The Treatment Of EGFR-TKIs For Brain Metastases Of Nsclc

BackgroundIn recent years,the morbidity and mortality of lung cancer is increasing year by year,it has became one of the biggest threat of the malignant tumor to human health and life.Brain metastases of lung cancer is one of the leading causes of death in patients with lung cancer.Due to the presence of the blood-brain barrier,the effect of chemotherapy drugs for the treatment of cerebral metastases is limited.At present,the brain radiotherapy is still the standard treatment for patients with brain metastases of lung cancer.Numerous studies have confirmed that the wide use of targeted drugs to patients that EGFR is positive has greatly improved the prognosis of patients with non-small cell lung cancer.Meanwhile,it also opens up a new direction for the treatment to patients with brain metastases.The sequence of the application of targeted drugs and brain radiotherapy still needs further research.ObjectivesThe objectives of this study is to explore how the different treatment influence patients' pronosis respectively,which consists TKIs alone?TKIs combined with craniocerebral radiotherapy and chemotherapy combined with radiotherapy.Thus,we can summarize the relationship between the different treatment of patients with non-small cell lung cancer and brain metastases with their intracranial and extracranial progression-free survival.In the future,it can provide reference for the choice of treatment.MethodsUsing the real world study,we retrospectively analyzed patients with non-small lung cancer and brain metastasis in the Qilu Hospital of Shandong University from January 2010 to December 2016.They were all confirmed BM by pathological diagnosis.We collected patients's information of gender,age,smoking history,the time of brain metastases,brain metastasis symptoms,PS scores,the number and location of brain metastasis,EGFR mutations status,and the treatment.According to the treatment of the patients,we devided the patients in three groups(EGFR TKI alone.TKIs combined with craniocerebral radiotherapy and chemotherapy combined with craniocerebral radiation).The primary end point is intracranial progression-free survival(iPFS),systemic PFS and overall survial(OS).The second end points is disease control rate(DCR).the objective response rate(ORR)and adverse reactions.Results1.There are 112 patients recorded in total.The group treated by TKIs combined with craninocerebral radiotherapy contains 33 patients.The group treated by TKIs contains 26 patients.While,The number of patients treated by chemotherapy combined with craniocerebral radiotherapy is 53.The number of cases that EGFR mutant is 59 cases.Among them,30 had brain metastases at the initial diagnosis.2.No significant differences were observed between the EGFR TKI alone group and the TKIs combined with craniocerebral radiotherapy group regarding intracranial PFS(6.6 vs 7.8 months,p=0.167)or systemic PFS(7.7 vs 9.7months,p=0.146).The patients treated by TKI combined with craniocerebral radiotherapy had longer overall survial(OS)than patients treated by TKIs(21.0 vs 12.0 months,p=0.011).3.The outcome of patients treated by chemotherapy combined with craniocerebral radiotherapy:CR 1,PR 32,SD 17,PD 3,ORR 62.26%,DCR 94.34%.4.No significant differences were observed in three groups regarding erythra(P>0.05),but there were differences regarding hepatic function damage?reduction of white cell?the reduction of thrombocyte and radiation-induced brain injuries above grade 3(P<0.001).Patients treated by chemotherapy combined with craniocerebral radiotherapy had the higher incidence of reduction of white cell and the reduction of thrombocyte above grade 3 than patients treated by TKIs combined with craniocerebral radiotherapy(P<0.001).The incidence of radiation-induced brain injuries above grade 3 caused by TKI combined with craniocerebral radiotherapy is higher than it caused by chemotherapy combined with craniocerebral radiotherapy,especially in delayed radiation-induced brain injuries.ConclusionsThere is no significant differences between patients with EGFR mutant treated by TKIs conbined with radiation therapy compared with patients treated by TKIs regarding iPFS and sPFS.But the additional radiotherapy could improve OS in EGFR mutant NSCLC patients.Patients with EGFR negative and brain metastases can get satisfactory disease control rate or the objective response rate treated by chemotherapy combined with craniocerebral radiotherapy.Patients treated by chemotherapy combined with craniocerebral radiotherapy have the higher incidence of reduction of white cell and the reduction of thrombocyte above grade 3 than patients treated by TKIs combined with craniocerebral radiotherapy.The incidence of radiation-induced brain injuries above grade 3 caused by TKI combined with craniocerebral radiotherapy is higher than it caused by chemotherapy combined with craniocerebral radiotherapy,especially in delayed radiation-induced brain injuries.