高龄胶质母细胞瘤患者术后放化疗效果的系统评价
|
摘要
(1)目的评价单独标准剂量放疗、大分割放疗、替莫唑胺治疗及两种放疗方案结合替莫唑胺治疗在高龄胶质母细胞瘤患者中的有效性及安全性。(2)方法采用Cochrane系统评价的方法,检索Pubmed、Medline、Cochrane library及OVID各数据库;按照试验设计进行文献筛选及质量评估,提取数据后进行meta分析。(3)结果纳入的研究中总生存期分析:单独大分割放疗对比单独标准放疗、单独替莫唑胺对比单独标准放疗组和替莫唑胺结合大分割放疗对比替莫唑胺结合标准放疗组差异均无统计学意义(P值均>0.05)。替莫唑胺治疗中MGMT启动子甲基化对比非甲基化差异有统计学意义(P <0.05),揭示MGMT启动子甲基化与非甲基化相比显著延长了患者的生存期;在副作用方面标准放疗对比大分割放疗的副作用事件发生率差异无统计学意义(P=0.49),而替莫唑胺对比放疗的3～4级血液毒性反应明显增加。(4)结论本研究证实在高龄胶质母细胞瘤患者中MGMT启动子甲基化状态下选择替莫唑胺治疗更合理、获益更大,但替莫唑胺治疗比放疗的血液毒性反应发生率高。
Objective To evaluate the safety and efficacy of the treatment of alone standard radiotherapy,hypofractionated radiotherapy and temozolomide,and the two types of radiotherapy combined temozolomide in olderly patients with glioblastoma.Methods Using the method of Cochrane's system evaluation to search Pubmed,Cochrane library,Medline and OVID databases;and then according to the design of experiment for selection and evaluation the quality of literature,finally after extract the data for meta-analysis.Results Included in the study,the group of the alone of hypofractionated radiotherapy or temozolomide compared with the alone of standard radiotherapy,and the group of temozolomide combined with hypofractionated radiotherapy compared with temozolomide combined with standard radiotherapy respectively showed that:there were no statistical significance(P >0.05).In the treatment of temozolomide:the methylation of MGMT promoter compared with the non-methylation showed that there was statistical significance(P <0.05).In the aspect of side effects showed that standard radiotherapy versus hypofractionated radiotherapy had no difference(P =0.49),however the grade 3～4of hematotoxicity is increasing remarkly in the group of temozolomide versus radiotherapy.ConclusionThis study showed that treatment of temozolomide had more benefit in the elderly glioblastoma patient with the methylation of MGMT prompter,but using the temozolomide had more hematotoxicity than radiotherapy.
Objective To evaluate the safety and efficacy of the treatment of alone standard radiotherapy,hypofractionated radiotherapy and temozolomide,and the two types of radiotherapy combined temozolomide in olderly patients with glioblastoma.Methods Using the method of Cochrane's system evaluation to search Pubmed,Cochrane library,Medline and OVID databases;and then according to the design of experiment for selection and evaluation the quality of literature,finally after extract the data for meta-analysis.Results Included in the study,the group of the alone of hypofractionated radiotherapy or temozolomide compared with the alone of standard radiotherapy,and the group of temozolomide combined with hypofractionated radiotherapy compared with temozolomide combined with standard radiotherapy respectively showed that:there were no statistical significance(P >0.05).In the treatment of temozolomide:the methylation of MGMT promoter compared with the non-methylation showed that there was statistical significance(P <0.05).In the aspect of side effects showed that standard radiotherapy versus hypofractionated radiotherapy had no difference(P =0.49),however the grade 3～4of hematotoxicity is increasing remarkly in the group of temozolomide versus radiotherapy.ConclusionThis study showed that treatment of temozolomide had more benefit in the elderly glioblastoma patient with the methylation of MGMT prompter,but using the temozolomide had more hematotoxicity than radiotherapy.
引文
[1]Franceschi E,Depenni R,Paccapelo A,et al.Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide?A PERNO prospective study[J].J Neurooncol,2016,128(1):157-62
[2]Fariselli L,Pinzi V,Milanesi I,et al.Shortcourse radiotherapy in elderly patients with glioblastoma:feasibility and efficacy of results from a single centre[J].Strahlenther Onkol,2013,189(6):456-61
[3] Arvold ND,Reardon DA.Treatment options and outcomes for glioblastoma in the elderly patient[J].Clin Interv Aging,2014,21(9):357-67
[4]Fiorentino A,De Bonis P,Chiesa S.Elderly patients with glioblastoma:the treatment challenge[J].Expert Rev Neurother,2013,13(10):1099-105
[5]Tabouret E,Tassy L,Chinot O.High-grade glioma in elderly patients:can the oncogeriatrician help?[J].Clin Interv Aging,2013,11(8):1617-24
[6] Malmstr9m A,Grnberg BH,Marosi C,et al.Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60years with glioblastoma:the Nordic randomised,phase 3trial[J].Lancet Oncol,2012,13(9):916-26
[7]Glantz M,Chamberlain M,Liu Q,et al.Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas[J].Cancer,2003,97(9):2262-6
[8]Roa W,Brasher PM,Bauman G,et al.Abbreviated course of radiation therapy in older patients with glioblastoma multiforme:aprospective randomized clinical trial[J].J Clin Oncol,2004,22(9):1583-8
[9]Wick W,Platten M,Meisner C,et al.Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly:the NOA-08randomised,phase 3trial[J].Lancet Oncol,2012,13(7):707-15
[10]Minniti G,Scaringi C,Lanzetta G,et al.Standard(60Gy)or short-course(40Gy)irradiation plus concomitant and adjuvant temozolomide for elderly patients with glioblastoma:a propensity-matched analysis[J].Int J Radiat Oncol Biol Phys,2015,91(1):109-15
[11]Lombardi G,Pace A,Pasqualetti F,et al.Predictors of survival and effect of short(40Gy)or standard-course(60Gy)irradiation plus concomitant temozolomide in elderly patients with glioblastoma:a multicenter retrospective study of AINO(Italian Association of Neuro-Oncology)[J].J Neurooncol,2015,125(2):359-67
[12]Fiorica F,Berretta M,Colosimo C,et al.Glioblastoma in elderly patients:safety and efficacy of adjuvant radiotherapy with concomitant temozolomide[J].Arch Gerontol Geriatr,2010,51(1):31-5
[13]Cao JQ,Fisher BJ,Bauman GS,et al.Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme:a review of ten-year single institutional experience[J].J Neurooncol,2012,107(2):395-405
[14]Keime-Guibert F,Chinot O,Taillandier L,et al.Radiotherapy for glioblastoma in the elderly[J].N Engl J Med,2007,356(15):1527-35
[15]Jeremic B,Shibamoto Y,Grujicic D,et al.Shortcourse radiotherapy in elderly and frail patients with glioblastoma multiforme[J].A phase II study.J Neurooncol,1999,44(1):85-90
[16] Chinot OL.Should radiotherapy be standard therapy for brain tumors in the elderly?[J].Cons.Semin Oncol,2003,30(6Suppl 19):68-71
[17]Chakravarti A,Erkkinen MG,Nestler U,et al.Temozolomide-mediatedradiationenhancement in glioblastoma:a report on underlying mechanisms[J].Clin Cancer Res,2006,12(15):4738-46
[18]Stupp R,Mason WP,van den Bent MJ,et al.European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups;National Cancer Institute of Canada Clinical Trials Group.Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma[J].N Engl J Med,2005,352(10):987-96
[19]Hegi ME,Liu L,Herman JG,et al.Correlation of O6-methylguanine methyltransferase(MGMT)promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity[J].J Clin Oncol,2008,26(25):4189-99
[2]Fariselli L,Pinzi V,Milanesi I,et al.Shortcourse radiotherapy in elderly patients with glioblastoma:feasibility and efficacy of results from a single centre[J].Strahlenther Onkol,2013,189(6):456-61
[3] Arvold ND,Reardon DA.Treatment options and outcomes for glioblastoma in the elderly patient[J].Clin Interv Aging,2014,21(9):357-67
[4]Fiorentino A,De Bonis P,Chiesa S.Elderly patients with glioblastoma:the treatment challenge[J].Expert Rev Neurother,2013,13(10):1099-105
[5]Tabouret E,Tassy L,Chinot O.High-grade glioma in elderly patients:can the oncogeriatrician help?[J].Clin Interv Aging,2013,11(8):1617-24
[6] Malmstr9m A,Grnberg BH,Marosi C,et al.Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60years with glioblastoma:the Nordic randomised,phase 3trial[J].Lancet Oncol,2012,13(9):916-26
[7]Glantz M,Chamberlain M,Liu Q,et al.Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas[J].Cancer,2003,97(9):2262-6
[8]Roa W,Brasher PM,Bauman G,et al.Abbreviated course of radiation therapy in older patients with glioblastoma multiforme:aprospective randomized clinical trial[J].J Clin Oncol,2004,22(9):1583-8
[9]Wick W,Platten M,Meisner C,et al.Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly:the NOA-08randomised,phase 3trial[J].Lancet Oncol,2012,13(7):707-15
[10]Minniti G,Scaringi C,Lanzetta G,et al.Standard(60Gy)or short-course(40Gy)irradiation plus concomitant and adjuvant temozolomide for elderly patients with glioblastoma:a propensity-matched analysis[J].Int J Radiat Oncol Biol Phys,2015,91(1):109-15
[11]Lombardi G,Pace A,Pasqualetti F,et al.Predictors of survival and effect of short(40Gy)or standard-course(60Gy)irradiation plus concomitant temozolomide in elderly patients with glioblastoma:a multicenter retrospective study of AINO(Italian Association of Neuro-Oncology)[J].J Neurooncol,2015,125(2):359-67
[12]Fiorica F,Berretta M,Colosimo C,et al.Glioblastoma in elderly patients:safety and efficacy of adjuvant radiotherapy with concomitant temozolomide[J].Arch Gerontol Geriatr,2010,51(1):31-5
[13]Cao JQ,Fisher BJ,Bauman GS,et al.Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme:a review of ten-year single institutional experience[J].J Neurooncol,2012,107(2):395-405
[14]Keime-Guibert F,Chinot O,Taillandier L,et al.Radiotherapy for glioblastoma in the elderly[J].N Engl J Med,2007,356(15):1527-35
[15]Jeremic B,Shibamoto Y,Grujicic D,et al.Shortcourse radiotherapy in elderly and frail patients with glioblastoma multiforme[J].A phase II study.J Neurooncol,1999,44(1):85-90
[16] Chinot OL.Should radiotherapy be standard therapy for brain tumors in the elderly?[J].Cons.Semin Oncol,2003,30(6Suppl 19):68-71
[17]Chakravarti A,Erkkinen MG,Nestler U,et al.Temozolomide-mediatedradiationenhancement in glioblastoma:a report on underlying mechanisms[J].Clin Cancer Res,2006,12(15):4738-46
[18]Stupp R,Mason WP,van den Bent MJ,et al.European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups;National Cancer Institute of Canada Clinical Trials Group.Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma[J].N Engl J Med,2005,352(10):987-96
[19]Hegi ME,Liu L,Herman JG,et al.Correlation of O6-methylguanine methyltransferase(MGMT)promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity[J].J Clin Oncol,2008,26(25):4189-99