The Effect And Clinical Analysis Of The Target Therapy On Brain Metastasis Of Driver Genes Positive Non-small Cell Lung Cancer By Cyberknife

Objective: Brain metastases(BMs)are the most common intracranial malignancy in adults and result in a worse prognosis among patients.Based on the available data,radiosurgrey is the currently preferred radiotherapy technique of brain oligo-metastases.The use of targeted therapy has revolutionized the treatment of non small cell lung cancer(NSCLC),which has been the first-line treatment of patients with advanced,recurrent,or metastatic NSCLC harboring driver gene mutations,such as EGFR and ALK fusion gene.Among patients with NSCLC brain metastasis,EGFR mutations or ALK fusion genes were independent prognostic factors of tumor control and predictors of the response of brain metasiss to radiotherapy.However,the impact of targeted theapy on radiosurgery for brain matastasis raised from NSCLC is undetermined and the optimal treatment sequence is not clear.Therefoer we conducted a retrospective analysis to investigate the effect of targeted theapy directed by driver genes in the cyberknife radiosurgery of NSCLC brain metastases.Methods: Between Aug.2006 and May 2018,we reviewed 441 patients with NSCLC who received CKSRS for BM.Our inclusion criteria were as follows: underwent CKSRS treatment,histologically or cytologically confirmed lung adenocarcinoma and an assessed EGFR mutation status or ALK fusion genes,and diagnoses of one or several BMs confirmed by MRI.To avoid potential confounding variables,we excluded patients who underwent surgical resection at the time of initial BM and patients treated with WBRT.Finally,The clinical data of 123 cases of NSCLC with EGFR mutations and 34 cases of NSCLC with ALK-positive was analyzed retrospectively.Overall survival(OS)and intracranial progression-free survival(i PFS)were calculated.The prognostic factors for each group were also determined.Results: For the EGFR mutation group,the median OS for the EGFR-mutant and wild-type groups was 31.0 months(95% CI,15.9 to 46.1)and 19.0 months(95% CI,13.8 to 24.2),respectively,and 27.0 months in the entire cohort(95% CI,21.3 to 32.7).Patients with EGFR mutations who received CKSRS followed by epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)had a longer median OS than did those treated with EGFR-TKI followed by CKSRS(hazard ratio,2.32;95%CI 1.16 to 5.78;P=0.03).On multivariable analysis,EGFR-mutant versus wild-type,limited extracranial metastases were associated with improved OS(P<0.001 and P=0.002,respectively).For the ALK fusion gene positive group,The median PFS of Alectinib group was 24.5 months,and the adverse drug reactions were mild.Conclusion:The current study demonstrated that targeted therapy predicts favorable OS in lung adenocarcinoma patients with 1 to 3 BMs treated with CKSRS.Furthermore,the current findings suggest that CKSRS followed by targeted therapy is associated with favorable OS in patients with driver genes mutant NSCLC who develop brain metastasis.The optimal treatment of lung adenocarcinoma brain metastasis requires personalized and often multidisciplinary therapy.However,prospective,randomized data will be the key solution to these questions.