Association Between CT Features Andgene Mutations In Patients With Singleor Multiple Primary Lung Adenocarcinomas

Part Ⅰ Association Between CT Characteristics with EGFR Mutations and Positive ALK Expression in Patients with Lung Adenocarcinoma: A Retrospective Analysis of 827 CasesObjectives: The aim of this retrospective study was to identify the relationships of epidermal growth factor receptor(EGFR)mutations and anaplastic large-cell lymphoma kinase(ALK)status with CT characteristics in adenocarcinoma.Methods: Preoperative chest CT findings were retrospectively evaluated in 827 surgically resected lung adenocarcinomas in our institution from 2010 January to2017 December.All patients were tested for EGFR mutations and ALK status and underwent chest CT prior to treatment.According to the EGFR mutation,they were divided into effective mutation group(489 cases)and non-effective mutation group(338 cases).According to ALK rearrangement status,they were divided into ALK-positive group(57 cases)and ALK-negative group(770 cases).The independent-sample Student’s t test was used to compare two groups of normally distributed variables(age and tumor size),and the chi-square test was used to compare categorical variables(other clinical features and CT signs).Logistic regression analyses were performed to identify independent factors of predicting EGFR and ALK mutations.Receiver operating characteristic(ROC)curves were constructed for the combined independent factors for predicting EGFR mutant or ALK positive.Results: EGFR effective mutations were found in 489(59.1%)patients,and ALK positive were found in 57(7.0%)patients.EGFR effective mutations was more common in females(p<0.001),those who had never smoked(p<0.001),tumors with lepidic predominant subtypes(p<0.001)and less lymph node metastasis(p=0.006),smaller tumors(p<0.001),peripheral lesions(p=0.035),tumors that presented with ground-glass opacity(GGO)(p<0.001),especially in mix GGO(p=0.045),air bronchograms(p < 0.001),pleural retraction(p<0.001),a well-defined margin(p=0.022)and those without lymphadenopathy(p=0.001).The most significant independent prognostic factors of EGFR effective mutations were tumors with female(OR=1.713,95% CI:1.117,2.628),non-smoking status(OR=0.557,95% CI:0.357,0.868),GGO(OR=3.035,95% CI : 1.841,5.004,air bronchograms(OR=2.895,95% CI:1.336,2.737)and pleural retraction(OR=12.055,95% CI:1.557,3.061)by logistic regression analyses.The receiver operating characteristic(ROC)curve yielded area under the curve(AUC)values of 0.682 and 0.758 for clinical only or combine CT features,respectively,for the prediction of EGFR mutations,and significant difference was found between them(p <0.0001).ALK positive status was found more frequently in younger patients(p<0.001),tumors with solid predominant subtypes or mucinous lung adenocarcinoma.In CT,solid tumors(p=0.009)and lesions without air bronchograms(p<0.001)and distant metastasis(p<0.001)were associated with ALK positive.Logistic regression analyses showed the most significant independent prognostic factors of ALK positive were age(OR=0.940,95%CI: 0.910,0.972),tumors with solid predominant subtypes or mucinous lung adenocarcinoma(OR=7.994,95% CI: 4.183,15.278),presented as solid tumors(OR=0.292,95% CI: 0.097,0.878)and lesions without air bronchograms(OR=0.307,95% CI: 0.123,0.767)in CT.ROC curve analysis showed that use of clinical variables combined with CT features(AUC = 0.739)was superior to use of clinical variables alone(AUC = 0.657)for the prediction of ALK positive,and significant difference was found between them(p <0.0001).Conclusion: GGO appearances,air bronchogram and pleural retraction were noted as the predominant imaging characteristics of EGFR mutation tumors.In contrast,tumor with ALK positive were characterized by solid nodules without air bronchogram but with distant metastasis on CT.Part Ⅱ CT Features Associated with EGFR Mutations and ALK Positive in Patients with Multiple Primary Lung AdenocarcinomasObjectives: The aim of this retrospective study was to identify the relationships of epidermal growth factor receptor(EGFR)mutations,anaplastic lymphoma kinase(ALK)status with CT characteristics in multiple primary lung adenocarcinomas(MPLAs)patients.Materials and Methods: Patients with MPLAs were selected from our institution,Criteria for the definitions MPLAs closely adhered to the Martini and Melamed classification.All 67 patients(135 lesions)were tested for EGFR mutations and ALK status and underwent chest CT prior to any treatment.The independent-sample Student’s t test was used to compare two groups of normally distributed variables,(age and tumor size),and the chi-square test was used to compare categorical variables(other clinical features and CT signs).Logistic regression analyses were performed to identify independent factors of predicting EGFR and ALK mutations.Receiver operating characteristic(ROC)curves were constructed for the combined independent factors for predicting mutant EGFR or ALK.Results: Among MPLAs patients,EGFR effective mutant was more common in females(p=0.002)and those who had never smoked(p=0.010),and the tumors presented as ground-glass opacity(GGO)(p=0.003)and air bronchograms(p=0.012). Logistics regression analysis showed that,GGO(OR=6.550,p=0.010)correlation with EGFR effective mutations,and air bronchograms was not in correlation with EGFR effective mutations(OR=3.527,p=0.060).The receiver operating characteristic(ROC)curve yielded area under the curve(AUC)values of 0.647 and 0.712 for clinical only or combine CT features,respectively,for the prediction of EGFR mutations in MPLAs,and significant difference was found between them(p =0.0334).ALK positive status was found more frequently in MPLAs patients who were younger(p=0.002)and had never smoked(p=0.010).ALK positive status was associated with solid tumors in both the MPLA(p<0.004)in CT scan.Logistics regression analysis showed that solid nodules(OR = 6.550,p = 0.010)was an independent factor predicting ALK positive in MPLAs.The ROC curve yielded AUC values of 0.767 and0.804 for clinical only or combine CT features,respectively,for the prediction of EGFR mutations in MPLAs,but no significant difference was found between them(p=0.2267).Conclusion: Non-smoking women,presented as GGO and air bronchograms on CT are more susceptible to have EGFR mutations.Non-smoking,young patients with solid lesion on CT had a high ALK positive rate in MPLAs.