Clinicoradiologic Features Associated With EGFR And ALK Gene Mutation In Lung Adenocarcinoma

Purpose1.To retrospectively identify clinicopathologic and radiological characteristics that could be independent predictors of epidermal growth factor receptor exon 19 and 21 mutation and ALK rearrangement in surgically resected lung adenocarcinomas in a cohort of Asian patients,Searching for independent predictors of corresponding gene mutations and building models;2.To compare the demographic,histopathological and radiological characteristics between EGFR mutation and ALK rearrangement-positive tumors in order to better differentiate the two gene mutations.Materials and methods The study population was retrospectively selected from patients who underwent surgical resection and histologically confirmed lung adenocarcinoma in our hospital between October 2015 and January 2017.A total of 505 patients were included according to the inclusion criteria and subsequently used to analyze for any associations between demographics,histopathology data and preoperative chest computed tomography with EGFR mutation status and ALK rearrangement.A total of 24 CT descriptors were assessed.All statistical analyses were performed using Medcalc 15.6.1 and SPSS 19.0.Univariate analysis was used to assess the association between clinicoradiologic features with gene mutation status.Non-parametric two-sample Wilcoxon test was used for the order variables and continuous variables,and chi-square test or Fisher’s test for categorical variables.Subsequently,multivariate analysis was performed to calculate the odds ratios with95% CI through a logistic regression model with backward stepwise selection of variables.ROC curves were drawn according to their significant characteristics,and the corresponding AUC value was calculated.P-values < 0.05 were considered statistically significant.Results1.EGFR mutations were existed in 252(53.5%)of 471 patients,and associated with11 clinicoradiologic features.For the model with both clinical and radiological features,the independent predictors of harboring EGFR mutation were small maximum diameter(≤ 3.9cm)(P=0.020),non-smokers(P<0.001),micropapillary pattern(P=0.034),pleural retraction(P=0.044),vascular convergence(P<0.001)and absence of solid pattern(P=0.045).The area under the receiver operating characteristic curve was 0.784.2.Multivariable logistic regression analysis indicated that non-smokers(P<0.001),vascular convergence(P<0.001)and absence of solid pattern(P=0.045)were important independent predictors of EGFR exon 19 mutation,while non-smokers(P<0.001)and vascular convergence(P<0.001)were independent predictors of EGFR exon 21 mutation.The area under the ROC curve was 0.807 and 0.794,respectively.Lepidic growth pattern appeared more frequently in exon 21 mutant tumors than in exon 19 mutant group(p< 0.001).3.ALK rearrangement were existed in 39(7.7%)of 505 patients,and associated with 13 clinicoradiologic features.For the model with both clinical and radiological features,the independent predictors of harboring ALK rearrangement were younger patients(P=0.010)、infiltrating mucous component(P<0.001)and absence of pleural retraction(P=0.009).The area under the receiver operating characteristic curve was 0.877.4.Younger patients(P = 0.010),stage II and III tumors,solid pattern(P = 0.002)and infiltrating mucus type(P < 0.001),lobulation sign(P = 0.002),solid texture(P< 0.001)and liquefaction necrosis(P = 0.001)were more frequent in ALK rearrangement positive tumors;while stage I tumors,acinar pattern(P = 0.011)and lepidic pattern(P < 0.001),pleural retraction(P < 0.001),vascular convergence(P=0.002),spiculation(P=0.004),GGO component(P<0.001),bubblelike lucency(P=0.013)and nodules in nontumor lobes(P=0.003)were more common in EGFR mutation tumors.Conclusion CT imaging features of lung adenocarcinomas in combination with clinical variables could be used to prognosticate EGFR mutation status and ALK rearrangement,the separate analysis of EGFR exon 19 or 21 mutation could further improve diagnostic performance.