The Optimal Pattern Of Intracranial Radiotherapy Combined With TKI For Brain Metastases Of Adenocarcinoma Patients

ObjectiveRadiotherapy(RT)and epidermal growth factor receptor tyrosine kinase inhibitors(TKIs)are conventional treatments for brain metastases from EGFR mutant non-small cell lung cancer(NSCLC).This multicenter regression analysis aims to propose an optimal treatment plan for patients with brain metastases from EGFR mutant lung adenocarcinoma.Materials and methodsA total of 153 cases of brain metastases from lung adenocarcinoma were included in this study.The samples were collected from inpatients received by 13 medical units in Zhejiang Province from January 1,2013 to June 30,2018.This study retrospectively collected the basic characteristics of each case and the treatment methods experienced during the course of the disease,as well as time and dose information,then compared the differences in radiosensitivity of brain metastasis between the EGFR mutant group and the EGFR wild-type group.Intracranial progression-free survival after radiotherapy(i PFS-RT)、 survival after radiotherapy(OS-RT)and overall survival(OS)statistical analysis was performed.The impact of different treatment factors on the overall survival of patients were also analyzed.The chi-square test was used to compare the local control rate(DCR)and objective response rate(ORR).The Kaplan-Meier method was used to compare intracranial progression-free survival(i PFS-RT)、survival after radiotherapy(OS-RT)and overall Survival(OS).The log-rank test was performed for univariate analysis,the Cox proportional hazard model was used for multivariate analysis.ResultsAssessment of intracranial control after brain metastasis radiotherapy: the EGFR mutant TKI-naive group was the best,and the intracranial control rate in the TKIresistance group was significantly slacked(ORR:73.1% vs 20.0%,p=0.003);Compared with the EGFR wild-type group,the TKI-naive group had a significant advantage(ORR:73.1% vs.38.5%,p=0.004),while the TKI-resistance group had no advantage compared with the EGFR wild-type group(ORR: 20.0% vs.38.5%,p=0.511).In EGFR-mutant patients with brain metastasis,the TKI-na?ve group had longer i PFS-RT and OS-RT than the TKI-resistance group(median i PFS-RT:20.3 vs 5.7 months,p=0.001;Median OS-RT:24.3 vs 11.0 months,p=0.002).There was 4.9 months difference in OS between the two groups(median OS:24.3 vs 19.4 months,p=0.963).While in the subgroup analysis,patients with features of multiple brain metastases(>3)and metastases-related symptoms had a longer OS in the TKI-na?ve group than those in the TKI-resistance group(median OS: 26.7 vs 15.6 months,p = 0.014).The survival of patients with peritumor edema(Median OS: 22.7 vs.16.7 months,p = 0.155)or with multiple brain metastatic lesions(> 3)(22.7 vs 15.5 months,p = 0.132)at initial diagnosis in the TKI-na?ve group has a tendency to prolong,compared with those in the TKI-resistance group.And patients with 2-3 ECOG-PS scores had a higher risk of 2.408 times in overall survival than patients who scored 0-1(HR=2.408,95%CI:1.246-4.655,p=0.009).ConclusionEGFR mutant brain metastases in adenocarcinoma lung cancer patients,which are na?ve to TKIs,have higher radiosensitivity,then followed by patients with EGFR wild-type brain metastases,and brain metastases after TKI resistance have the lowest sensitivity to radiation.The combination of radiotherapy and TKI extended the intracranial control time in patients with EGFR-sensitive mutant brain metastases.Patients with radiation therapy combined with TKI have a longer median survival time than patients received salvage radiotherapy after resistance to TKI,especially those with more metastases、brain metastasis-related symptoms and Peritumoral edema.