A Study Of Treatment For Brain Metastases In Non-small Cell Lung Cancer

Part I Neurosurgery versus stereotactic radiosurgery for the treatment of non-small cell lung cancer with single brain metastasis: A systematic reviewObjectives The appropriate treatment of non-small cell lung cancer(NSCLC) with single brain metastasis(SBM) is still controversial. So we designed a systematic review to assess the efficacy of neurosurgery and stereotactic radiosurgery(SRS) for the treatment of patients with SBM from NSCLC.Methods We searched PUBMED, EMBASE, the Cochrane Library, Web of Knowledge, Current Controlled Trials, Clinical Trials and two conference websites and select NSCLC patients with only SBM who received neurosurgery or SRS. The mean median survival time(MST) was input and analyzed with SPSS18.0, and the overall survival(OS) was input and analyzed with Stata11.0.Results 18 eligible studies including 713 patients were included. The MST of the patients was 12.7 months in surgery group and 14.85 months in SRS group, respectively. The 1, 2 and 5 years OS of the patients were 59%, 33% and 19% in surgery group, and 62%, 33% and 14% in SRS group, respectively. Furthermore, in the surgery group, the 1 and 3 years OS were 68% and 15% in patients with controlled primary tumors, and 50% and 13% in the other patients with uncontrolled primary tumors, respectively. Interestingly, the 5 year OS was up to 21% in patients with controlled primary tumors.Conclusions: The MST or OS between patients treated with neurosurgery and SRS were similar. In addition, patients with resectable lung cancers and SBM may benefit from the resection of both primary lesions and metastasis.Part II Combine whole brain radiotherapy with concurrent chemotherapy for the treatment of non-small cell lung cancer with multiple brain metastases: A meta-analysis and systematic reviewObjective This meta-analysis and systematic review is aiming to evaluate the efficacy and safety of whole brain radiotherapy(WBRT) plus concurrent chemotherapy or WBRT alone for the treatment of patients with multiple brain metastases(MBM) originating from non-small cell lung cancer(NSCLC).Methods We searched PUBMED, EMBASE, Web of Science, The Cochrane Library, clinical trials and current controlled trials to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using Stata11.0 software.Results Six randomized controlled trials(RCT) involving 910 participants were included. Meta analysis showed that combination therapy was more effective at improving response rate(RR = 2.06, 95% CI [1.13, 3.77]; P = 0.019) than WBRT alone. However, combination therapy did not improve median survival time(MST)(HR = 1.09, 95%CI [0.94, 1.26]; P = 0.233) or time of neurological progression(CNS-TTP)(HR = 0.93, 95%CI [0.75, 1.16]; P = 0.543). In addition, add chemotherapy increased adverse events(Grade≥3)(RR = 2.59, 95% CI [1.88, 3.58]; P = 0.000), but did not increase the incidence of Grade 3~5 neurological or hematological toxicity(RR = 1.08, 95%CI [0.23, 5.1]; P = 0.92).Conclusion Although the combination therapy did not prolong MST or CNS-TTP, but WBRT plus chemotherapy for the treatment of NSCLC with MBM increase treatment response rates of brain metastases with limited toxicity, and further assessment is warranted.Part III The role of combine whole brain radiotherapy with target drug in non-small cell lung cancer with multiple brain metastases treatment: a systematic reviewObjective To assess the efficacy and safety of whole brain radiotherapy(WBRT) combine with targeted therapy in treatment of non-small cell lung cancer(NSCLC) with multiple brain metastases(MBM).Methods We searched PUBMED, EMBASE, The Cochrane Library, Web of knowledge, sino Med, China Academic Journal Network Publishing Database, Chinese sci-tech periodical database and Wan-fang database which studied WBRT plus target therapy versus WBRT alone for the treatment of NSCLC with brain metastases on January 4, 2014. According to Cochrane handbook for systematic reviews,two authors selected literatures, collected and extracted data independently, and data was analyzed with Rev Man5.2 software.Results Finally, 4 studies involving 332 cases were included. The results of the analysis indicated that compared with WBRT, combine with target drug showed a higher response rate(RR)(OR=2.50, 95%CI [1.21-5.16]; P=0.01), disease control rate(DCR)(OR=2.82, 95%CI [1.43-5.57]; P=0.003),intracranial disease control rate(OR=5.95, 95%CI [1.07-33.13]; P=0.04) and a longer median survival time(HR=0.67, 95%CI [0.50-0.91]; P=0.009). In safety part, add targeted therapy were frequently produce rash(OR=8.50, 95%CI [1.14-63.15]; P=0.04) and diarrhea(OR=4.51,95%CI [1.47-13.84]; P=0.008), but both of them were 1~2 grade toxicity. There were no significant difference in Hematologic toxicity(OR=0.36, 95%CI [0.02-5.88]; P=0.47), Nausea/vomiting(OR=1.15, 95%CI [0.04-30.63]; P=0.93),Fatigue(OR=0.78, 95%CI [0.29-2.09]; P=0.62) and total adverse event(OR=1.77, 95%CI [0.67-4.68]; P=0.25).Conclusion Combination therapy is superior to WBRT alone and well tolerated in the treatment of patients with multiple brain metastases from NSCLC. Duo to limitation of the included studies, more high quality randomized controlled trials is needed.