Clinical Study On The Treatment Modes,Prognosis And Side Effects Of Radiotherapy For Brain Metastasis From Lung Cancer

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The investigation of the current situation of local treatment mode of brain metastasis from lung cancer and the establishment of prognostic evaluation modelObjective:To evaluate the current situation of local treatment of brain metastasis of lung cancer,to analyze the insufficients of diagnosis and treatment currently,and to establish a new prognostic model.Methods:A retrospective analyze was used to collect the clinical data of 313 patients with brain metastasis of lung cancer who were admitted to the Radiotherapy Department of the Second Affiliated Hospital of Soochow University from January 2014 to December 2018 were recorded in the retrospective study.The local treatments of patients suffering the brain metastasis were analyzed and compared among different years and counts of brain metastasis,separately.The survival curves were estimated by the Kaplan-Meier method and compared using the two-sided log-rank test.Multivariate Cox regression was used to assess the correlations between clinical factors and prognosis.Finally the new prognostic model was established and the effectiveness was evaluated.Results:(1)From 2014 to 2018,56%to 100%lung cancer patients with brain metastasis in our radiotherapy department were treated with local brain radiotherapy including the whole brain radiotherapy(WBRT),WBRT combined with local radiotherapy and local radiotherapy.The proportion of patients who chose these treatments showed a downward trend,especially in WBRT combined with local radiotherapy.However,the proportion of patients who chose molecular targeted therapy showed an upward trend during this period.(2)From 2014 to 2018,significant difference(P=0.007)was observed when comparing the treatment modes among patients with different numbers of intracranial metastasis of lung cancer.More than half(51.2%)of the patients which had more than 3 intracranial metastases received WBRT.About 1/3(34.9%)of patients which had less than 3 intracranial metastases received WBRT and about 1/3(31.8%)received both WBRT combined with local radiotherapy.(3)From 2014 to 2018,over 60%patients with less than or equal to 3 brain metastases chose brain radiotherapy,among which the proportion of patients who chose WBRT was about 40%,showing a slight downward trend;the proportion of patients who chose WBRT combined with local radiotherapy decreased,while the proportion of patients with local radiotherapy was the lowest but showed an upward trend.In addition,the proportion of patients who chose molecular targeted therapy and other treatment methods was basically stable.(4)From 2014 to 2018,the proportion of the patients with more than 3 brain metastases undergoing local brain radiotherapy fluctuated from 50%to 100%,showing a general downward trend,and the proportion of patients who chose WBRT was about 50%,showing a slight downward trend;The proportion of patients who chose WBRT combined with local radiotherapy showed a significant downward trend;The proportion of patients who chose local radiotherapy was less than 5%,which was the lowest in the five years.In addition,the proportion of patients who chose molecular targeted therapy was on the rise.(5)Univariate analysis showed that gender(P=0.039),age(P=0.002),pathological type(P=0.005),KPS(P<0.001),the time of brain metastasis(P=0.004),brain radiotherapy(P=0.007)and molecular targeted therapy benefit(P<0.001)were related to the prognosis of patients with brain metastasis of lung cancer.(6)The multivariate Cox regression analysis demonstrated that KPS,molecular targeted therapy,the time of brain metastasis and brain radiotherapy were independent prognostic factors for brain metastasis of lung cancer(all P<0.05).(7)A new prognostic model of lung cancer patients with brain metastasis was established by KPS,molecular targeted therapy,the time of brain metastasis and brain radiotherapy.The area under the ROC curve assessed at 3,6 and 12 months was larger than RPA,GPA and Lung-molGPA,suggesting the sensitivity and specificity of the novel model were much better than the traditional models.The yoden index showed the highest calculated by the new model among these models.Conclusion:(1)From 2014 to 2018,the local treatment modes for lung cancer patients with brain metastasis in the Department of Radiotherapy of our hospital basically met the requirements of various specifications and guidelines.(2)From 2014 to 2018,the proportion of lung cancer patients with brain metastasis in our radiotherapy department who chose brain radiotherapy gradually decreased,while the proportion of patients who chose molecular targeted therapy was on the rise.(3)From 2014 to 2018,radiotherapy including WBRT remains to be the most important local treatment method for lung cancer patients with brain metastasis in Department of Radiotherapy of our hospital.(4)KPS,the time of brain metastasis,the status of brain radiotherapy and the benefit of molecular targeted therapy are the independent prognostic factors of lung cancer patients with brain metastasis.(4)The new model is suitable for the prognosis evaluation of lung cancer patients with brain metastasis,because of its sensitivity,specificity and the potent of higher efficacy comprared to RPA,GPA and Lung-molGPA.Part ? Analysis of prognostic risk factors in brain metastasis of lung adenocarcinomaObjective:To analyze the risk factors related to prognosis of brain metastasis of lung adenocarcinoma.Methods:A retrospective study was conducted in 231 patients with brain metastasis of lung adenocarcinoma admitted to the Radiotherapy Department of the Second Affiliated Hospital of Soochow University from January 2014 to December 2018.The clinical data of the patients were collected and the survival time was followed up.According to the time interval between the diagnosis of lung adenocarcinoma and the detection of brain metastasis,the patients were divided into two groups:simultaneous brain metastasis group(brain metastasis was found at the same time of the diagnosis of lung adenocarcinoma)and heterochronous brain metastasis group(brain metastasis was found later than the diagnosis of lung adenocarcinoma).Kaplan-Meier method was used to calculate the survival rate of patients and Log-rank method was used to perform statistical test.The multivariate Cox regression was used to analyze the correlations between patients' survival and the multiple factors.Result:(1)Among 231 patients with brain metastasis of lung adenocarcinoma,106(45.9%)had simultaneous brain metastasis and 125(54.1%)had heterochronous brain metastasis.(2)The median survival time of the patients with brain metastasis of lung adenocarcinoma was 10.0 months.The survival rates of 6,12 and 24 months after the diagnosis of brain metastasis were 62.7%,40.7%and 14.0%,respectively.The median survival time of patients with simultaneous brain metastasis was 13.0 months,and the survival rates of 6,12 and 24 months after the diagnosis of brain metastasis were 75.0%,50.0%and 22.1%,respectively.The median survival time of patients with isochronous brain metastasis was 7.5 months,and the survival rates of 6,12 and 24 months after the diagnosis of brain metastasis were 52.4%,32.9%and 8.5%.(3)The univariate analysis showed that age<70 years old(P=0.012),KPS? 70(P=0.001),the time of brain metastasis(P=0.009),RPA(P<0.001),GPA(P=0.014)and treatment modes(P<0.001)were related to the prognosis of patients with brain metastasis of lung adenocarcinoma.The multivariate Cox regression analysis showed that KPS,the time of brain metastasis,brain radiotherapy and the treatment modes were the independent prognostic factors(all P<0.05).(4)In patients with simultaneous brain metastasis,both univariate analysis and multivariate Cox regression analysis showed that clinical symptoms of nervous system,RPA and treatment modes were independent prognostic factors(all P<0.05).(5)The univariate analysis showed that KPS(P<0.001),EGFR sensitive mutation status(P=0.039),number of brain metastases(P=0.029),clinical symptoms of nervous system(P=0.017),RPA(P<0.001),GPA(P=0.009)and treatment modes(P<0.001)were related to the prognosis of patients with heterochronous brain metastasis.The multivariate Cox regression analysis showed that the treatment modes,KPS and the number of brain metastases were independent prognostic factors for patients' survival(all P<0.05).Conclusion:(1)KPS,brain radiotherapy,the time of brain metastasis,and the treatment modes are independent prognostic factors.The patients with simultaneous brain metastasis,KPS?70,molecular targeted therapy combined with craniocerebral radiotherapy and WBRT combined with local craniocerebral radiotherapy demonstrated a better long-term survival.(2)RPA,neurological symptoms and treatment modes are independent prognostic factors in the lung adenocarcinoma patients with simultaneous brain metastasis.The prognosis of patients with low RPA grade and neurological symptoms as well as molecular targeted therapy combined with craniocerebral radiotherapy is better.(3)The treatment modes,KPS and the number of brain metastases are independent prognostic factors in the lung adenocarcinoma patients with heterochronous brain metastasis.The patients with the molecular targeted therapy combined with craniocerebral radiotherapy,KPS?70,and less than 3 intracranial metastases show a better prognosis.Part ? The clinical study of the effect of WBRT on cognitive function of patients with brain metastasis of lung cancerObjective:To explore the influence of WBRT on cognitive function and activities of daily life of patients with brain metastasis of lung cancer.Methods:102 lung cancer patients with brain metastases(BM)group and 41 lung cancer patients with non-brain metastases(NBM)group who were admitted to the Radiotherapy Department of the Second Affiliated Hospital of Soochow University from January 2014 to December 2016 were selected as the objects.Montreal cognitive assessment scale(MoCA)and mini mental state scale(MMSE)were used to assess the cognitive function of the patients;alzheimer's disease cooperative study-acitvites of daily living inventory(ADCS-ADL)was used to assess the activities of daily living of the patients;CT and/or MRI were used to determine the characteristics of the patients with intracranial tumors.SPSS 25.0 was used to analyze the correlation between the characteristics of intracranial lesions and the level of cognitive function in patients with brain metastasis of lung cancer.Result:(1)According to MoCA assessment,in BM group,there were 93 patients(91.2%)with cognitive impairment,70 patients(68.6%)with mild cognitive impairment(MCI),23 patients(22.6%)with dementia,and 31 patients(75.6%)with cognitive impairment in NBM group.According to MMSE assessment,in BM group,48 patients(47.1%)had cognitive impairment,21 patients(20.6%)had MCI,27 patients(26.5%)had dementia,and 11 patients(26.8%)with cognitive impairment in NBM group.The proportion of patients with cognitive impairment in BM group was higher than that in NBM group,and the difference was statistically significant(P<0.05);the MoCA scores and MMSE scores in BM group were lower than that in NMB group and the difference was statistically significant(all P<0.05).(2)The gender could influence the cognitive function of patients with brain metastasis before WBRT(P=0.005),while age,the number of chemotherapy before diagnosis of brain metastasis,the time from the diagnosis of primary tumor to the occurrence of brain metastasis couldn't influence the cognitive function of patients with brain metastasis before WBRT(normal,MCI,dementia)(all P>0.05).The pathological classification of lung cancer could affect the cognitive function of patients assessed by MoCA(P>0.010)but not by MMSE(P=0.123).(3)There was no significant correlation between the volume of brain metastases,the volume of total edema zone,the number of involved lobes and the level of cognitive function in patients with brain metastases from lung cancer before WBRT(P>0.05),but there was a positive correlation between the number of brain metastases and the level of cognitive function in patients with brain metastases from lung cancer before WBRT(normal cognitive function was grade 1,MCI was grade 2,dementia was grade 3)(all P<0.05),negatively correlated with MoCA and MMSE scores(all P<0.05)(4)There were significant differences in cognitive function(MoCA socres and MMSE scores)among the groups with brain metastasis involving different hemispheres(all P<0.05).The proportion of dementia in the patients with brain metastasis involving bilateral hemispheres was significantly increased.(5)There were significant differences in cognitive function(MoCA scores and MMSE scores)among the groups with brain metastasis involving different number of lobes(all P<0.05).(6)The cognitive function level(MoCA scores and MMSE scores)of patients with more than 3 brain metastases was significantly lower than that of patients with less than 3 brain metastases(both P<0.05).(7)After WBRT,the cognitive function of patients with brain metastases from lung cancer was improved by MoCA(P=0.003)but not by MMSE(P=0.370).The cognitive function of patients with brain metastases from lung cancer at 3 months,6 months and above after WBRT was improved by MOCA(all P<0.05),but not by MMSE(all P>0.05).(8)There was significant difference in the total scores of MOCA and MMSE between the pre WBRT group and the post WBRT group(MoCA:18.9±5.8 points vs.21.4±7.8 points,P=0.028;MMSE:23.7±5.2 points vs.25.9±8.1 points,P=0.040),but there was no significant difference in the cognitive function scores of the patients assessed three months after radiotherapy compared with that before radiotherapy(MoCA:18.9±5.8 points vs.20.2±5.6 points,P=0.263;MMSE:23.7±5.2 points vs.23.8±5.2 points,P=0.938).The scores of 6 months after radiotherapy were significantly improved(MoCA:18.9±5.8 points vs.22.3±9.3 points,P=0.010;MMSE:23.7±5.2 points vs.27.6±9.7 points,P=0.003).(9)The ADCS-ADL scores of the two groups before and after WBRT were 55.4±17.4 points vs.60.8±14.2 points respectively.The difference was statistically significant(P=0.028).Conclusion:(1)Before WBRT,most of the patients with brain metastasis of lung cancer have different degrees of cognitive impairment,among which MCI was the main one.(2)The cognitive dysfunction of patients with brain metastasis of lung cancer is related to gender,pathological classification of lung cancer,the involvement of intracranial lesions in the cerebral hemisphere and the number.(3)The overall cognitive function and activities of daily living of patients with brain metastasis from lung cancer can be improved after 6 months of WBRT.(4)MoCA is more sensitive than MMSE in the screening of cognitive impairment in patients with brain metastasis of lung cancer.