Clinical Prognostic Analysis Of Patients With Brain Metastases In Non-Small Cell Lung Cancer With Driver Sensitive Mutation

Purpose: The aim of this study was to analyse the prognostic factors in BMs(brain metastasis)patients with driver mutation.The study also aims to compare the survival effects of TKI(tyrosine kinase inhibitors)alone and in combination with brain radiotherapy in NSCLC-BMs(non-small cell lung cancer brain metastasis)patients with EGFR(epidermal growth factor receptor)-sensitive mutations.In addition,the timing and protocols of brain radiotherapy interventions were explored,in order to develop individualized treatment plans to delay disease progression and even improve patient survival.Methods: We retrospectively analyzed the survival and clinical features of 189 patients with NSCLC-BMs with driver-sensitive mutations,and performed univariate and multivariate analysis of the prognostic factors related to BMs.115 patients with EGFR sensitive mutation were selected and divided into TKI combined radiotherapy group and TKI treatment group according to the treatment plan.The efficacy of the two groups was compared.Then cases of TKI combined radiotherapy group were divided into early radiotherapy group and late radiotherapy group to compare the efficacy of the two groups.Comparisons between groups were made using the x2 test or Fisher’s exact probability method.Kaplan-Meier method was used to compare i PFS(intracranial progression-free survival)and OS(overall survival time)among groups.Results:1.Median OS,median i PFS of 189 patients with NSCLC brain metastasis were 24 months(1-68 months)and 14 months(1-66 months),respectively.Median OS and i PFS were 24months(1-68 months)and 14 months(1-66 months)in patients with EGFR-sensitive mutations,and 22 months(4-58 months)and 12 months(2-56 months)in patients with ALK fusion mutations.2.The results of OS univariate analysis showed that the age of brain metastasis at diagnosis,KPS score,symptoms of brain metastasis,status of extracranial metastasis and Lung-mol GPA score were related factors of post-BMs OS.Multivariate COX regression analysis showed that age,symptoms of brain metastasis,and Lung-mol GPA score were independent prognostic factors for OS.Univariate analysis of i PFS showed that KPS score,Lung-mol GPA score and treatment plan were related factors affecting i PFS.Multivariate analysis showed that treatment plan were independent prognostic factors of i PFS.3.Patients aged < 60 years at the time of diagnosis of BMs had a significantly longer median OS than those aged ≥60 years(27 vs.20 months,P=0.001).Patients with symptomatic BMs had a poorer prognosis,with a median OS of 9 months shorter than those with asymptomatic BMs(20 vs.29 months,P=0.020).Patients with a Lung-mol GPA < 3 had a median OS of 18 months and those with a Lung-mol GPA ≥3 had a median OS of 30 months(P < 0.001).4.Patients with extracranial metastases before diagnosis of BMs had poorer survival than those without BMs(m OS: 21 vs.27 months,P=0.018).Among extracranial metastases,patients with liver metastases had the worst prognosis(m OS: 14 vs.25 months,P=0.001).5.The median OS of long-surviving BM patients(≥36 months)was 53 months.Patients with NSCLC BMs with driver gene mutations who younger than 60 years old(P= 0.010),had undergone surgery for brain metastases(P=0.029),had no extracranial metastases(P=0.033),Lung-mol GPA score ≥3(P < 0.001)were more likely to survive long term.6.In patients with EGFR-sensitive mutated BMs,TKI combined with radiotherapy extended i PFS(33 vs.17 months,P=0.003),but no significant benefit was seen in OS(36vs.29 months,P=0.535).TKI combined with radiotherapy had a significant advantage over TKI treatment in patients with symptomatic brain metastases(mi PFS: 36 vs.16 months,P=0.001;m OS: 38 vs.18 months,P=0.004).In patients with TKI combined radiotherapy,the median i PFS in the early radiotherapy group had a longer trend than that in the late radiotherapy group but There was no significant difference(24 vs.16 months,P=0.084).There was also no significant difference in OS between the early and late radiotherapy groups(26 vs.25 months,P=0.519).7.Patients with NSCLC meningeal metastases have a poor prognosis despite with driver sensitive mutations.Their median OS was 13 months(9-16 months).There was no survival benefit from TKI combined with radiotherapy(13 vs.12 months,P=0.314).Conclusions:1.NSCLC-BMs patients with driver sensitive mutation who were less than 60 years old,asymptoms of brain metastasis and Lung-mol GPA score ≥3 had a better prognosis.Patients with extracranial metastases prior to brain metastases had poorer survival,especially in patients with liver metastasis.2.Compared with TKI therapy,TKI combined with radiotherapy can significantly benefit i PFS in patients with EGFR-sensitive mutations in NSCLC-BMs,and significantly prolong OS in who have symptomatic BMs.Early radiotherapy may be advantageous in patients treated with TKI combined with radiotherapy.