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Meta-analysis of efficiency and safety of WBRT±temozolomide in treatment of brain metastases from NSCLC
Luo Qing1, Chen Fang1, Chen Xumei1, Leng Yuanxiu1, Li Ning2, Zou Yan2, Hu Wei2, Pan Yana3
1. Oncology Laboratory,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,China;2. Tumor Hospital of Affiliated Hospital of Zunyi Medical University,Zunyi 563000,China;3. Hematology and Oncology Department,Fifth Affiliated Hospital of Zunyi Medical University,Zhuhai 519000,China
AbstractObjective To compare the efficacy and safety between whole brain radiotherapy (WBRT) and WBRT combined with temozolomide (TMZ) in the treatment of non-small cell lung cancer with brain metastases. Methods According to the retrieval strategy,the Chinese and English literatures before February 2018 were retrieved from EMbase,Cochrane,PubMed,Wanfang database,Chongqing VIP and CNKI,The target literatures were selected according to the inclusion and exclusion criteria,The quality of the included studies and extracted data was independently assessed by 3 researchers,The RevMan 5,3 and STATA 12,0 software was used for statistical analysis,The Objective remission rate (ORR),the total survival period (OS),the progression-free survival (PFS),and the side effects of chemotherapy were evaluated. Results In total,17 trials consisting of 1128 patients were included,The Results of Meta-analysis demonstrated that compared with the WBRT group,the ORR was significantly higher (OR=2.54;95%CI:1.93-3.36;P<0.001),the PFS was significantly longer (MSR=1.329;95%CI:1.143-1.545;P<0,001),and the incidence of hematological toxicity (OR=3.44;95%CI:1.63-7.26;P<0.05) and the gastric intestinal reaction (OR=1.69;95%CI:1.24-2.31;P<0.05) was significantly higher in the WBRT+TMZ group,The heterogeneities were within the acceptable range with statistical significance,The Results of OS were invalid due to relatively large heterogeneity,The incidence of headache did not significantly differ between two groups (OR=1.05;95%CI:0.72-1.55;P=0,79). Conclusions Compared with WBRT alone,WBRT combined with TMZ is beneficial to improve the short-term efficacy,whereas the incidence of hematological toxicity and gastrointestinal reaction is higher,The occurrence of headache does not significantly differ between two groups,The benefit of long-term survival remains uncertain.
Fund:National Natural Science Foundation of China (81260397);Science and Technology Fund of Department of Science and Technology of Guizhou Province (Q-J[2013]2331);Provincial-Municipal Joint Project of Zunyi Municipal Science and Technology Bureau[Z (2014) 9];Fund for Outstanding Scientific and Technological Innovation Talents in Universities of Department of Education of Guizhou Province (Q-KY[2015] 495)
Corresponding Authors:
Pan Yana,Email:137170573@qq.com.
Cite this article:
Luo Qing,Chen Fang,Chen Xumei et al. Meta-analysis of efficiency and safety of WBRT±temozolomide in treatment of brain metastases from NSCLC[J]. Chinese Journal of Radiation Oncology, 2019, 28(5): 326-333.
Luo Qing,Chen Fang,Chen Xumei et al. Meta-analysis of efficiency and safety of WBRT±temozolomide in treatment of brain metastases from NSCLC[J]. Chinese Journal of Radiation Oncology, 2019, 28(5): 326-333.
[1] Barnholtz-Sloan JS,Sloan AE,Davis FG,et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the metropolitan detroit cancer surveillance System[J].J Clin Onsol,2004,22(14):2865-2872.DOI:10.1200/JCO.2004.12.149. [2] Patel M,McCully C,Godwin K,et al. Plasma and cerebrospinal fluid pharmacokinetics of intravenous temozolomide in non-human primates[J].J Neurooncol,2003,61(3):203-207.DOI:10.1023/A:1022592913323. [3] Wilhelm I,Molnár J,Fazakas C,et al. Role of the blood-brain barrier in the formation of brain metastases[J].Int J Mol Sci,2013,14(1):1383-1411.DOI:10.3390/ijms14011383. [4] Rudat V,El-Sweilmeen H,Brune-Erber I,et al. Identification of breast cancer patients with a high risk of developing brain metastases:a single-institutional retrospective analysis[J].BMC Cancer,2014,14:289.DOI:10.1186/1471-240 7-14-289 [5] Costa DB,Kobayashi S,Pandya SS,et al. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib[J].J Clin Oncol,2011,29(15):e443-445.DOI:10.1200/JCO.2010.34.1313. [6] Barazzuol L,Jena R,Burnet NG,et al. Evaluation of poly (ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma[J].Radiat Oncol,2013,8(1):1-11.DOI:10.1186/1748-717X-8-65. [7] Stupp R,Gander M,Leyvraz S,et al. Current and future developments in the use of temozolomide for the treatment of brain tumours[J].Lancet Oncol,2001,2(9):552-560.DOI:10.1016/S1470-2045(01)00489-2. [8] 蒲廷,靳雨,李光明,等,全脑放疗联合替莫唑胺治疗非小细胞肺癌脑转移的Meta分析[J].西部医学,2017,29(1):70-77.DOI:10.3969/j.issn.1672-3511.2017.01.015. Pu T,Jin Y,Li GM,et al. Meta-analysis of whole brain radiotherapy combined with temozolomide in the treatment of brain metastsis[J].Med J West Chin,2017,29(1):70-77.DOI:10.3969/j.issn.1672-3511.2017.01.015. [9] 廖恺,毕卓菲,何艳,等.全脑放疗联合替莫唑胺治疗非小细胞肺癌脑转移的荟萃分析[J].中华医学杂志,2012,92(45):3199-3203.DOI:10.3760/cma.j.issn.0376-2491.2012.45.011. Liao K,Bi ZF,He Y,et al. A meta-analysis of whole brain radiotherapy combined with temozolomide in the treatment of brain metastsis[J].Chin Med J,2012,92(45):3199-3203.DOI:10.3760/cma.j.issn.0376-2491.2012.45.011. [10] Tian J,Luo Y,Xiang J,et al. Combined treatment for non-small cell lung cancer and breast cancer patients with brain metastases with whole brain radiotherapy and temozolomide:a systematic review and meta-analysis[J].J Neurooncol,2017,135(2):217-227.DOI:10.1007/s11060-017-2572-z. [11] D. Antonadou,N.Coliarakis. A,et al.multi-institutional trial comparing survival of patients with brain metastases from lung cancer treated with temozolomide plus radiotherapy versus to radiotherapy alone[J].Lung Cancer,2003.41(5):S22-S23.DOI:10.1016/S1359-6349(03)90802-0. [12] Chua D,Krzakowski M,Chouaid C,et al. Whole-brain radiation therapy plus concomitant temozolomide for the treatment of brain metastases from non-small-cell lung cancer:a randomized,open-label phase Ⅱ study[J].Clin Lung Cancer,2010,11(3):176-181.DOI:10.3816/CLC.2010.n.022. [13] Hassler MR,Pfeifer W,Knocke-Abulesz TH,et al. Temozolomide added to whole brain radiotherapy in patients with multiple brain metastases of non-small-cell lung cancer:a multicentric Austrian phase Ⅱ study[J].Wien Klin Wochenschr,2013,125(15-16):481-48.DOI:10.1007/s00508-013-0402-7. [14] 谢家印,向德兵,王阁,等.替莫唑胺联合全脑放疗治疗非小细胞肺癌脑转移临床研究[J].重庆医学,2007,(19):1941-1942.DOI:10.3969/j.issn.1671-8348.2007.19.012 Xie JY,Xiang DB,Wang G,et al. Clinical study of Temozolomide Combined with whole brain radiotherapy for brain metastasis of non-small cell lung cancer[J].Chongqing Med,2007,(19):1941-1942.DOI:10.3969/j.issn.1671-8348.2007.19.012. [15] 曾毅,罗林,袁红平,等.替莫唑胺同步放疗治疗非小细胞肺癌脑转移 32例观察[J].云南医药,2009(3):374-375. Zeng Y,Luo P,Yuan HP,et al. Observation of 32 cases of brain metastasis from non-small cell lung cancer treated with temozolom[J].Yunnan Med Pharm,2009(3):374-375. [16] 周蕾,安广宇,岳振东,等.替莫唑胺联合放疗在非小细胞肺癌脑转移中的临床研究[J].中国药房,2011(22):2072-2074. Zhou L,An GY,Yue ZD,Chen L,Song YG,Jiang N.Clinical study of Temozolomide Combined with radiotherapy in non-small cell lung cancer with brain metastases[J].Chin Pharmacy,2011(22):2072-2074. [17] 石磊,习隽丽,曾伟.替莫唑胺联合放疗非小细胞肺癌脑转移瘤疗效观察[J].现代中西医结合杂志,2014(27):3002-3004.DOI:10.3969/j.issn.1008-8849.2014.27.015. Shi L,Xi JL,Zeng W.Clinical observation of Temozolomide Combined with radiotherapy for non-small cell lung cancer with brain metastases[J].Mod J Integrat Tadit Chin West Med,2014(27):3002-3004.DOI:10.3969/j.issn.1008-8849.2014.27.015. [18] 杨海林.非小细胞肺癌脑转移放疗联合替莫唑胺的疗效评价[J].中国现代药物应用,2015(17):132-133.DOI:10.14164/j.cnki.cn11-5581/r.2015.17.098. Yang HL.Clinical evaluation of radiotherapy combined with temozolomide for non-small cell lung cancer with brain metastases[J].Chinese Journal of Modern Drug Application.2015(17):132-133DOI:10.14164/j.cnki.cn11-5581/r2015.17.098. [19] 谷田露.非小细胞肺癌脑转移者应用替莫唑胺联合全脑放疗的随机对照研究[J].现代仪器与医疗,2015(1):36-38.DOI:10.11876/mimt201501012. Gu TL.Randomized controlled study of Temozolomide Combined with whole brain radiotherapy in patients with non-small cell lung cancer with brain metastases[J].Mod Instr Med Treat,2015(1):36-38.DOI:10.11876/mimt201501012. [20] 孙宗文,张妍.颅脑放疗联合替莫唑胺治疗非小细胞肺癌脑转移 30例[J].肿瘤学杂志,2016,22(1):53-56.DOI:10.11735/j.issn.1671-170X.2016.01.B011. Sun ZW,Zhang Y.Craniocerebral radiotherapy combined with temozolomide in the treatment of 30 cases of non-small cell lung cancer with brain metastases[J].J Oncol,2016,22(1):53-56.DOI:10.11735/j.issn.1671-170X.2016.01.B011. [21] 支卫国.替莫唑胺辅助全脑放疗非小细胞肺癌脑转移瘤的临床效果[J].中国实用神经疾病杂志,2016,19(23):91-92.DOI:10.3969/j.issn.1673-5110.2016.23.053. Zhi WG.Clinical effect of temozolomide assisted whole brain radiotherapy for non-small cell lung cancer with brain metastases[J].Chin J Pract Nerv Dis,2016,19(23):91-92.DOI:10.3969/j.issn.1673-5110.2016.23.053. [22] 刘哲,替莫唑胺联合放疗治疗非小细胞肺癌脑转移瘤的临床研究[J].中国现代药物应用,2016,10(2):114-115.DOI:10.11735/j.issn.1671-170X.2016.01.B011. Liu Z.Clinical study of Temozolomide combined with radiotherapy in the treatment of non-small cell lung cancer with brain metastases[J].Chin J Mod Drug Appl,2016,10(2):114-115.DOI:10.11735/j.issn1671-170X.2016.01.B011. [23] 穆昱.替莫唑胺联合放化疗非小细胞肺癌脑转移的临床效果分析[J].中国继续医学教育,2016,8(12):139-140.DOI:10.3969/j.issn.1674-9308.2016.12.100. Mu Y.Clinical analysis of Temozolomide combined with radiotherapy and chemotherapy in non-small cell lung cancer with brain metastases[J].Chin Cont Med Educat,2016,8(12):139-140.DOI:10.3969/j.issn.1674-9308.2016.12.100. [24] 徐靖.替莫唑胺联合全脑放疗治疗非小细胞肺癌脑转移瘤的疗效[J].中国实用医药,2016,11(20):150-151.DOI:10.14163/j.cnki.11-5547/r.2016.20.096. Xu J.Efficacy of Temozolomide Combined with whole brain radiotherapy in the treatment of non-small cell lung cancer with brain metastases[J].Chin Pract Med,2016,11(20):150-151.DOI:10.14163/j.cnki.11-5547/r.2016.20.096. [25] 赵世杰.替莫唑胺联合全脑放疗治疗非小细胞肺癌脑转移瘤的临床疗效[J].临床合理用药杂志,2016,9(6):102-103.DOI:10.15887/j.cnki.13-1389/r.2016.06.055. Zhao SJ.Clinical efficacy of Temozolomide combined with whole brain radiotherapy in the treatment of non-small cell lung cancer with brain metastases[J].J Clin Ration Drug Use,2016,9(6):102-103.DOI:10.15887/j.cnki.13-1389/r.2016.06.055. [26] 李耿.非小细胞肺癌脑转移者应用替莫唑胺联合全脑放疗的对照分析[J].医药前沿,2017,7(2):153-154.DOI:10.3969/j.issn.2095-1752.2017.02.129. Li G.Comparative analysis of temozolomide and whole brain radiotherapy in patients with non-small cell lung cancer with brain metastases[J].Health World,2017,7(2):153-154.DOI:10.3969/j.issn.2095-1752.2017.02.129. [27] 王宝红,郭守娟,张丹丹,等.替莫唑胺联合放疗治疗非小细胞肺癌脑转移的效果观察[J].河南医学研究,2017,26(18):3294-3296.DOI:10.3969/j.issn.1004-437X.2017.18.012 Wang BH,Guo BH,Zhang DD,et al. Effect of Temozolomide Combined with radiotherapy on non-small cell lung cancer with brain metastases[J].Henan Med Res,2017,26(18):3294-3296.DOI:10.3969/j.issn.1004-437X.2017.18.012. [28] 宋志雨.莫唑胺同步放疗治疗非小细胞肺癌脑转移瘤 40例临床观察[J].中国实用医药,2015,10(6):167-168.DOI:10.14163/j.cnki.11-5547/r.2015.06.114. Song ZY.Clinical observation of temozolomide concurrent radiotherapy for 40 cases of non-small cell lung cancer with brain metastases[J].Chin Pract Med,2015,10(06):167-168.DOI:10.14163/j.cnki.11-5547/r.2015.06.114. [29] Bailon O,Chouahnia K,Augier A,et al. Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma[J].Neuro Oncol,2012,14(4):491-495.DOI:10.1093/neuonc/nos004. [30] 程魏,张兰凤,肖娜,等.替莫唑胺联合全脑放疗治疗非小细胞肺癌脑转移疗效观察[J].河北医药,2013,35(15):2307-2308.DOI:10.3969/j.issn.1002-7386.2013.15.036. Cheng W,Zhang LF,Xiao N,et al. Clinical observation of Temozolomide Combined with whole brain radiotherapy in the treatment of non-small cell lung cancer with brain metastases[J].Hebei Med J,2013.35(15):2307-2308.DOI:10.3969/j.issn.1002-7386.2013.15.036 [31] 黄睿,张锡泉,杨小刚.吉非替尼联合全脑放疗与替莫唑胺联合全脑放疗治疗非小细胞肺癌脑转移的对比研究[J].实用中西医结合临床,2014,14(11):32-33.DOI:10.13638/j.issn.1671-4040.2014.11.019. Huang R,Zhang XQ,Yang XG.A comparative study of gefitinib combined with whole brain radiotherapy and Temozolomide Combined with whole brain radiotherapy for brain metastasis of non-small cell lung cancer[J].Clin Pract Integrat Tradit Chin West Med,2014.14(11):32-33.DOI:10.13638/j.issn.1671-4040.2014.11.019. [32] Niewald M,Berdel C,Fleckenstein J,et al. Toxicity after radiochemotherapy for glioblastoma using temozolomide—a retrospective evaluation[J].Radiat Oncol,2011,6(1):141.DOI:10.1186/1748-717X-6-141. [33] Armstrong TS,Cao Y,Scheurer ME,et al. Risk analysis of severe myelotoxicity with temozolomide:the effects of clinical and genetic factors[J].Neuro Oncol,2009,11(6):825-832.DOI:10.1215/15228517-2008-120. [34] Stupp R,Mason WP,van den Bent MJ,et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma[J].N Engl J Med,2005,352(10):987-996.DOI:10.1056/NEJMoa043330. [35] 程浩峰,何正文,任年军,等.替莫唑胺治疗胶质瘤不良反应的观察及分析[J].中外医疗,2014,33(16):32-33.DOI:10.3969/j.issn.1674-0742.2014.16.017. Cheng HF,He ZW,Ren NJ,et al. Observation and analysis of adverse reactions of temozolomide in the treatment of glioma[J].Chin Fore Med Treat,2014,33(16):32-33.DOI:10.3969/j.issn.1674-0742.2014.16.017. [36] Gu C,Lu J,Cui T,et al. Association between MGMT promoter methylation and non-small cell lung cancer:a meta-analysis[J].PLoS One,2013,8(9):601-605.DOI:10.1371/journal.pone.0072633. [37] Hashimoto K,Narita Y,Matsushita Y,et al. Methylation status of O6-methylguanine-DNA-methyl transferase promoter region in non-small-cell lung cancer patients with brain metastasis[J].Clin Transl Oncol,2012,14(1):31-35.DOI:10.1007/s12094-012-0758-6. [38] 李小芳,王悦,陈雪,等.替莫唑胺在MGMT高表达的非小细胞肺癌脑转移治疗中的应用观察[J].陕西医学杂志,2017,46(3):387-390.DOI:CNKI:SUN:SXYZ.0.2017-03-044. Li XF,Wang Y,Chen X,et al. Application of temozolomide in the treatment of brain metastasis of non-small cell lung cancer with high expression of MGMT[J].Shaanxi Med J,2017,46(3):387-390.DOI:CNKI:SUN:SXYZ.0.2017-03-044. [39] Addeo R,De Rosa C,Faiola V,et al. Phase 2 trial of temozolomide using protracted low-dose and whole-brain radiotherapy for nonsmall cell lung cancer and breast cancer patients with brain metastases[J].Cancer,2008,113(9):2524-2531.DOI:10.1002/cncr.23859. [40] Xin Y,Guo W,Yang CS,et al. Meta-analysis of whole-brain radiotherapy plus temozolomide compared with whole-brain radiotherapy for the treatment of brain metastases from non-small-cell lung cancer[J].Cancer Med,2018,7(4):981-990.DOI:10.1002/cam4.1306.