Clinical Analysis And Gene Testing Of Lung Adenocarcinoma With Brain Metastasis

Objective: This subject mainly summarized the clinical data of patients with brain metastasis of lung adenocarcinoma for retrospective analysis.The first part of this paper retrospectively analyzed the clinical data of patients with and without brain metastasis at the first diagnosis,aiming to explore the survival situation,treatment effect and prognostic factors of patients with lung adenocarcinoma complicated with brain metastasis at different stages of time.The second part of this paper retrospectively analyzed the status quo,treatment and prognosis of EGFR/ALK/ROS1 driver gene positive,EGFR/ALK wild-type and undetected gene patients in order to explore the important role of gene testing and targeted therapy in improving the prognosis of patients with lung adenocarcinoma with brain metastasis.The last two cases were designed to explore how to achieve the best curative effect in specific clinical treatment of patients with lung adenocarcinoma with brain metastasis and the significance of molecular targeted therapy for gene detection in such patients.Methods: The first part of this study collected between January 2012 and March 2018,tianjin medical university general hospital oncology patients clinical data of 92 patients with lung adenocarcinoma,according to different time phase brain metastases,divided into the first option has a brain to turn group and the first option without brain metastases were analyzed retrospectively,in each group according to symptomatic intracranial divided into symptomatic and asymptomatic group,There are epidermal growth factor receptor(EGFR)gene mutation,anaplastic lymphoma kinase(ALK)fusion genome and no gene mutation group.Patients with the clinical characteristics and survival data including age,sex,smoking index,physical status Karnofsky score(carr's score,KPS)when the first option if there is a transfer,brain metastases from lung cancer diagnosis time,time,all the genetic testing results,with or without symptoms confirmed transfer,transfer,transfer,treatment,radiotherapy,first-line treatment effect,overall survival(OS),intracranial progression-free surial(IPFS),progression-free surial(PFS).The above data were analyzed.The quantitative indicators were described by Mean standard deviation(SD),independent sample T test was used to calculate the P value,the non-normal distribution was described byMedian Range,and the non-parametric test was used to calculate the P value.Classification indicators were described by frequency(percentage),and chi-square test or Fisher's exact test were used to compare the two groups of independent samples(if more than 20% of the cells had an expected frequency less than 5).With OS,PFS and IPFS as outcomes,patients were grouped according to whether there was brain metastasis at the first diagnosis,kaplan-meier curve was drawn,and log-rank was used to test whether the survival curve was significantly different.Cox regression was performed with OS,PFS and IPFS as the outcomes,and factors with significant single-factor results(P < 0.05)were included in the multi-factor analysis.All statistical tests were performed using a bilateral test,and a P value less than 0.05 was considered statistically significant.All data were processed using the SPSS 20.0 software package(IBM,USA).In the second part of this study,clinical data of 122 patients with lung adenocarcinoma admitted to the oncology department of tianjin medical university general hospital from August 2006 to December 2018 were collected for retrospective study.Groups were divided according to EGFR/ALK/ROS1 driver gene positive,EGFR/ALK wild type and undetected genome,and the clinical basic situation,gene testing situation,gene mutation type,first-line treatment situation,treatment and prognosis analysis of patients in each group were analyzed retrospectively.The survival indicators of each group were compared.The statistical method is the same as the first part.Results: In the first part,a total of 92 patients were enrolled,including 49 patients in the group without brain metastasis at the first diagnosis(no brain metastasis was found at the time of diagnosis of lung cancer)and 43 patients in the group with brain metastasis at the first diagnosis(brain metastasis was found at the same time after imaging objective examination at the time of diagnosis of lung cancer).The smoking index of the first brain metastasis group was significantly higher(P=0.071).According to the KPS score(Karnofsky functional status score standard),the body mass score of the group with brain metastasis at the first diagnosis was significantly worse than that of the group without brain metastasis.The right lung was the most primary tumor site in the whole group.Most of the patients with lung adenocarcinoma with brain metastasis received genetic testing,among whom 31(33.7%)had EGFR mutation.For first-line treatment,17 patients(34.7%)in the group with no brain metastasis at the first diagnosis were compared with those in the group with metastasis at the first diagnosis(5 patients,11.6%,P=0.019).First-line treatment efficacy and effective rate statistics showed that the group without brain metastasis at the first diagnosis was significantly better than the group with brain metastasis at the first diagnosis,with ORR51.0%,DCR95.9%,ORR25.6%,and DCR79.1%,respectively.Survival of patients with brain metastasis group median OS was 279 days(9.2 months),the median OS first option without brain metastasis group for 617 days(20.3 months),patients with brain metastasis group median PFS was 161 days(5.4 months),the first option without brain metastasis group median PFS was 259 days(8.6 months),OS and PFS data first option without brain metastasis group is significantly higher than the first diagnosis with brain metastasis;Survival analysis showed that the kaplan-meier curve showed that OS,IPFS and PFS in the group without brain metastasis at the first diagnosis were longer than those in the group with brain metastasis at the first diagnosis(all P <0.001).OS,PFS and IPFS Cox regression analysis: OS related factors analysis,single factor analysis showed that sex,KPS,tumor size,the best efficacy of first-line treatment,first-line treatment is involved in the operation,whether first-line treatment in radiotherapy,begin with brain metastases were has significant meaning to the OS,by multivariate analysis,the best efficacy of gender,KPS,first-line treatment,first-line treatment is involved in radiation therapy,brain metastases,etc when he first visit is still important factors related to OS;PFS related factors analysis,single factor analysis showed that the best efficacy of KPS,first-line treatment,first-line treatment is involved in the operation,begin with brain metastasis has a significant effect on PFS,by multivariate analysis,the best efficacy of first-line treatment(but not including CR vs.PD)and for the first time to see a doctor when brain metastasis is still important factors associated with PFS;Analysis of ipfs-related factors: single factor analysis showed that years of tobacco control,KPS,the best curative effect of first-line treatment,whether first-line treatment involved surgery,and brain metastasis at first diagnosis all had significant effects on IPFS;multivariate analysis showed the best curative effect of first-line treatment,and brain metastasis was still an important ipfs-related factor at the firstvisit.In the second part,a total of 122 cases of brain metastasis of lung adenocarcinoma were enrolled.(1)45 patients in the EGFR/ALK/ROS1 driver gene positive group,40 patients in the EGFR/ALK wild-type group and 37 patients in the non-gene testing group were enrolled.Age,gender and metastasis were similar in the three groups.Smoking index of the EGFR/ALK/ROS1 driver gene positive group was significantly lower than that of the EGFR/ALK wild-type group(P<0.05).KPS score(Karnofsky functional status score standard)showed no statistical difference between the three groups(P>0.05),and gene mutation was not correlated with symptoms.(2)driver gene positive subgroup analysis,EGFR/ALK/ROS1 driver gene positive group of 24 women,21 non-smokers,accounted for 46.67% of the positive driver gene group;There were 21 males and 6 non-smokers,accounting for 13.33% in the positive driver gene group.Positive EGFR/ALK/ROS1 driver gene in lung adenocarcinoma was more common in female non-smokers,while male driver gene mutation was not significantly correlated with smoking.EGFR mutation was the main gene mutation in 37 patients(82.2%).(3)in the driver gene positive group,35 patients(77.8%)were treated with targeted first-line therapy,including 18 patients with single-drug small-molecule targeted therapy.The first-line treatment in the negative gene group was mainly chemotherapy 92.5%.Among the chemotherapy regimens,59.5% were pemetrexed + platinum(cisplatin,carboplatin or nedaplatin).Thirty-seven patients with undetermined driving genome were treated with chemotherapy.(4)first-line treatment efficacy evaluation,positive driving gene group ORR 51.1%,DCR 93.3%;The ORR and DCR of the negative group were 32.5% and 87.5%,respectively.The objective remission rate of the positive group was higher than that of the negative group,and the difference was statistically significant(P<0.05).(5)prognostic indicators of the two groups: 9.3-month mPFS in the positive group and 7.7-month mPFS in the negative group,P=0.908;Driving gene positive group miPFS 10.1 months,driving gene negative group miPFS 8.2 months,P=0.730;MOS positive group was 13.3 months,and mOS negative group was 12.6 months,P=0.325.The survival benefit of the positive group was slightly higher than that of the negative group,but the difference was not statistically significant.Patients in the positivedriver gene group received first-line mPFS for 12 months in the targeted group and 8.3 months in the non-targeted group.MiPFS in the targeted group was 12 months,and miPFS in the non-targeted group was 8.3 months,P=0.042.MOS in the targeted group for 13 months,and mOS in the non-targeted group for 14.2 months,P=0.653;First-line targeted therapy for patients with positive driver genes is helpful to improve PFS and iPFS,but has no significant improvement on OS.For patients with negative driver gene,the first-line mP FS in the surgery group was 8.6 months,and the first-line mPFS in the non-surgery group was 6.5 months,P=0.034.The difference between the two groups was statistically significant.MiPFS was 8.6 months in operation group and 7.8 months in non-operation group,P=0.366.MOS in the surgery group was 14.1 months,and mOS in the non-surgery group was 12 months,P=0.479.There was no statistically significant difference between the two groups.First-line surgical treatment was helpful to improve patients' first-line PFS,but no significant improvement was found in iPFS and OS.At the time of diagnosis of brain metastasis,46 patients had symptoms of intracranial metastasis(intracranial hypertension,focal symptoms and signs,mental symptoms,meningeal irritation,epilepsy,etc.),and 21 patients received WBRT/SMART craniocerebral radiotherapy,with first-line mP FS for 9.1 months,first-line miPFS for 12 months,and mOS for 13.2 months.Twenty-five patients did not receive craniocerebral radiotherapy,with first-line mPFS of 8.2 months,first-line miP FS of 7.8 months,and mO S of 14.4 months.WBRT/SMART craniocerebral radiotherapy was used when brain metastasis was found and intracranial symptoms were present in the two groups,which could effectively improve the progression-free survival period in the skull,but did not significantly improve patients' PFS and OS.Conclusion: Part I: the higher the smoking index,the earlier the brain metastasis.Objective remission rate and disease control rate of late brain metastasis group were significantly better than early brain metastasis group.The functional status of early brain metastasis was worse than that of late brain metastasis,the number of patients receiving surgical treatment was less,and the patients' OS and PFS were shorter than that of late brain metastasis.In addition,first-line treatment effect was related to OS,and high scores of women and KPS were protective factors.Part II: the lower thesmoking index of lung adenocarcinoma brain metastasis,the higher the mutation rate of gene detection.Positive EGFR/ALK/ROS1 driver gene in lung adenocarcinoma is more common in female non-smokers,while male driver gene mutation has no significant correlation with smoking.Patients with adenocarcinoma primary to the right lung are more likely to have brain metastasis than patients with left lung.EGFR mutation was the main gene mutation of brain metastasis in lung adenocarcinoma.The first-line treatment for patients with positive driver gene was mainly targeted therapy,while the first-line treatment for patients with negative driver gene was mainly pemetrexate combined with platinum chemotherapy.The objective remission rate in the positive group was better than that in the negative group.First-line targeted therapy can improve PFS and iPFS in patients with positive driver genes.The first-line surgical treatment of patients with negative driver gene contributes to the improvement of first-line PFS in patients.The use of WBRT/SMART craniocerebral radiotherapy after symptomatic brain metastasis was associated with improved intracranial progression-free survival.Case analysis of patients with egfr-positive lung adenocarcinoma with brain metastasis: egfr-tki treatment and the comprehensive treatment based on it can benefit the patients,but drug resistance after egfr-tki treatment is inevitable,and the re-examination of pathological gene testing after drug resistance can help determine the cause of drug resistance and guide the treatment.In patients with T790 M mutation,it is relatively certain to replace third-generation TKI,but the intracranial metastasis may not develop synchronous drug resistance,so the timing of abandoning first-generation egfr-tki treatment should be cautious.The efficacy of immunotherapy in patients with EGFR mutation and NSCLC brain metastasis has yet to be determined.