/s). ADCe, ADCp and ADCc values were significantly different in TRG classes (p<0.0001). Statistical correlations were found between the ADCe, ADCp, ADCc values and the TRG classes (Spearman correlation coefficient were -0.568, -0.542 and -0.554, respectively). CONCLUSION: Our study showed a significant correlation between ADC values of 3T DW-MRI and histological TRG of colorectal liver metastases after preoperative chemotherapy.

Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial.

BACKGROUND: ITALUNG is contributing to the European evaluation of low-dose CT (LDCT) screening for lung cancer (LC). METHODS: Eligible 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. 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.