Discussion Of Brain Radiotherapy In Patients With EGFR Mutant Lung Adenocarcinoma With Brain Metastasis Treated With EGFR-TKI

Background and Purpose:Lung cancer is one of the most common malignant tumors in China.The frequency of brain metastasis of lung adenocarcinoma is only second to that of small-cell lung cancer.The prognosis of patients with brain metastasis of lung adenocarcinoma is poor,and the natural course of disease is about 3 months.Surgery,stereotactic radiotherapy（SRS）,whole brain radiotherapy（WBRT）and Intensity modulated radiation therapy（IMRT）are important local treatments for patients with brain metastases.For patients with multiple brain metastases,brain radiotherapy and local dosage is added when necessary is the main treatment,which can effectively improve the local control rate of brain metastases and prolong the survival time of patients.However,brain edema and advanced neurocognitive impairment caused by WBRT can lead to the decline of patients’quality of life.Radiation brain injury after brain metastases tumor radiotherapy 1 year cumulative incidence of 8%one 20%^[1],along with the advance of systemic comprehensive treatment for the whole body lesions and to enhance the curative effect of cerebral metastatic lesions,need to evaluate different NSCLC patients with brain metastases,to take a more individualized,precise in patients with different treatments,eventually to cure diseases and prolong survival time and improve the quality of life.The purpose of this study was to use the lung-mol GPA score to explore the best time to use EGFR-TKI to treat patients with Lung cancer with brain radiotherapy in the case of egfr-mutation-positive brain metastasis.Methods:data of 135 patients with brain metastasis of EGFR-mutated lung adenocarcinoma who were admitted to the affiliated cancer hospital of guangxi medical university from January 2012 to August 2019 and received EGFR-TKI treatment after confirming brain metastasis or brain metastasis progression were collected,and the lung-mol GPA score of all patients was calculated.Patients were divided into the EGFR-TKI combined brain radiotherapy group and the EGFR-TKI targeted therapy group according to whether they received radiotherapy for brain metastases at the same time when receiving EGFR-TKI.The main observation indicators were intracranial objective remission rate（iORR）and intracranial disease control rate（iDCR）.Secondary observational indicators survive.Patients who received radiotherapy for brain metastases were subdivided into lung mol GPA 0-2.5 group and lung mol GPA≥2.5 group according to lung mol GPA score.Patients in the two subgroups were divided into the early radiotherapy group（brain radiotherapy was given when brain metastases were found）and the late radiotherapy group（brain radiotherapy was given when brain metastases progressed）according to the timing of brain metastases radiotherapy.Statistical software SPSS21.0 was used for statistical analysis,and COX proportional risk regression model was used to analyze the influencing factors of life duration（OS）and intracranial progression-free survival（i PFS）.Those with statistical significance of single factor analysis were included in multi-factor analysis.Kaplan-Meier method was used for survival analysis,and the difference between curves was tested by Log-Rank method.Patients with P<0.05 were defined as statistically significant,and the difference between the groups was determined by the X²test of the classification variable.Results:1.135 patients had a median survival of 16.62 months and a median intracranial progression-free survival of 14.30months.Single-factor analysis showed that brain radiotherapy,Lung-mol GPA score,number of intracranial lesions,and chemotherapy with pemetrexed plus cisplatin regimen were related to OS.Brain radiotherapy,lung-mol GPA score and ECOG score were correlated with i PFS.Multi-factor analysis showed that brain radiotherapy,Lung-mol GPA score,and chemotherapy with Pemetrexed plus platinum regimen were independent prognostic factors for OS.Multi-factor analysis showed that brain radiotherapy,Lung-mol GPA score and ECOG score were independent prognostic factors for i PFS.2.The median OS of the radiotherapy group and the non-radiotherapy group were 19.22 months and 12.60 months,respectively,with statistically significant differences（p=0.001）.3.The 1-year survival rate of the radiotherapy group was 87.8%,the 2-year survival rate was 75.6%,and the 3-year survival rate was 48.7%.The 1-year survival rate was 79.2%,the 2-year survival rate was 37.7%,and the 3-year survival rate was 33.9%.The 2-year cumulative survival rate in the radiotherapy group was statistically significant（p<0.001）.4.The iORR in the radiotherapy group and the non-radiotherapy group were 52.4%and 28.3%,respectively,with statistically significant differences.The iDCR in the radiotherapy group and the non-radiotherapy group were80.5%and 69.8%,respectively.5.For survival analysis of patients with lung mol GPA score≥2.5 points,the median OS of the early radiotherapy group and the late radiotherapy group were 16.93 months and 25.89 months,respectively,with statistically significant difference（p≤0.001）.Conclusions:1.Brain radiotherapy（p=0.013）,Lung-mol GPA score（p<0.001）,and chemotherapy with pemetrexed plus platinum regimen（p=0.016）were independent prognostic factors for OS.Brain radiotherapy（p=0.010）,Lung-mol GPA score（p<0.001）,and ECOG score（p=0.035）were independent prognostic factors for i PFS.2.Brain radiotherapy for EGFR-TKI treated patients with EGFR-mutated lung adenocarcinoma with brain metastasis can prolong their OS and improve their 2-year survival rate.3.In patients with brain metastasis of EGFR mutant lung adenocarcinoma,ORR and DCR of brain metastasis can be improved when brain radiotherapy is added.4.In patients with lung-mol GPA score≥2.5,when brain metastases are stable,brain radiotherapy intervention can achieve OS extension.