Evaluation of Conventional Cardiovascular Risk Factors and Ordinal Coronary Artery Calcium Scoring in a Lung Cancer Screening Cohort.

(1) Background: Lung cancer screening (LCS) consists of low-dose computed tomography (LDCT) results to reduce lung cancer-related mortality. The LCS program has a unique opportunity to impact CVD mortality by providing tools for CVD risk assessment and implementing preventative strategies. In this study, we estimated standardized CVD risk (SCORE) and assessed the prevalence of coronary artery calcium (CAC) in a Polish LCS cohort. (2) Methods: In this observational study, 494 LCS participants aged 50-79 years with a cigarette smoking history of at least 30 pack-years were included. Medical history, anthropometric measurements, blood pressure measurements, serum glucose, and cholesterol levels were assessed in one visit. CVD risk assessment using SCORE tables was performed. The results were compared to the general population (NATPOL 2011 study). On LDCT scans, CAC was classified using an Ordinal Score ranging from 0 to 12. (3) Results: The prevalence of classic cardiovascular risk factors was very high. Among study participants, 83.7% of men and 40.7% of women were classified with a very high CVD SCORE risk (>10%). CAC was reported in 190 (47%) participants. Calcification was categorized as severe (CAC ≥ 4) in 84 (21%) participants. (4) Conclusions: Due to the high cardiovascular risk, intensive preventive strategies are recommended for LCS participants.

Efficacy and Safety of Gadopiclenol for Contrast-Enhanced MRI of the Central Nervous System: The PICTURE Randomized Clinical Trial.

OBJECTIVES: Developing new high relaxivity gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) allowing dose reduction while maintaining similar diagnostic efficacy is needed, especially in the context of gadolinium retention in tissues. This study aimed to demonstrate that contrast-enhanced MRI of the central nervous system (CNS) with gadopiclenol at 0.05 mmol/kg is not inferior to gadobutrol at 0.1 mmol/kg, and superior to unenhanced MRI. MATERIALS AND METHODS: PICTURE is an international, randomized, double-blinded, controlled, cross-over, phase III study, conducted between June 2019 and September 2020. Adult patients with CNS lesions were randomized to undergo 2 MRIs (interval, 2-14 days) with gadopiclenol (0.05 mmol/kg) then gadobutrol (0.1 mmol/kg) or vice versa. The primary criterion was lesion visualization based on 3 parameters (border delineation, internal morphology, and contrast enhancement), assessed by 3 off-site blinded readers. Key secondary outcomes included lesion-to-background ratio, enhancement percentage, contrast-to-noise ratio, overall diagnostic preference, and adverse events. RESULTS: Of the 256 randomized patients, 250 received at least 1 GBCA administration (mean [SD] age, 57.2 [13.8] years; 53.6% women). The statistical noninferiority of gadopiclenol (0.05 mmol/kg) to gadobutrol (0.1 mmol/kg) was achieved for all parameters and all readers (n = 236, lower limit 95% confidence interval of the difference ≥-0.06, above the noninferiority margin [-0.35], P < 0.0001), as well as its statistical superiority over unenhanced images (n = 239, lower limit 95% confidence interval of the difference ≥1.29, P < 0.0001).Enhancement percentage and lesion-to-background ratio were higher with gadopiclenol for all readers ( P < 0.0001), and contrast-to-noise ratio was higher for 2 readers ( P = 0.02 and P < 0.0001). Three blinded readers preferred images with gadopiclenol for 44.8%, 54.4%, and 57.3% of evaluations, reported no preference for 40.7%, 21.6%, and 23.2%, and preferred images with gadobutrol for 14.5%, 24.1%, and 19.5% ( P < 0.001).Adverse events reported after MRI were similar for gadopiclenol (14.6% of patients) and gadobutrol (17.6%). Adverse events considered related to gadopiclenol (4.9%) and gadobutrol (6.9%) were mainly injection site reactions, and none was serious. CONCLUSIONS: Gadopiclenol at 0.05 mmol/kg is not inferior to gadobutrol at 0.1 mmol/kg for MRI of the CNS, confirming that gadopiclenol can be used at half the gadolinium dose used for other GBCAs to achieve similar clinical efficacy.

Combining Low-Dose Computer-Tomography-Based Radiomics and Serum Metabolomics for Diagnosis of Malignant Nodules in Participants of Lung Cancer Screening Studies.

Radiomics is an emerging approach to support the diagnosis of pulmonary nodules detected via low-dose computed tomography lung cancer screening. Serum metabolome is a promising source of auxiliary biomarkers that could help enhance the precision of lung cancer diagnosis in CT-based screening. Thus, we aimed to verify whether the combination of these two techniques, which provides local/morphological and systemic/molecular features of disease at the same time, increases the performance of lung cancer classification models. The collected cohort consists of 1086 patients with radiomic and 246 patients with serum metabolomic evaluations. Different machine learning techniques, i.e., random forest and logistic regression were applied for each omics. Next, model predictions were combined with various integration methods to create a final model. The best single omics models were characterized by an AUC of 83% in radiomics and 60% in serum metabolomics. The model integration only slightly increased the performance of the combined model (AUC equal to 85%), which was not statistically significant. We concluded that radiomics itself has a good ability to discriminate lung cancer from benign lesions. However, additional research is needed to test whether its combination with other molecular assessments would further improve the diagnosis of screening-detected lung nodules.

Pulmonary nodule radiological diagnostic algorithm in lung cancer screening.

Publications of the final results of the two largest randomized lung cancer screening (LCS) trials in the United States and Europe confirmed the reduction in the mortality rate associated with the use of screening with low-dose computed tomography (LDCT). Results of these trials led to widespread acceptance of LCS in properly defined high-risk populations, and its implementation in the clinical practice. Many countries started preparation for national LCS and refreshed still open debate about lung nodule management. Detection of lung cancer in the early stage with a reduction of lung cancer mortality requires dedicated programs with optimized protocols, including a specified pulmonary nodule diagnostic algorithm. The screening protocol should be clear with a precise nodule diameter or volume threshold, based on which a positive screen result is defined. The application of risk-prediction models and the introduction of the semiautomated assessment of detected nodules improves screening accuracy and should be applied in LCS protocols as verified tools to aid radiological diagnosis. In this review, we have summarized recent data about the radiological protocols from the most important LCS programs and pulmonary diagnostic algorithms. These protocols should be taken into consideration in the ongoing and planned LCS programs.

Emphysema - The review of radiological presentation and its clinical impact in the LDCT screening era.

Emphysema is one of three main lung pathologies in Chronic Obstructive Pulmonary Disease, along with chronic bronchitis and small airway obstruction. The diagnosis is based on detection of low attenuation areas in lung tissue on chest Computed Tomography, either visual by a radiologist, or automatic by the applied Computed Tomography software. Results of the studies on the association between emphysema and lung cancer incidence are mixed. Many studies have demonstrated, that chronic lung diseases, like Chronic Obstructive Pulmonary Disease, are associated with lung cancer morbidity. There is also evidence, that emphysema can be related with worse prognosis in patients with detected lung cancer. In this review article we aim to summarize current knowledge about emphysema detection and evaluation on Computed Tomography, both quantitative and qualitative. We also summarize current data on correlation between emphysema and lung cancer, as well as its potential use in selecting patients, who would most benefit from lung cancer screening.

Ten years of experience in lung cancer screening in Gdansk, Poland: a comparative study of the evaluation and surgical treatment of 14 200 participants of 2 lung cancer screening programmes†.

OBJECTIVES: The European Society of Thoracic Surgeons' recommendations confirm the implementation of lung cancer screening in Europe. We compared 2 screening programmes, the Pilot Pomeranian Lung Cancer Screening Programme (pilot study) and the Moltest Bis programme, completed in a single centre. METHODS: A total of 8649 healthy volunteers (aged 50-75 years, smoking history ≥20 pack-years) were enrolled in a pilot study between 2009 and 2011, and a total of 5534 healthy volunteers (aged 50-79, smoking history ≥30 pack-years) were enrolled in the Moltest Bis programme between 2016 and 2017. Each participant had a low-dose computed tomography scan of the chest. Participants with a nodule diameter of >10 mm or with suspected tumour morphology underwent a diagnostic work-up in the pilot study. In the Moltest Bis programme, the criteria were based on the volume of the detected nodule on the baseline low-dose computed tomography scan and the volume doubling time in the subsequent rounds. RESULTS: Lung cancer was diagnosed in 107 (1.24%) and 105 (1.90%) participants of the pilot study and of the Moltest Bis programme, respectively (P = 0.002). A total of 300 (3.5%) and 199 (3.6%) patients, respectively, were referred for further invasive diagnostic work-ups (P = 0.69). A total of 125 (1.5%) and 80 (1.5%) patients, respectively, underwent surgical resection (P = 0.74). The number of resected benign lesions was similar: 44 (35.0%) and 20 (25.0%), respectively (P = 0.13), but with a downwards trend. Lobectomies and/or segmentectomies were performed in 84.0% and 90.0% of patients with lung cancer, respectively (P = 0.22). Notably, patients in the Moltest Bis programme underwent video-assisted thoracoscopic surgery more often than did those in the pilot study (72.5% vs 24.0%, P < 0.001). Surgical patients with stages I and II non-small-cell lung cancer (NSCLC) accounted for 83.4% of the Moltest patients and 86.4% of the pilot study patients (P = 0.44). CONCLUSIONS: Modified inclusion criteria in the screening programme lead to a higher detection rate of NSCLC. Growing expertise in lung cancer screening leads to increased indications for minimally invasive surgery and an increased proportion of lung-sparing resections. A single-team experience in lung cancer screening does not lead to a major reduction in the rate of diagnostic procedures and operations for non-malignant lesions.

Efficacy comparison of multi-phase CT and hepatotropic contrast-enhanced MRI in the differential diagnosis of focal nodular hyperplasia: a prospective cohort study.

BACKGROUND: Different clinical behaviour influences the importance of differentiating focal nodular hyperplasia (FNH) from other focal liver lesions (FLLs). The aim of this study was to compare the efficacy of contrast-enhanced CT and MRI in the diagnosis of FNH. METHODS: 157 patients with equivocal FLLs detected in ultrasonography subsequently underwent multi-phase CT and MRI with the use of hepatotropic contrast agent (Gd-BOPTA) in a 1.5 T scanner. Examinations were evaluated by three independent readers. Diagnostic efficacy of different radiological signs of FNH in both CT and MRI was compared and AFROC analysis was performed. RESULTS: 4 hepatocellular adenomas, 95 hepatocellular carcinomas, 98 hemangiomas, 138 metastases and 45 FNHs were diagnosed. In both CT and MRI the radiological sign of the highest accuracy was the presence of the central scar within FNH (0.93 and 0.96 relatively). The sum of two radiological signs in MRI: homogeneous enhancement in hepatic arterial phase (HAP) and enhancing lesion in hepatobiliary phase (HBP) was characterized with high values of sensitivity (0.89), specificity (0.97), PPV (0.82), NPV (0.98) and accuracy (0.96). After inclusion of clinical data into analysis the best discriminating feature in MRI was the presence of enhancing lesion in HBP in patients without cirrhosis. In this regard, efficacy parameters increased to 1.00, 0.99, 0.94, 1.00 and 0.99 accordingly. The area under the curve in AFROC analysis of MRI performance was significantly larger than of CT (p = 0.0145). CONCLUSION: Gd-BOPTA-enhanced MRI is a more effective method in the differential diagnosis of FNH than multi-phase CT.

Insulin-like growth factor receptor 1 (IGF1R) gene copy number is associated with survival in operable non-small-cell lung cancer: a comparison between IGF1R fluorescent in situ hybridization, protein expression, and mRNA expression.

PURPOSE: The purpose of this study was to characterize insulin-like growth factor-1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non-small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis. PATIENTS AND METHODS: One hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n = 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh-frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n = 181). RESULTS: IGF1R IHC score was higher in squamous cell carcinomas versus other histologies (P < .001) and associated with stage (P = .03) but not survival (P = .46). IGF1R and EGFR protein expression showed significant correlation (r = 0.30; P < .001). IGF1R gene expression by qRT-PCR was higher in squamous cell versus other histologies (P = .006) and did not associate with other clinical features nor survival (P = .73). Employing criteria previously established for EGFR copy number, patients with IGF1R amplification/high polysomy (n = 48; 27%) had 3-year survival of 58%, patients with low polysomy (n = 87; 48%) had 3-year survival of 47% and patients with trisomy/disomy (n = 46; 25%) had 3-year survival of 35%, respectively (P = .024). Prognostic value of high IGF1R gene copy number was confirmed in multivariate analysis. CONCLUSION: IGF1R protein expression is higher in squamous cell versus other histologies and correlates with EGFR expression. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value.