Preliminary Study On Functional Magnetic Resonance Imaging Features Of Brain Metastases From EGFR Mutant NSCLC

The application of EGFR-TKI has become a standard treatment for patients with brain metastases from EGFR mutanted NSCLC.However,studies have found that patients with EGFR sensitive mutations have acquired drug resistance to varying degrees after using EGFR-TKI.Routine craniocerebral magnetic resonance imaging is the preferred method for evaluating the therapeutic effect and drug resistance of brain metastases from EGFR mutated non-small cell lung cancer(NSCLC).With the wide application of functional magnetic resonance(fMRI),quantitative analysis of ADC value can be used to evaluate the grading/staging of tumors and the efficacy of molecular targeted therapy,so that the diagnosis and evaluation of craniocerebral tumors can be expanded from focusing onl y on morphology to focusing on both morphology,cell structure and function.DWI functional magnetic resonance imaging has become a useful supplement to conventional MRI.However,up to now,it is not clear whether the magnetic resonance imaging features,especially functional MRI features of NSCLC patients with brain metastasis are related to the EGFR mutation status.Objectives:1.To investgate the value of the MRI imaging characteristics in assessing the mutation status of EGFR by analyzing the imaging characteristics of brain metastases of NSCLC with different mutation states of EGFR.2.To investigate the value of fMRI in evaluating EGFR mutation in lung adenocarcinoma with brain metastases by measuring the ADC values in patients with lung adenocarcinoma.Methods:1.116 patients diagnosed with brain metastasis from NSCLC in Daping hospital were enrolled during January 2011 to January 2017.MRI imaging data was collected and EGFR mutation status in pulmonary primary tumors or metastasis tissues was detected by amplification refractory mutations system(ARMS).All patients had complete clinic data.The correlation between EGFR mutations and MRI features were retrospectively analyzed,including the number,size,location of the metastatic brain tumors,strengthen approaches,size of peritumoral brain edema of the largest lesion and peritumoral brain edema index.2.55 patients with brain metastasis from lung adenocarcinoma in Daping hospital were enroll during May 2013 to December 2018.MRI imaging data was collected and EGFR mutation status in pulmonary primary tumors or metastasis tissues was detected by amplification refractory mutations system(ARMS).The ADC value in patients with brain metastases from lung adenocarcinoma with different EGFR mutations was analyzed retrospectively.The analysis indexes included tumor ADC value(ADCmax,tADCmin and tADCmean)and relative ADC(rADCmean,rADCmin and rADCmax).Results:1.Among 116 patients with brain metastasis of NSCLC,50 patients with EGFR mutation accounted for 43.1%.EGFR mutationa associated with age(P =0.025),compared with patients abover 60 years of age,19 deletion mutation rate was higher in patients less than or equal to 60 years of age(25.4% VS 10.2%,P = 0.040),but L858 R mutation rate was lower(16.4% VS 34.7%,P = 0.023).Among 203 brain metastases,the peritumoral edema diameters in patients with EGFR wide type and L858 R mutation were significantly higher than that in the 19 deletion mutant group(median: 2.87 VS 1.54,P = 0.008;median:3.31 VS 1.54,P = 0.034,relatively).However,the peritumoral edema index was significantly higher in wild type group than that in 19 deletion mutation group(median: 0.979 VS 0.413,P = 0.012).The predictive model for EGFR 19 deletion mutation was developed based on age,diemeter and index of peripheral edema of metastatic tumor,the capacity of this model was 0.733(95% CI=0.625-0.842)by ROC analysis.2.Among 55 patients with brain metastasis from lung adenocarcinoma,29 patients were EGFR wild type,26 patients were EGFR mutant type,and the mutation rate was 47.3%,with 10 of which in 19 exon deletion mutation and 13 of which in 21 exon point mutation.The tADCmean,tADCmin,rADCmean and rADCmin of intracranial tumors in the EGFR mutation group were higher than those in the wild type group(P = 0.002,0.001,0.001 and 0.012,respectively).After excluding 3cases of the rare mutation types of exons 18 and 20,the analysis among wild type(n=29),19 deletion mutation(n=10)and 21 exon mutation(n=13)showed that the distribution of tADCmean,tADCmin,rADCmean and rADCmin was significantly different among the three groups(P values were 0.006,0.001,0.001 and 0.011,respectively).When compared by pairs other,only 19 deletion mutations were significantly different from wild type in tADCmean,tADCmin,rADCmean and rADCmin values(P = 0.006,0.001,0.001 and 0.008,respectively).Conclusion:1.The clinical and MRI features of NSCLC with brain metastasis are correlated with the mutation status of EGFR gene.2.The ADC value of the brain metastases from lung adenocarcinoma is related to EGFR mutation status.The ADC value of the brain metastatic lesions can indirectly evaluate the biological behavior of BM patients with lung adenocarcinoma in different EGFR mutation states.