Evaluation Of Efficacy And Safety Of Pemetrexed Combined With Concurrent Whole-brain Radiotherapy In The Treatment Of Lung Adenocarcinoma With Brain Metastases

Background:Lung cancer is the leading cause of death of malignant tumors,and its mortality rate is still rising year by year.The histological types of lung cancer are divided into small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC).NSCLC accounts for about 80%-85%of all cases of lung cancer,among which lung adenocarcinoma accounts for more than 50%of the total number of NSCLC,and lung adenocarcinoma is the most important pathological subtype of NSCLC.At present,the incidence rate of adenocarcinoma has increased significantly faster than that of squamous cell carcinoma.Lung adenocarcinoma has a relatively low degree of malignancy and develops slowly.However,due to the presence of micrometastases,blood channel metastasis and lymphatic metastasis have appeared even the lung lesions are small.Brain metastases are a common complication in patients with NSCLC.More than 10%of patients with NSCLC have developed brain metastases at first visit to a doctor.Patients with brain metastases have poor prognosis and poor quality of life.Patients with multiple brain metastases have a worse prognosis,with a median survival of 1-3 months without treatment.The main treatments for NSCLC with brain metastasis are surgery and whole-brain radiotherapy(WBRT).However,more than 70 percent of patients have missed the best opportunity for surgical removal by the time of diagnosis.WBRT is still the most common treatment with the advantages of wide indications,fast response and high efficiency(70-90%).The role of chemotherapy in the treatment of brain metastasis has been limited by poor efficacy and high toxicity.Most chemotherapy drugs are difficult to through the blood-brain barrier(BBB),so their efficacy on metastatic disease is highly limited.However,the BBB is disrupted when brain metastases occur.In recent years,studies have shown that pemetrexed can be detected in cerebrospinal fluid.Moreover,the combination of pemetrexed and platinum-based chemotherapy regimen obtained a good intracranial response in the treatment of NSCLC with brain metastasis.However,there are still few studies on the efficacy and side effects of pemectramine combined with concurrent WBRT in the treatment of lung adenocarcinoma with brain metastasis.Therefore,it is necesscery to further study the efficacy and safety of pemetrexed combined with WBRT in the treatment of lung adenocarcinoma with brain metastasis,it can provide more evidance for patients with brain metastasis due to lung adenocarcinoma to achieve higher survival benefits.Objective:To retrospectively study the efficacy,safety of pemetrexed combined with WBRT in the treatment of lung adenocarcinoma with brain metastasisMethods:114 patients with pathologically confirmed brain metastases due to lung adenocarcinoma in the Radiotherapy Department of Qilu Hospital of Shandong University from January 2012 to June 2019 were enrolled.According to the treatment plan,they were divided into pemetrexed+WBRT group(combined treatment group)and only WBRT group(WBRT group).The combined treatment group regimen was:Pemetrexed(500 mg/m2,d1)single drug chemotherapy combined with WBRT,at the interval of 21 days,patients received at least 6-8 cycles of chemotherapy.Radiotherapy dose is 30Gy/10-15f.Patients in the WBRT group only received WBRT,radiotherapy dose is 30Gy/10-15f.The efficacy of the combined treatment group was evaluated after every two cycles of chemotherapy,and the efficacy was determined 28 days after the completion of chemotherapy,while efficacy of the WBRT group was evaluated 2 months after the completion of radiotherapy.Results:All patients were evaluated.In the combined treatment group,there were no case of complete response(CR)and 19 cases of partial response(PR).30 cases of stable disease(SD),11 cases of progressive disease,and objective response rate(ORR)was 31.7%,and disease control rate(DCR)was 81.7%.In the WBRT group,there were 0 cases of CR,14 cases of PR,19 cases of SD and 21 cases of PD.ORR was 27.8%and DCR 63.0%.There was statistically difference between the two groups(P<0.05).The median OS of the combined treatment group and the WBRT group was 11.50 months.7.00months,respectively.There was statistically difference between the two groups(P<0.05).The main adverse efffects of the two groups were myelosuppression,gastrointestinal reactions,rash,etc.Most of adverse efffects were grade Ⅰ-Ⅱ and tolerable.The incidence of leukopenia and neutropenia in the combined treatment group was higher than that in the WBRT group,and There was statistically difference between the two groups(P<0.05).There was no statistical difference of other adverse effects between the two groups.Conclusions:The combination of pemetrexed and concurrent WBRT in the first-line treatment of patients with lung adenocarcinoma with brain metastasis has a good efficacy and safety,which is worthy of promotion.