Search

Objectives: To assess the association between CT features and EGFR, ALK, KRAS mutations in non-small cell lung cancer.Methods: Patients undergoing chest CT and testing for the above gene mutations were included. Qualitative evaluation of CTs included: lobe; lesion diameter; shape; margins; ground-glass opacity; density; cavitation; air bronchogram; pleural thickening; intratumoral necrosis; nodules in tumour lobe; nodules in non-tumour lobes; pleural retraction; location; calcifications; emphysema; fibrosis; pleural contact; pleural effusion. Statistical analysis was performed to assess association of features with each gene mutation. ROC curves for gene mutations were drawn; the corresponding area under the curve was calculated. P-values <0.05 were considered significant.Results: Of 285 patients, 60/280 (21.43 %) were positive for EGFR mutation; 31/270 (11.48 %) for ALK rearrangement; 64/240 (26.67 %) for KRAS mutation. EGFR mutation was associated with air bronchogram, pleural retraction, females, non-smokers, small lesion size, and absence of fibrosis. ALK rearrangements were associated with age and pleural effusion. KRAS mutation was associated with round shape, nodules in non-tumour lobes, and smoking.Conclusions: This study disclosed associations between CT features and alterations of EGFR (air bronchogram, pleural retraction, small lesion size, absence of fibrosis), ALK (pleural effusion) and KRAS (round lesion shape, nodules in non-tumour lobes).Key Points: Air bronchogram, pleural retraction, small size relate to EGFR mutation in NSCLC. Pleural effusion and younger age relate to ALK mutation. Round lesion shape, nodules in non-tumour lobes relate to KRAS mutation. [ABSTRACT FROM AUTHOR]

Objectives: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure that has revolutionized the diagnosis and staging of lung cancer. The goal of the present study was to investigate the yield and applicability of molecular testing in the specimens obtained by EBUS-TBNA from patients with advanced non-small cell lung cancer (NSCLC), comparing the results with a series of patients who underwent diagnostic surgical procedures in the same institution.Methods: The study followed 306 consecutive patients with clinically diagnosed primary lung cancer who had the EBUS-TBNA procedure. EGFR and KRAS mutations were evaluated on cytologic specimens by Sanger sequencing and Cobas real-time polymerase chain reaction, whereas ALK rearrangement was tested by fluorescence in situ hybridization. The results were compared with those obtained from a series of 1,000 NSCLC surgical samples routinely analyzed.Results: Molecular testing was possible in 96.9% of the samples obtained by EBUS-TBNA. EGFR (exons 18-21) mutations were found in 16.9%, KRAS mutation (exons 2-3) in 31.6%, and ALK rearrangement in 3.9% of the cases. In the surgical series, the mutations' distribution were 14.8%, 29.0%, and 3.4%, respectively. There were no statistical differences between the two series.Conclusions: Our study demonstrates that EBUS-TBNA can be effectively used not just for diagnosis but also for complete mutational testing. [ABSTRACT FROM AUTHOR]

Simple Summary: Preoperative results of the 6-min walking test help to identify risk of postoperative complications and increased mortality in patients undergoing lobectomy for lung cancer. The aim of the study was to validate the value of 500 m in 6MWT as an indicator, which differentiates risk of complications in patients undergoing pneumonectomy. 125 patients who underwent pneumonectomy at Thoracic Surgery Department between 2009 and 2018. Additionally, on the day before the surgery, patients performed the 6-min walking test. We analyzed 93 men and 32 women with a median age of 63 years. The cut-off value of 500 m identified patients with increased 90-day mortality, first-year mortality, and overall survival. Patients who covered a distance ≤ 500 m had an increased risk of atrial fibrillation and cardiac complications. Patients who do not reach the distance of 500 m in 6-min walking test have a high risk of early postoperative death after pneumonectomy. Due to its debilitating character pneumonectomy this is last-resort procedure. Preoperative results of the 6-min walking test (6MWT) help to identify high risk of postoperative complications and increased mortality in patients undergoing lobectomy for lung cancer. The aim of the study was to validate the value of 500 m in 6MWT as an indicator, which differentiates risk of complications in patients undergoing pneumonectomy. 125 patients who underwent pneumonectomy at Thoracic Surgery Department between 2009 and 2018. On the day preceding the surgery, patients underwent 6MWT. The patients were in median age of 63 years. The cut-off value of 500 m identified patients with increased 90-day mortality [17.9% vs. 3.5%, odds ratio (OR) 6.271, 95% confidence interval (CI) 1.528–25.739], first-year mortality (30.7% vs. 11.6%, OR 3.378, 95% CI 1.310–8.709), and overall survival (p = 0.02). Patients who covered a distance ≤ 500 m had an increased risk of atrial fibrillation (35.9% vs. 16.3%, OR 2.880, 95% CI 1.207–6.870) and cardiac complications (38.4% vs. 19.8%, OR 2.537, 95% CI 1.100–5.849). Patients unable to reach 500 m in 6MWT are in a high risk of postoperative death after pneumonectomy, what may be a result of increased frequency of postoperative cardiac complications. Poor result of 6MWT is a predictor of worse overall survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Evaluation of the prognostic significance of serial measurements of serum concentrations of Krebs von den Lungen-6 (KL-6) showed that an annual increment in KL-6 exceeding a threshold amount was an independent risk factor for progressive disease and poor prognosis. No literature data are available on long-term KL-6 measurements in the follow-up of IPF patients treated with Nintedanib. The aim of this study is to serially analyze KL-6 in idiopathic pulmonary fibrosis (IPF) patients after 24 months of Nintedanib and to investigate its biomarker potential in patients with IPF and lung cancer with respect to fibrotic hypersensitivity pneumonitis patients, pulmonary fibrosis associated with autoimmune diseases group and healthy controls. Background: Krebs von den Lungen-6 (KL-6) was suggested as ILD biomarker including idiopathic pulmonary fibrosis (IPF). Lung cancer is one of the most severe comorbidity of IPF patients. This study aims to serially analyze KL-6 in IPF patients after 24 months of Nintedanib and to first investigate the biomarker behavior in IPF associated with adenocarcinoma. Materials and methods: One hundred and forty-two ILD patients (median (IQR), 69 (63–75) years; 86 males) were retrospectively enrolled. Serial serum samples were collected from IPF patients before starting antifibrotic therapy and after 12 months. Serum KL-6 levels were measured by KL-6 reagent assay (Fujirebio Europe, UK). Results: Increased KL-6 concentrations were identified in IPF-LC patients than IPF, fibrotic hypersensitivity pneumonitis, and pulmonary fibrosis associated with autoimmune disease groups. A cut-off value was calculated to distinguish IPF and IPF-LC patients. IPF patients monitored for 24 months with Nintedanib showed persisted increased levels of KL-6 with a progressive decline of FVC percentages. Conclusion: This preliminary study offers a first demonstration that very high serum concentrations of KL-6 in IPF-LC patients are associated with poor prognosis. Moreover, serial evaluation of serum KL-6 in IPF patients over 24 months of Nintedanib treatment revealed that most patients experienced a stabilization of lung function parameters and of serum concentrations of KL-6. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper is a review of the literature on the clinical role of oncomarkers in idiopathic pulmonary fibrosis (IPF) progression, and a description of the routine oncomarker trend in IPF patients over the longest follow-up yet reported. This is the first meta-analysis to review the results of studies evaluating the predictive prognostic value of circulating oncomarkers (CEA, Ca15.3, Ca19.9, Ca125, and KL-6) for IPF. The study focused on the discovery of multiple biomarker signatures, such as combinations of oncomarkers, that are widely and routinely available in biochemistry laboratories. The combination of clinical parameters and biological markers could help achieve more accurate results regarding prognosis and response to treatment in IPF. Our results could pave the way for a more "personalized" medical approach to patients affected by IPF. Background: Idiopathic pulmonary fibrosis (IPF) is a severe progressive interstitial lung disease. At 5-year follow-up, 15% of IPF patients develop lung cancer, which significantly reduces the survival rate. Here we review the literature on the clinical role of oncomarkers in IPF progression, and describe the trend of routine oncomarkers in IPF patients over the longest follow-up yet reported. Materials and methods: A systematic search of the literature in PubMed was performed to find relevant studies published up to 24 September 2020. The most common oncomarkers were chosen to select papers related to pulmonary fibrosis. Then, 24 IPF patients and 25 non-IPF patients, followed at Careggi ILD Referral Centre and Siena Regional Referral Centre for ILD, were enrolled consecutively. Results: A few studies reported an association between serum oncomarkers and severity of IPF. NSE, CEA, Ca19.9, and Ca125 were higher in the IPF, than in the non-IPF, group at every follow-up (p < 0.05). Ca15.3 concentrations were higher in the IPF, than the non-IPF, group at t3 (p = 0.0080) and t4 (p = 0.0168). To improve the specificity and sensitivity of Ca15.3, a panel of biomarkers was analyzed, with the IPF group as dependent variable, and chitotriosidase, Cyfra 21.1, Ca15.3, Ca125, and Ca19.9 as independent variables. Conclusions: This study focused on the discovery of multiple biomarker signatures, such as combinations of oncomarkers, that are widely and routinely available in biochemistry laboratories. The combination of clinical parameters and biological markers could help achieve more accurate results regarding prognosis and response to treatment in IPF. Our results could pave the way for a more "personalized" medical approach to patients affected by IPF. [ABSTRACT FROM AUTHOR]

Summary: Detailed studies on the pathologic and molecular features of low-dose computed tomography (LDCT)-detected carcinomas and comparison with unscreened tumors are still lacking. We evaluated the histopathologic features of 89 LDCT-detected lung cancers resected between 2004 and 2006. These tumors occurred within a cohort of 5202 volunteers undergoing annual LDCT, aged ≥50 years, and with a minimum 20 pack-year index. In adenocarcinomas, central scar diameter, invasion foci size and K-ras mutations were also assessed. The results were compared with those of 89 consecutive lung carcinomas matched for confounding factors (sex, smoking habit), selected from group of 363 consecutive clinically worked-up lung cancer, surgically resected in the same period and at the same Institution. The tumors were diagnosed in 63 males and 26 females (range 50–79 years), 55 of which diagnosed at the baseline (1.05%) and 34 (including 10 repeat cancers) operated after work-up during the second year (0.72%). LDCT-detected tumors showed high resectability rate (89%), earlier stage (63%) and prevalence of adenocarcinoma nodules (72%), most often of the mixed subtype, in comparison with unscreened tumors. A similar prevalence of K-ras mutations was found in both screened and unscreened adenocarcinomas. Repeat cancers were found in 10 screened patients, and were predominantly stage I adenocarcinomas of mixed subtype exhibiting smaller dimension but greater central scar diameter and stromal invasion size in comparison with the other second-year, slower-growing adenocarcinomas. Multiple tumor nodules were identified in 10 patients exclusively at the baseline, were mostly mixed adenocarcinomas and differed in their K-ras mutation profile. Screening-detected lung cancers shared most of the histologic features of fully malignant tumors, in addition to a similar prevalence of K-ras mutations, despite their earlier detection and less advanced clinical stage. Repeat cancers are potentially aggressive tumors. K-ras mutation analysis supports the impression that multifocal tumors at baseline are separate synchronous primaries. [Copyright &y& Elsevier]