Icotinib Alone Or With Radio Therapy In Patients With EGFR Mutations Non-small Cell Lung Cancer Who Develop Brain Metastases

Objective: Analysis efficiency and prognosis of alone or with radio therapy in patients with EGFR mutations non-small cell lung cancer who develop brain metastases,to determine theoptional managementMethods: A total of 70 patients were enrolled for the study from June 2012 to October 2016 in Fourth Hospital of Hebei Medical University who pathologically diagnosed or cytology for non-small cell lung cancer,with EGFR mutations and had developed brain metastases.All the 70 patients were adenocarcinoma.Exon 18 mutations in 3 cases,exon 19 mutations in 33 cases,exon 21 in 34 cases.Update-GPA grading scale of 1 to 2.5 in 30 cases,40 cases of 3-4.42 patients of 70 were received with icotinib combined radiotherapy,including 7 cases who received systemic chemotherapy.28 patients of 70 received with Icotinib alone,(13 patients were treatde with loca lesion radiotherapy,9 patients were treated with whole brain radiation therapy,20 patients were treated with whole brain radiation therapy and plus dose local).The volume dose of radiotherapy was 30-60 Gy.SPSS22.0 software was applied for survival analysis with Kaplan-Meier method and categorical data with chi-square test.COX model for multiple factors analysis.Logistic method for RR and DCR multi-factor analysis.Results: The intracranial objective response rate(iORR)(iCR+iPR)was 62.9%,the intracranial diseasecontrol rate(iDCR)(iCR+iPR+iSD)was 94.3%.For the group of icotinib alone,intracranial complete remission(iCR)in 4 cases(14.3%),intracranial partial remission(iPR)in 12 cases(42.9%),intracranial disease stability(iSD)in 8 cases(28.6%),and intracranial progressive disease(iPD)in 4 cases(14.3%).Intracranial objective response rate(iORR)(iCR+iPR)was 57.1%,diseasecontrol rate(iDCR)(iCR+iPR+iSD)was85.7%.For the group of icotinib combined radiotherapy,intracranial complete remission(iCR)in 4 cases(9.5%),intracranial partial remission(iPR)in 24 cases(57.1%),intracranial disease stability(iSD)in 14 cases(33.3%).Intracranial objective response rate(iORR)(iCR+iPR)was 66.7%,diseasecontrol rate(iDCR)(iCR+iPR+iSD)was100%.There were no statistical difference for iORR between two groups(?2=0.653,P=0.419),but there were statistical difference for iDCR between two groups(?2=7.698,P=0.022).The median OS of 70 cases were 26.5 months,median PFS were 20 months,median iPFS were 20 months.The 1,2,3 year OS were 89.0%,53.4%,44.8%,nrespectively.The 1,2,3 year PFS were 68.3%,32.6%,24.5%,respectively.The 1,2,3 year iPFS were 72.2%,42.0%,28.0%.The 1,2,3 year OS of the group of icotinib alone were 92.0%,40.9%,24.5%,the 1,2,3 year OS of the group of icotinib combined radiotherapy were 90.0%,57.6%,51.6%,There were no statistical difference between two groups(?2=0.764,P=0.388).The 1,2,3 year PFS of the group of icotinib alone were 70.0%?35.0%?35.0%,the 1,2,3 year PFS of the group of icotinib combined radiotherapy were 67.3%,29.7%,20.8%,There were no statistical difference between two groups(?2=0.460,P=0.497).The 1,2,3 year iPFS of the group of icotinib alone were 73.2%,45.7%,30.0%,the 1,2,3 year iPFS of the group of icotinib combined radiotherapy were 71.8%,40.0%,16.0%,There were no statistical difference between two groups(?2=0.088,P=0.766).Logistic model multi-factor analysis results: the surgery history of pulmonary lesion,Update-GPA grading scale and the number of metastasis organs were OS independent factors,the time to brain metastasis,mutation type and Update-GPA grading scale were PFS independent factors,the time to brain metastasis,mutation type and Update-GPA grading scale were iPFS independent factors.From the therapeutic evaluation of intracranial and the whole,CR were 1 cases,PR were 19 cases,SD were 20 cases,PD were 4 cases,the Kappa value were 0.424.The iDCR of the group of loca lesion radiotherapy,the whole brain radiation therapy and whole brain radiation therapy and local acceleration were 100%,the iORR were 53.8%,77.8%,70.0%,respectively.There were no statistical difference between two groups(?2=1.562?P=0.458).The 1,2,3 year OS?PFS?iPFS of the groups of local lesion radiotherapy,the whole brain radiation therapy and whole brain radiation therapy and local acceleration were 100.0%?90.0%?70.0%,100.0%?44.4%,44.4%,78.7%,45.0%,45.0%;4.6%,33.8%,11.3%,70.0%,20.0%,20.0%,53.0%,33.1%,26.5%;100.0%,50.0%,50.0%;66.7%,22.2%,-%;51.9%,46.2%,46.2%,respectively.There were no statistical difference between two groups(?2=1.473,P=0.479;?2=0.118,P=0.943;?2=3.163,P=0.206).The iDCR of the group of the early involvement of radiotherapy and the sequential group were 100%,the iORR were 77.8%,46.7%,there were statistical difference between two groups(?2=4.200,P=0.040).The 1,2,3 year OS of two groups were 87.9%,53.2%,42.6%;86.2%,64.6%,64.6%(?2=0.235,P=0.628),The 1,2,3 year PFS of two groups were 75.7%,29.4%,24.5%;51.9%,29.6%,14.8%(?2=0.294,P=0.588),The 1,2,3 year iPFS of two groups were 75.3%,42.9%,21.5%;65.5%,36.4%,14.5%(?2=0.005,P=0.941).Conclusion:1 The use of Icotinib to EGFR mutant NSCLC patients with brain metastases have a higher intracranial objective response rate,prolonged survival significantly.2 The history of pulmonary lesion surgery,update-GPA grading scale and the number of metastasis organs were OS independent factors,the time to brain metastasis,mutation type and update-GPA grading scale were PFS and iPFS independent factors.3 The participation of brain radiotherapy can increase iDCR.The early participation of brain radiotherapy can increase iORR.