CT features of mutated non-small lung carcinoma of the lung: Comparison with non-mutated non-small lung carcinoma

Lung cancer is one of the leading causes of death worldwide. Adenocarcinoma is the most common histologic subtype of lung cancer. Over the past decade, molecular-targeted therapies have led to a research era on accurate analyses of biomolecular markers (EGFR, ALK and ROS 1) in a subset of lung adenocarcinomas. Epidemiologic studies show that nonsmoking status and female sex were described as predictors of EGFR mutation that enable efficient plans for earlier diagnosis and treatment. The new classification system of lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) highlights the importance of radiological-pathological correlation studies to predict histopathological subtypes and patient prognosis Many studies showed that EGFR-mutated adenocarcinoma tends to develop diffuse and random pulmonary metastases compared with the wild type (Non-mutated ) and also many have reported that non–small cell lung cancer (NSCLC) with ALK rearrangement was associated with CT scan characteristics of central tumor location, absence of pleural tail, and large pleural effusion. If CT imaging correlates of clinically relevant gene expression signatures, such as EGFR, ALK, and ROS1, were established in NSCLC, this could be cost-effective, help redefine existing staging and early treatment. In this retrospective study, our purpose was analyze to computed tomography (CT) features of non-small cell lung carcinoma on the basis of epidermal growth factor receptor gene (EGFR), Anaplastic lymphoma kinase gene (ALK) and c-ros oncogene 1 (ROS1) rearrangement mutation status. Methods and Materials This retrospective study was approved by our institutional review board (Dokuz Eylul University Hospital) and informed consent was waived Patient Selection Consecutive patients (median age 63.08 years, range 28–89 years, N = 155 [104 men and 51 women]) who had pathologically confirmed diagnoses of primary lung adenocarcinoma at Dokuz Eylul University Hospital between January 2013 and June 2018 were investigated retrospectively in this study. Inclusion criteria determined as a pre-treatment chest CT study of a primary tumor at our institution, a cell type diagnosis of adenocarcinoma, and data on EGFR and/or ALK and/or ROS-1 rearrangement status. Exclusion criteria consisted of a CT performed at another institution. Analysis of EGFR, ALK, ROS1 Status All patients were evaluated for EGFR, ALK and ROS 1 mutation status using histologic or cytologic specimens by nucleic acid polymerase chain reaction and by fluorescence in situ hybridization (FISH). CT image acquisition and interpretation The CT images independently and blindly analyzed by one radiologist with 4 years' experience. Evaluation of CT images was done on a mediastinal window (M, 20–40; W, 300) and lung window (M, –500 to–700; W, 1500–2000) using Digital Imaging and Communications in Medicine (DICOM) images. For each patient, age, sex, the presence of distant metastases, and smoking status (positive for current or former smoking for at least 10 years) were extracted from the medical records. The CT findings were retrospectively analyzed for tumor size (as the three diameter of the tumour on axial and coronal images ) , presence or absence distant metastases, presence or absence surrounding ground-glass opacity, mediastinal lymph node (Any lymph node with a short-axis diameter ≥1 cm is considered to be abnormal ), vascular invasion ( which was determined on CT as thickening of the vascular bundle or to have close contiguity to vascular bundle ), presence or absence of calcification, presence or absence central necrosis, pleural indentation (presence or absence of pleural contact ), margins ( indicated as smooth or spiculated/irregular ) cavity ( presence of round or oval air density in the tumor with a relatively thick wall ), and presence or absence pleural effusion. Statistical Analysis Clinical and pathological findings including age, sex , smoking history, pathological findings, CT features were compared using the chi-square test, the unpaired t-test or Fisher's exact test, as appropriate. Also, the study population was expressed as medians (ranges) for nonparametric variables. To detect the abnormal distribution of database Kolmogorov-Smirnov test added to analyze. A p-value <0.05 was considered significant. All statistical analyses were performed using the SPSS, version 15. RESULTS Clinical Characteristics of the Study Population The clinical characteristics of 155 patients included in the study are shown in Table 1. median age of study group was 63,4±0.8 years (range 28–89 years); 104 were men and 51 were women. Median ages of mutated group (EGFR, ALK and ROS1) and non-mutated group were 64.0±1.1 and 62.9±1.0 respetively with no significant difference (p=0.454). The percentage of smokers in 155 patients was 61.9 % (n=96). 51.9% in the mutated group and 71.8% in the non-mutated group. Gene mutations ( EGFR, ALK,ROS 1 ) were significantly more frequent in women (74.5 %) than in men (37.5 %) (p<0.01) Our study shows; in mutated group ( EGFR, ALK, ROS 1 ) women and non-smokers were significantly higher compared within the non-mutated group. Imaging Features Imaging features of the NSLC according to mutation status are shown in Table 2. Between mutated and non-mutated group, there were no significant differences in tumor size, vascular invasion, central necrosis, pleural effusion, distant metastasis, mediastinal lymph node, the presence of cavity and ground glass opacity. The only difference was found in calcification which was significantly higher in non-mutated tumors (10.3 %, n=8) than in mutated tumors (1.3 %, n=1) (p=0.034). According to EGFR Status Testing for EGFR mutation was positive in 62 patients ( 40% ) who had a median age of 64.3±1.2 years and also ALK mutation was positive in 9 patients, ROS 1 was positive in 6 patients (3.9%). No significant differences were shown. But the frequency of woman was significantly higher in EGFR mutated group than in non-EGFR mutated group. (50.0 % , n=31; 21.5% n= 24 respectively )(p<0.01,) Overall, the frequency of smokers was significantly higher in the nonmutated group than in the EGFR mutated group. (p=0.012 ) Also, there were significant differences in distant metastasis and mediastinal lymph node metastasis between EGFR mutated group and non-EGFR mutated group. (p=0.048, p=0.041, respectively) Among in 155 patients, within two groups (EGFR -mutated and Non-EGFR mutated ), there was no significant difference in the vascular invasion, central necrosis, pleural effusion, presence of cavity and ground glass opacity. Conclusion CT-based radiogenomic features of non-small lung carcinomas can give useful information regarding tumor phenotype. Our study shows; in mutated group (EGFR, ALK, ROS 1) women and non-smokers were significantly higher compared within the non-mutated group. Also, there were significant differences in distant metastasis and mediastinal lymph node metastasis between EGFR mutated group and non-EGFR mutated group. (p=0.048, p=0.041, respectively)