Analysis Of The Efficacy And Prognosis Of Different Treatment For Driver Gene Mutations Non-small Cell Lung Cancer With Multiple Brain Metastases

Objective: Lung cancer is the most common primary lesion of brain metastasis,especially in patients with adenocarcinoma.About 25-30% of patients with advanced non-small cell lung cancer(NSCLC)are diagnosed with brain metastases,and about 40%-50% of patients will eventually brain metastases,especially in patients with adenocarcinoma.Once with brain metastasis,the prognosis is very poor.In general,the median overall survival(mOS)is only 1-2 months.If the whole brain radiotherapy is used,the mOS of most patients can only be extended to 3-6 months.In recent years,the emergence of molecular targeted drugs such as epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)has improved the quality of life and median overall survival(mOS)in patients with NSCLC.And the toxicity adverse reaction is smaller.In many previous studies,EGFR-TKIs have shown good benefits in the treatment of primary lesions in patients with EGFR-mutant NSCLC,but the efficacy of brain metastases still needs further validation.Therefore,EGFR-TKIs alone and EGFR-TKIs combined with WBRT in the treatment of EGFR mutant NSCLC brain metastases are currently the focus of research.At the same time,for patients with advanced NSCLC brain metastases,systemic chemotherapy alone and systemic chemotherapy combined with WBRT is also widely used clinically,but it is still necessary to support the data if it can bring better benefits to patients.This study was to retrospectively analyze the optimal treatment of multiple brain metastases from EGFR mutant NSCLC,and to study the clinical application of WBRT combined with targeted drugs EGFR-TKIs and combination chemotherapy,and EGFR-TKIs alone and WBRT in patients with NSCLC brain metastases.Efficacy and toxicity.This study is aim to explore the best treatment options for patients with EGFR mutant NSCLC multiple brain metastases,to study the clinical therapeutic effects and adverse effects of WBRT combined with targeted drugs EGFRTKIs and combination chemotherapy,and EGFR-TKIs alone and WBRT in patients with NSCLC brain metastases.Methods: The clinical data of 100 patients with EGFR-mutant Lung adenocarcinoma multiple brain metastases(metastasis ≥3)admitted to our hospital were retrospectively analyzed.According to different treatment options,there were 4 groups,30 of whom were treated with EGFR-TKIs combined with WBRT(group A),30 with EGFR-TKIs monotherapy(group B),and 20 with platinum-based systemic chemotherapy combined with WBRT.(Group C),20 patients underwent WBRT alone(Group D).Targeted drugs include gefitinib,erlotinib and ectinib.The chemotherapy regimen is a platinum-based dual-drug combination chemotherapy with 21 days of 1 cycle for a total of 2-6 cycles.The dose and division method of radiotherapy:30-40Gy/10-20 f,and the amount can be increased by 10-15Gy/3-5f according to the condition.Among them,17 patients in group A received WBRT within 1 mouth from the start of targeted therapy,and 13 patients received WBRT 1 mouth after the start of targeted therapy,and targeted drugs were taken until unbearable side effects or disease progression occurred.The imaging changes of intrapulmonary tumors and intracranial metastases in each group were evaluated by enhanced CT or MRI.All patients underwent symptomatic treatment of mannitol or hormone dehydration according to the condition of intracranial hypertension during treatment.The factors that can affect the survival of EGFR mutant NSCLC brain metastasis were analyzed.The objective response rate,disease control rate,intracranial median disease progression and median survival time were compared.The evaluation of the therapeutic effect was based on the evaluation criteria of the solid tumor(Response Evaluation Criteria in Solid Tumors,RECIST version 1.1),and the adverse reactions were evaluated according to the World Health Organization(WHO)anticancer drug toxicity side reaction standard.All groups of patients were followed up by regular return visit.The efficacy of the two groups of patients was compared by X2 test,Kaplan-Meier method for survival analysis,and log-rank method was used to test the survival difference.Results: 1.100 patients can evaluate the efficacy,including complete response in 5 cases,partial response in 60 cases,stable disease in 19 cases,progressive disease in 16 cases,objective response rate(ORR)was 65%,disease control rate(disease control rate,DCR)is 84%.100 patients had a median progression free survival(mPFS)of 8 months and a mOS of 16 months.The ORR of EGFR-TKIs combined with WBRT,EGFR-TKIs monotherapy,systemic chemotherapy and WBRT was better than WBRT alone(80% vs 70% vs 60% vs 40%,P = 0.001).The ORR of group A(80%)was better than group B(70%),the difference between the two groups was statistically significant(P=0.045);the ORR of group A(80%)was better than group C(60%),the difference between the two groups was statistically significant(P=0.032);The DCR of EGFR-TKIs combined with WBRT,EGFR-TKIs monotherapy,systemic chemotherapy combined with WBRT were better than WBRT(93.3% vs90 vs 80% vs 65%,P=0.004).The DCR of Group A(93.3%)was better than group B(90%),but the difference was not statistically significant(P=0.157);The DCR of group A(93.3%)was better than group C(80%),but the difference between the two groups was not statistically significant(P=0.074).2.Intracranial mPFS of EGFR-TKIs in combination with WBRT,EGFR-TKIs monotherapy,systemic chemotherapy and WBRT was superior to WBRT alone(13 months vs 11.5 months vs 7.5 months vs 2.5 months,P= 0.002).In group A,intracranial mPFS(13 months)was better than group B(11.5 months),the difference was statistically significant(P=0.018);The intracranial mPFS of group A(13 months)was better than group C(7.5 months),the difference between the two groups was statistically significant(P=0.009).3.The mOS of EGFR-TKIs combined with WBRT,EGFR-TKIs monotherapy,systemic chemotherapy and WBRT was better than WBRT alone(24 months vs22.5 months vs17.5 months vs 5.5 months,P=0.000).The mOS of group A(24 months)was better than group B(22.5 months),but the difference was not statistically significant(P=0.054);the mOS of group A(24 months)was better than group C(17.5 months),the difference between the two groups was statistically significant(P = 0.001).4.Subgroup analysis of patients with EGFR-TKIs plus WBRT,17 patients received WBRT(early radiotherapy group)within 2 weeks from the start of targeted therapy,and 13 patients received WBRT(late radiotherapy group)2 weeks after the start of targeted therapy.The ORR of the two groups were 82.3% and 76.9%,respectively,but the difference was not statistically significant(P=0.090).The DCR of the two groups was 94.1% and 92.3%,respectively,but the difference was not statistically significant(P=0.198);The intracranial mPFS of the two groups were 14.5 months and 11.5 months,respectively,and the difference was statistically significant(P=0.044).The mOS of the two groups were 25.5 months and 22.5 months,respectively,and the difference was statistically significant(P= 0.024).5.KPS score(P = 0.000),different treatment options(P = 0.000)can affect the survival of NSCLC.There was no significant difference in gender,age distribution,smoking history,presence or absence of central nervous system symptoms,EGFR mutation type,and metastatic lesion location(P>0.05).6.All subjects did not develop intolerable toxic side effects during the treatment.The most common adverse reaction in EGFR-TKIs combined with WBRT was acne-like rash,which was significantly higher than systemic chemotherapy combined with WBRT,and the difference was statistically significant(P=0.006).The most common adverse reactions in Systemic chemotherapy combined with WBRT were myelosuppression and gastrointestinal reactions,and the incidence was significantly higher than that of EGFRTKIs plus WBRT,and the difference was statistically significant(P=0.003).Conclusion:1.Different treatment have significant effects on short-term efficacy and long-term survival in patients with EGFR-mutant Lung adenocarcinoma multiple brain metastases.The short-term efficacy and long-term survival of patients treated with EGFR-TKIs combined with WBRT were superior to those of systemic chemotherapy combined with WBRT,and the incidence of adverse reactions was low,tolerance was acceptable,and safety was high.2.On the basis of EGFR-TKIs,combined WBRT can improve the objective response rate and intracranial median disease-free survival,but there is no significant difference in the overall survival of the two group.3.When EGFR-TKIs combined with WBRT,there is no significant difference in the objective response rate and disease control rate between early radiotherapy and late radiotherapy,but early radiotherapy can improve the intracranial median disease-free progression and median overall survival in patients with EGFR-mutant Lung adenocarcinoma multiple brain metastases.4.KPS scores and different treatment regimens have important effects on the prognosis of patients with EGFR-mutant Lung adenocarcinoma multiple brain metastases.Patients with KPS≥70,EGFR-TKIs combined with WBRT have a better prognosis.