| Objective:By comparing and analyzing the genetic testing results of different tissue samples of patients with lung adenocarcinoma with brain(leptomeningeal)metastasis,the differences of genetic testing results among lung adenocarcinoma primary focus,brain metastases,blood and cerebrospinal fluid samples were clarified,and the diagnostic value of genetic testing of samples from different tissue sources for patients with brain metastases was discussed.To provide a theoretical basis for the development of individualized treatment of lung adenocarcinoma with brain(leptomeningeal)metastasis based on accurate gene detection.Materials and methods:In this study,a total of 41 newly diagnosed and rediagnosed patients with brain(leptomeningeal)metastases confirmed by pathology were enrolled in the Department of Neurosurgery and Radiotherapy,Affiliated Hospital of Inner Mongolia Medical University from August 2020 to February 2023,including 27 newly diagnosed patients and 14 rediagnosed patients.There are 36 cases of brain parenchymal metastasis(BPM)and 5 cases of leptomeningeal metastasis(LM).Resection of brain metastases was performed in 8 patients with parenchymal metastases.Patients’ age,gender and other basic data were collected through the electronic medical record system.Collect samples from different sources as the patient’s condition permits and test 16 loci related to non-small cell lung cancer through high-generation sequencing(NGS).Samples collected mainly included samples from primary lung lesions(27 cases),brain metastases(8 cases),blood(41 cases),and cerebrospinal fluid(CSF)samples(13 cases).The blood samples are classified into circulating tumor DNA(ctDNA)samples and circulating tumor cells(CTCs)samples depending on their origin.According to the matching situation of samples and different research purposes,the results of genetic detection of samples from different sources were grouped for comparative analysis.SPSS 25.0 statistical software was used for statistical analysis.Gene mutation rate is defined as the ratio of the number of patients with mutation positive of a gene locus in a specific sample tested to the total number of patients included in the study.Comparison between the count data set Chi-square test or Fisher’s exact probability method,P < 0.05 statistically significant.Results:(1)Among 41 patients with brain(leptomeningeal)metastasis of lung adenocarcinoma,the detection rate of EGFR mutation was the highest at 63.41%,KRAS mutation was 12.20%,ALK mutation was 7.32%,ROS1 mutation was 4.88%,ERBB2 mutation was 2.44%,and the remaining 11 sites were not detected.There was no statistically significant difference in the positive rate of EGFR gene detection among tumor tissue samples(primary lung lesions+brain metastases),blood samples(ctDNA+ CTCs),and cerebrospinal fluid samples((49)>0.05);(2)The detection rates of gene mutations in blood ctDNA and CTCs samples from 41 patients with brain(leptomeningeal)metastasis of lung adenocarcinoma were 82.92% and60.98%,respectively.The positive rate of gene detection in the blood ctDNA sample group was significantly higher than that in the CTCs sample group,with statistical significance((49)<0.05);(3)Among the 27 patients,the positive rate of gene testing for primary lung lesions was85.18%,and the corresponding positive rate of gene testing for blood ctDNA samples was81.48%.The positive rate of gene testing for blood CTCs samples was 51.85%,and there was no statistically significant difference between the three groups((49)>0.05);(4)The genetic test results of 13 patients with brain(leptomeningeal)metastases from lung adenocarcinoma with paired CSF samples showed that CSF samples had the highest rate of positive genes(84.61%);CTCs had the lowest rate of positive genes(30.76%);the rate of positive blood ctDNA genes was between CSF samples and CTCs samples(38.46%),and the comparison of the three was statistically significant(P < 0.05);two of the positive CSF samples showed rare EGFR mutations,namely EGFR exon20 T790 M mutation and EGFR exon20 insertion mutation,while their corresponding blood samples were negative.Gene testing of previous lung primary lesion samples from individuals with EGFR T790 M mutation suggests EGFR L858 R mutation and prior oral treatment with gefitinib;(5)Mutations were detected in 5(83.30%)of the 6 patients with primary lung foci,4(66.70%)of their paired cerebrospinal fluid samples and 5(83.30%)of their paired blood ctDNA samples,with no statistically significant comparison between the three groups(P>0.05);(6)Among the 8 patients with BPM,the gene detection rate of CSF samples was 87.50%;among the 5 patients with LM,the gene detection rate of CSF samples was 80.00%,and the difference between them was not statistically significant(P>0.05);(7)The positive rate of gene testing in the tissue samples of brain metastases from 8patients with BPM lesions who underwent surgical resection was 87.50%,while the positive rate of gene testing in paired CSF samples was 75.00%,and the positive rate of gene testing in blood ctDNA samples was 12.50%.There was a statistically significant difference in the positive rate of gene testing between brain metastases and CSF samples(P <0.05),However,there was a statistically significant difference in the positive rate of gene testing between blood ctDNA samples,brain metastasis samples,and CSF samples(P <0.05).Conclusion:(1)The detection rate of EGFR gene mutations is highest among different tissue samples in gene testing results,and tissue samples,blood samples,and cerebrospinal fluid samples can all be used as reliable samples for EGFR gene testing;(2)The positive rate of blood ctDNA gene testing is higher than that of CTCs samples.For those who can only obtain blood samples for gene testing,blood ctDNA is the preferred testing sample;(3)The positive rate of gene testing for primary lung lesions is no different from that of blood samples.For those who cannot obtain primary lung lesion samples,blood is also a reliable substitute sample;(4)The positive rate of gene testing in CSF samples is higher than that in blood samples,and CSF may detect rare mutation sites and reveal the reasons for tumor resistance or brain(membrane)metastasis;(5)The positive rates of gene detection in primary lung lesions and CSF samples are higher than those in blood samples,but CSF samples can better reflect the true molecular characteristics of brain metastases;(6)Both BPM and LM patients have higher positive rates for genetic testing in CSF samples.Regardless of the sample collection conditions,both BPM and LM patients prefer CSF samples for genetic testing;(7)CSF samples and brain metastasis samples have high positive rates for gene testing.CSF can be a reliable sample selection for patients who cannot obtain brain metastasis samples,and CSF may be a potential alternative sample for brain metastasis samples.There are varying degrees of differences in gene testing results between lung primary lesion samples,brain metastases samples,blood samples,and cerebrospinal fluid samples.Timely selection of multiple samples,including cerebrospinal fluid samples,for gene testing during the treatment process of lung adenocarcinoma patients with brain(leptomeningeal)metastases is of great significance for the development of accurate diagnosis and treatment plans. |
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