Intracranial Control And Survival Outcome Of Whole Brain Radiotherapy(WBRT) Alone Versus WBRT Plus Radiotherapy Boost For Non-small Cell Lung Cancer With Brain Metastases

Objectives:To compare the difference in survival and intracranial local control between patients with whole brain radiotherapy(WBRT)and WBRT plus external beam radiotherapy boost(RTB)in non-small cell lung cancer(NSCLC)patients with brain metastases(BMs),and explore the prognostic factors for BMs patients with brain radiotherapy.Methods:206 patients diagnosed with NSCLC with BMs between May 2010 and October 2017 in the Third Affiliated Hospital of Kunming Medical University(Yunnan cancer hospital)were retrospectively reviewed.Of these patients,140 patients underwent WBRT alone(WBRT alone group),and another 66 patients underwent WBRT plus RTB(WBRT plus RTB group).Patient baseline characteristics included gender,age,smoking status,KPS score,pathological type,targeted therapy,chemotherapy,extracranial metastases,location and size of BMs,neurological symptoms,GPA score,RPA grade,ways of cranial radiotherapy,dose and regimen of WBRT and so on.The endpoints included intracranial local progression-free survival and regional progression-free survival time(iLPFS and iRPFS,respectively)and overall survival(OS).Survival curves were generated using the Kaplan-Meier method and compared using the log-rank test.The log-rank test was also used for univariate analyses of prognostic factors.The variables with p-values of less than 0.1 from univariate analyses were further analyzed in the multivariate analyses using the Cox proportional hazards regression model to assess prognostic factors related to OS,iLPFS and iRPFS.Results:The median follow-up time was 22.7 months.The median OS,iLPFS and iRPFS of all patients were 25.8 months,19.3 months and 17.2 months,respectively.The median OS in the WBRT alone group was 25.8 months,and the median OS in the WBRT plus RTB group was 37.6 months.The 6-,12-,and 24-month OS rates in the WBRT alone group were 95.0%,75.6%,54.9%,and 97.0%,86.9%,56.4%in the WBRT plus RTB group,respectively(p=0.200).The median iLPFS was 17.9 months in the WBRT alone group and 22.3 months in the WBRT plus RTB group.The 2-year iLPFS rates were significantly lower in the WBRT alone group than in the WBRT plus RTB group(34.5%vs.49.3%,p=0.041).The median iRPFS was 17.9 months in the WBRT alone group and 15.3 months in the WBRT plus RTB group.The 2-year iRPFS ratewas not significantly different between the two groups(38.4%for the WBRT alone group and 27.3%for the WBRT plus RTB group,p=0.347).The multivariate analysis found that RPA class 1(p=0.041),without smoking history(p=0.038),good GPA score(p=0.039)and treatment with EGFR-TKIs therapy(p<0.001)were independent factors associated with better OS;treatment with EGFR-TKIs therapy(p=0.001),RPA class 1(p=0.034),and good GPA scores(p=0.002)were signifcantly associated with better iLPFS;no chemotherapy during brain radiotherapy(p=0.002),few brain lesions(p=0.025),treatment with EGFR-TKIs therapy(p<0.001),and good GPA scores(p=0.025)were independent favorable risk factors for iRPFS.From the results of univariate and multivariate analyses,we concluded that treatment with EGFR-TKIs therapy was an independent prognostic factor associated with OS,iLPFS,and iRPFS.Therefore,we further performed a subgroup analysis of patients treated with EGFR-TKIs therapy to explore the survival and intracranial local control differences between the two treatment groups.In patients with EGFR mutation andEGFR-TKIs therapy(n=62),the median OS,iLPFS and iRPFS was 58.3 months,24.7 months and 20.2 months,respectively.There were no difference in median OS(p=0.190),median iLPFS(p=0.334)and iRPFS(p=0.338)between the two treatment groups.In patients without EGFR-TKIs therapy(n=102),the median OS,iLPFS and iRPFS was just 19.5 months,14.8 months and 14.2 months,respectively.There were no difference in median OS(p=0.182)and median iRPFS(p=0.837)between the two treatment groups.However,the median iLPFS was significantly longer in the WBRT plus RTB group than in the WBRT alone group(16.7 vs.12.0 months,p=0.032).Conclusions:1.WBRT plus RTB significantly improved iLPFS compared with WBRT alone,especially in patients without EGFR-TKIs treatment.However,there were no significant differences in iRPFS and OS between the two groups.2.RPA class was an independent factor associated with OS and iLPFS,GPA score and EGFR-TKIs therapy were independent prognostic factors for OS,iLPFS,and iRPFS of all patients.3.NSCLC patients with BMs who have been treated with TKIs therapy may not benefit from WBRT plus RTB in terms of survival and intracranial local control.