Assessment Of Local Failure And Survival Analysis After Intracranial Radiotherapy Of Brain Metastases

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Survival analysis of Brain Metastases from Breast CancerBackground and purposeThe prognosis of solid tumor brain metastases(BM)is significantly different from primary tumors.This study aims to explore the rational optimization of comprehensive treatment strategies for patients with breast cancer brain metastases(BCBM)based on the individualized systemic treatment guided by molecular subtype.MethodRetrospectively collected clinical pathological data of 111 patients diagnosed of BCBM and receiving intracranial radiotherapy from Aug 2009 to Nov 2017 in our hospital.All patients were diagnosed with BM with brain MRI.Among them,1 patient was male and 110 were female.The median age at the diagnosis of BM was 54 years.The molecular subtype was as follows:Luminal A in 16 cases,Luminal B in 47 cases,triple negative breast cancer(TNBC)in 27 cases,HER2 overexpression in 19 cases,and the other 2 cases were unknown.Eighty-three patients received initial whole brain radiotherapy(WBRT)after breast cancer(BC),and 28 patients received stereotactic radiosurgery(SRS).The differences in biological characteristics of patients with different molecular subtype and related prognostic factors after BM were analyzed.ResultThe median time from initial diagnosis to brain metastases(TTBM)in patients with Luminal A,Luminal B,TNBC,and HER2 overexpression were:56.2 months,42.7 months,21.1 months,and 14.1 months.The median overall survival(OS)after BM was 12.8±1.5 months.The median OS for Breast cancer-Graded Prognostic Assessment(Breast-GPA)scores 0-1.0,1.5-2.0,2.5-3.0,and 3.5-4.0 were 6.5 months,9.9 months,14.4 months,and 24.5 months,respectively(P=0.007).Univariate and multivariate analysis showed that KPS score?70,infra-tentorial involvement,extracranial metastases(ECM),and without contining systemic therapy were independent risk factors(P=0.004,P=0.006,P=0.003,and P<0.001).In hormone receptor-positive patients,the median OS for patients receiving continuing endocrine therapy after BM was significantly longer than those who did not receive endocrine therapy(20.9 months and 10.8 months,P=0.001).In HER2-positive patients,median OS after BM was increased from 5.6 months to 24.5 months with anti-HER2 therapy,P=0.001.In the group with Breast-GPA 0-2.0,upfront intracranial radiotherapy could increase the median OS from 3.3 months to 9.8 months,P=0.04.ConclusionThe median TTBM in HER2 overexpressing and TNBC patients was significantly shorter than that of Luminal-like BC.Breast-GPA score divided patients into four groups with significantly different survival.For BCBM patients with better physical performance,continuing systemic therapy after WBRT without infra-tentorial involvement and extracranial metastasis were associated with better OS.Defferal radiotherapy may be not suitable for unfavorable prognostic patients,such as Breast-GPA subgroup 0-2.0.Part ? Survival analysis of brain metastases from non-small cell lung cancerBackground and purposeLung cancer is the first primary tumor of brain metastases(BM).The advancement of targeted therapy driven by gene-driven genes has changed the natural course of lung cancer BM,especially for non-small cell lung cancer(NSCLC)BM.In this study,we retrospectively analyzed NSCLC patients with BM in order to find the prognostic factors,and further explore the guiding value of Lung cancer-Graded Prognostic Assessment(Lung-GPA)in comprehensive treatment of BM in patients with lung cancer.MethodThe clinical data of NSCLC patients diagnosed with BM and treated in our hospital from Jan 2008 to Oct 2017 were retrospectively collected.All the 218 patients with primary or metastatic lesions were confirmed of NSCLC,and were diagnosed of BM by enhanced MRI.Among them,167(76.6%)patients were adenocarcinomas and 22(10.1%)squamous cell carcinomas.A total of 63 patients underwent EGFR gene detection,of them 42 were EGFR-mutant and 21 were wild type.One hundred and fifty-seven patients received initial whole brain radiotherapy(WBRT)after BM,and 61 patients received stereotactic radiosurgery(SRS).ResultThe median follow-up of the surviving patients was 38.5 months,and the median overall survival(OS)after BM was 18.1 ±1.7 months.The median OS of Lung-GPA scores 0-1.0,1.5-2.0,2.5-4.0 was 13.4 months,20.3 months,and 33.6 months,respectively(P<0.001).Univariate and multivariate analysis showed that receiving lung surgical treatment,KPS>70,without infra-tentorial involvement,and continuous systemic therapy were independent prognostic factors for improved OS after BM(P=0.024,P=0.001,P=0.013 and P<0.001).The use of EGFR-TKIs after BM increased the median survival time of EGFR-mutant patients from 9.3 months to 22.4 months(P<0.001)for 42 EGFR-mutantion patients.The survival benefit of EGFR-TKIs na?ve patients was better than those who had previously received EGFR-TKIs(8.9 months and 30.8 months,P<0.001).In the Lung-GPA 0-1.5 group,continuous systemic therapy after intracranial radiotherapy improved survival(9.2 months and 13.0 months,P=0.035).In the entire group,148 patients died during follow-up,of whom 64 died of intracranial progression and 84 died of extracranial progression.The proportion of patients who died of extracranial progression for patents with or without EGFR-TKIs after BM was 28.6%and 75.0%,respectively,P=0.047.ConclusionIn addition to traditional prognostic factors such as control of the primary tumor and KPS scores,without infra-tentorial involvement and continuous systemic therapy patients were associated with better OS.Besides,for the subgroup of Breast-GPA score 0-1.5,The benefit of continuous systemic therapy after intracranial radiotherapy is even more significant;the use of EGFR-TKIs prolonged survival after BM,and this benefit is more pronounced in EGFR-TKIs naive patients.Part ? Analysis of intracranial failure after radiotherapy for brain metastasesBackground and purposeSolid tumor brain metastases(BM)refer to the primary extracranial malignant tumors thansfer to the brain.Due to the presence of mass effects and the emergence of corresponding physical signs,the prognosis of BM patients is poor.Whole brain radiotherapy(WBRT)plays an important role in the local treatment of BM.In recent years,with the development of stereotactic radiotherapy(SRS)and the continuous progress of systemic therapy,the comprehensive treatment model of BM has undergone a tremendous evolution.The use of initial SRS for BM was reported an increased risk of subsequent intracranial faliure compared with WBRT.This study was designed to compare the intracranial failure patterns between initial WBRT and initial SRS patients and explore the value of initial intracranial local treatment in BM patients.MethodsThe clinical pathological data of 178 BM patients from Jan 2008 to Nov 2017 who received intracranial radiotherapy in our hospital were retrospectively reviewed.The primary tumor was lung cancer in 120 patients and breast cancer in 58 patients.After BM,there were 60 patients receiving SRS,and WBRT for 118 patients.Intracranial progression free survival(PFS)was estimated using the Kaplan-Meier product limit method.The univariate analysis was used by the mean of the Log rank method,and a multivariate analysis was performed by Cox regression model.P<0.05 was considered significantly.ResultThe median follow-up was 15.4 months(1.43-84.7 months)and 29.4 months for surviving patients.The median age at the diagnosis of BM was 59 years(22-81 years).The median intracranial PFS for the entire group was 12.2±1.1 months.The median intracranial PFS of the initial SRS and the initial WBRT group was 7.9 months and 13.4 months,respectively(P<0.001).Univariate and multivariate analysis showed that the number of intracranial lesions>3 and the initial SRS after BM were independent risk factors for shorter intracranial PFS.The intracranial distant failure rate in the initial SRS group and the initial WBRT group was 46.7%(28 cases)and 21.2%(25 cases),respectively(P<0.001).The median overall survival after intracranial radiotherapy in the initial SRS and WBRT groups was 19.3 months and 16.1 months,respectively(P=0.37).In 28 patients with 1-3 brain metastatic lesions and no extracranial metastases(ECM),the median intracranial PFS after initial SRS and initial WBRT was 14.6 months and 12.2 months(P=0.095),and the median overall survival was 30.2 months and 41.5 months,respectively(P=0.95).ConclusionOur study further confirmed that patients with more than 3 brain metastatic lesions have a higher risk of intracranial progression after receiving SRS.For this group of patients,the clinical application of initial SRS should be cautious.SRS without WBRT could be used as the initial intracranial radiotherapy option for patients with 1-3 intracranial metastases and no ECM.