The Effect Of EGFR Gene On Radiotherapy For Brain Metastases In Lung Adenocarcinoma

Background and ObjectiveThe incidence of brain metastasis in advanced non-small cell lung cancer(NSCLC)is up to 44%,especially in lung adenocarcinoma.The median survival time of untreated patients is 4-11 weeks,while the median survival time of treated patients is 4-15 months.With the further development of lung cancer research into the field of molecular biology,people'understanding of the molecular targets is getting deeper and deeper.Epidermal growth factor receptor(EGFR)is a transmembrane receptor tyrosine kinase,belonging to the ErbB family.Systemically,EGFR signaling is critical for development and adult tissue regeneration.At the cellular level,they are involved in a variety of cellular processes,including cell proliferation,migration,and survival.Functional impairment of the EGFR gene and changes in the EGFR cascade signal are associated with the occurrence of multiple solid tumors in humans,including lung cancer.Multiple studies have shown that EGFR mutation is an important target for the treatment and prognosis of lung adenocarcinoma.EGFR overexpression is associated with tumor cell resistance to chemoradiotherapy,and studies have found that cells harbored EGFR mutation are more sensitive to ionizing radiation,which are associated with cell cycle checkpoint regulation changes,enzyme activity changes,and interference with DNA double-strand mismatch repair.So,for patients with brain metastases from lung adenocarcinoma with different EGFR gene mutations,what is the effect of radiotherapy on intracranial metastasis? The conclusion has not yet been reached.Therefore,we collected the data of 57 patients with brain metastasis from lung adenocarcinoma in the First Affiliated Hospital of Zhengzhou University.The purpose of this study was to investigate the effect of epidermal growth factor receptor(EGFR)gene status on radiotherapy for brain metastases of lung adenocarcinoma,so as to optimize clinical treatment strategy for brain metastasis and provide reference for individualized treatment.MethodsRetrospective analysis was conducted on the clinical data of patients with brain metastasis of lung adenocarcinoma confirmed by pathological biopsy and confirmed by craniocerebral magnetic resonance imaging(MRI)admitted to the First Affiliated Hospital of Zhengzhou University from January 2016 to October 2017.A total of 57 patients were selected as eligible patients.EGFR gene was detected by second-generation sequencing(NGS),probe amplification blocking mutation system(ARMS)or real-time fluorescence quantitative PCR.All patients accepted whole-brain radiotherapy(30 Gy/ 10 F or 40 Gy/ 20F)and local brain lesions boosted by(20 Gy/ 10 F or 40-60 Gy/ 10F),while systemic treatment and primary site control were commonly used in clinical chemotherapy for lung adenocarcinoma.According to the RECIST 1.1 criteria for solid tumor response evaluation,at least one measurable lesion was identified,and the response was assessed by periodic review of CT and MRI.Chi-square Test and Fisher's exact probability method were used to analyze the response rate(RR),Logrank method and Cox-regression model for single-factor and multi-factor analysis.Follow-up was conducted by telephone or case data access.Results1.Patients were followed up for 2 to 21 months,with a median follow-up of 8 months and a quartile interval of 5 months.The response rate of mtEGFR patients to radiotherapy was 79.41%(27/34),and that of wtEGFR was 47.83%(11/23).The mtEGFR group was higher than that of wtEGFR,and the difference was statistically significant(P = 0.013).The response rate of EGFR19 exon deletion mutation group was 80.95%(17/21),and the response rate of 21 exon L858 R deletion mutation group was 76.92%(10/13),with no statistically significant difference(P =1.000).2.Intracranial procession free survival(iPFS)of the mtEGFR and wtEGFR groups was 12.0 and 6.0 months,respectively(P < 0.05).The median iPFS of the EGFR 19 exon deletion mutation subgroup and the EGFR 21 exon L858 R missense mutation subgroup were both 12.0 months,with no statistically significant difference(P > 0.05).3.The number of intracranial metastases and the status of EGFR gene were the influencing factors of iPFS(P = 0.000,0.000).Conclusion1.mtEGFR is more sensitive to radiotherapy for brain metastases in lung adenocarcinoma,which is an independent prognostic factor of iPFS.2.There was no statistically significant difference between the EGFR 19 exon deletion mutant subgroup and the EGFR 21 exon L858 R missense mutant subgroup in RR and iPFS.