Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression.

Non-small cell cancer (NSCLC) has been identified with a great variation of mutations that can be surveyed during disease progression. The aim of the study was to identify and monitor lung cancer-specific mutations incidence in cell-free DNA as well as overall plasma cell-free DNA load by means of targeted next-generation sequencing. Sequencing libraries were prepared from cell-free DNA (cfDNA) isolated from 72 plasma samples of 41 patients using the Oncomine Lung cfDNA panel covering hot spot regions of 11 genes. Sequencing was performed with the Ion Torrent™ Ion S5™ system. Four genes were detected with highest mutation incidence: KRAS (43.9% of all cases), followed by ALK (36.6%), TP53 (31.7%), and PIK3CA (29.3%). Seven patients had co-occurring KRAS + TP53 (6/41, 14.6%) or KRAS + PIK3CA (7/41, 17.1%) mutations. Moreover, the mutational status of TP53 as well an overall cell-free DNA load were confirmed to be predictors of poor progression-free survival (HR = 2.5 [0.8-7.7]; p = 0.029 and HR = 2.3 [0.9-5.5]; p = 0.029, respectively) in NSCLC patients. In addition, TP53 mutation status significantly predicts shorter overall survival (HR = 3.4 [1.2-9.7]; p < 0.001). We demonstrated that TP53 mutation incidence as well as a cell-free DNA load can be used as biomarkers for NSCLC monitoring and can help to detect the disease progression prior to radiological confirmation of the status.

Lung Cancer Survival in Lithuania: Changes by Histology, Age, and Sex From 2003-2007 to 2008-2012.

Lung cancer is the most common cancer-related death worldwide. The aim of this study is to describe the most recent survival rates by sex, age group, extent of disease, and histology of lung cancer in Lithuania. The study is based on the Lithuanian Cancer Registry database. The analysis included patients with primary invasive lung cancer diagnosed in 1998 to 2012 (International Classification of Diseases, Tenth Revision C33 and C34). Patients were followed up with respect to vital status until December 31, 2012. Five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of patients with cancer and the expected survival of the underlying general population. In our study, the overall 5-year relative survival was low but increased slightly (10.7%) from 2003-2007 to 2008-2012. Positive changes in survival were evident in both sexes, in almost all age groups and for all histological groups and disease stages. Adenocarcinoma relative survival increased from 6.7% in 2003-2007 to 12.8% in 2008-2012 and squamous cell carcinoma increased from 7.4% in 2003-2007 to 11.1% in 2008-2012. Patients with small-cell carcinoma had the worst survival (2.9% in 2003-2007 and 3.6% in 2008-2012). The majority of patients with lung cancer are diagnosed with advanced disease. The number of new cases of advanced lung cancer increased from 35.1% to 37.8%. Despite low overall survival, there were positive changes in survival in both sexes, in almost all age groups, and for all histological groups and disease stages. The survival rate of patients with lung cancer in Lithuania is similar to that in other European countries.

Prognostic value of Mastora obstruction score in acute pulmonary embolism.

BACKGROUND: To evaluate the clinical significance of Mastora obstruction score in hemodynamically stable patients with acute pulmonary embolism (aPE). MATERIALS AND METHODS: One-hundred-and-six patients with newly diagnosed aPE, confirmed by computed tomography pulmonary angiography (CTPA), were included in the study and prospectively examined. aPE severity was assessed by using Mastora obstruction score. According to the Mastora index, patients were divided into "non-massive" and "massive" groups. The  patients' medical histories and blood laboratory data were collected, and instrumental tests were performed and analyzed. RESULTS: Eighty-two (77%) of the patients had "non-massive" aPE. Cough (48%), fever (44%), and pleural effusion (48%) occurred significantly more often in the  "non-massive" PE group, while syncope (42%) and right ventricular dysfunction (86%) were more frequent in the  "massive" PE group. The  probability of the  right ventricular dysfunction was significantly higher in the  presence of increased pulmonary artery pressure (Cramer's V = 0.410; p < 0.0001) and respiratory failure (Cramer's V = 0.247; p = 0.032). Increased CRP level was found in the majority of the patients (90%). D-dimer level <500 µg/L (lower than the commonly recommended cut-off level) was found in 5% of cases. CONCLUSIONS: The clinical manifestation depends on the massiveness of aPE. Division of aPE cases into two groups suggests two possible subtypes of aPE: cardiovascular and respiratory. The "non-massive" aPE was associated with respiratory symptoms and an inflammatory response. The  "massive" aPE is associated with an increased D-dimer level and leads to cardiovascular disorders. However, the "massive" aPE may be presented by normal D-dimer concentration level.

Cell-free DNA in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-associated deaths worldwide. Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC). Advances in the knowledge of the biology of non-small cell lung cancer have revealed molecular information used for systemic cancer therapy targeting metastatic disease, with an important impact on patients' overall survival (OS) and quality of life. However, a biopsy of overt metastases is an invasive procedure limited to certain locations and not easily acceptable in the clinic. The analysis of peripheral blood samples of cancer patients represents a new source of cancer-derived material, known as liquid biopsy, and its components (circulating tumour cells (CTCS), circulating free DNA (cfDNA), exosomes, and tumour-educated platelets (TEP)) can be obtained from almost any body fluids. These components have shown to reflect characteristics of the status of both the primary and metastatic diseases, helping the clinicians to move towards a personalized medicine (1). This review focuses on the liquid biopsy component - circulating free DNA, its benefit for non-invasive screening, early diagnosis, prognosis, response to treatment, and real time monitoring of the disease in non-small cell lung cancer patients.