高分级脑胶质瘤综合治疗的徇证医学研究进展(2)
5 化疗
GMT(Glioma Meta nanlysis Trislists)Group[4]对随机分组的3004例高分级脑胶质瘤患者进行荟萃分析(I类证据),发现术后放化疗组较单纯放疗组生存时间明显延长(化疗多采用环乙亚硝脲类药物口服或静脉滴注),相对危险度为0.85(95%可信区间0.78~0.91,P<0.0001),死亡风险下降15%。故主张脑胶质瘤的综合治疗应包括化疗(推荐级别:A级)。Lo nardi等[17]研究(3类证据)认为Temozolomide(TMZ)对提高复发高分级胶质瘤的生存率有统计学意义,毒副反应相对亚硝酸脲为主的化疗方案要小,是一种新型的、有前途的化疗药(推荐级别:C级)。
6 皮质类固醇激素的使用
自从Galicich等于1961年报道皮质类固醇激素可减轻脑瘤患者的脑水肿从而降低颅内压,激素很快被广泛应用于各种脑瘤,其中地塞米松最常用。从开始用药、减量到停药都是依靠以往的经验。在为数不多的随机分组研究中,Vecht等报道脑转移瘤的治疗时使用低剂量激素(4 mg)和高剂量(16 mg)的差别,结果发现高剂量组一般从用药28d后减量,引起近端肢体肌病(38%)和柯兴氏综合征(65%)。不仅如此,滥用激素还会混淆症状,导致临床试验的误判[18]。临床亟待更为科学的前瞻性研究结果来代替这种经验式的治疗方法。
, http://www.100md.com
7 结论
高分化脑胶质瘤的大宗前瞻性研究的目的是如何缓解症状和提高患者生活质量,并非每项临床试验结果都要来自1类数据。就目前(3~4类数据)研究情况来看,对于大多数预后不良的高分级脑胶质瘤,我们建议首程尽量完全切除和术后短程放疗作为标准的前期和治疗方法。而多疗程的化疗作为后续的治疗手段,程序的多少要根据患者的身体状况而定,而对其他少数患者(存活时间>3个月),可实施临终关怀。
参考文献
[1] 张纪,深入开展胶质瘤综合治疗及其基础研究.中华神经外科杂志,2003,19(1):1 2.
[2] 殷蔚伯,谷铣之.肿瘤放射治疗学.中国协和医科大学出版社,2002:1018 1022.
[3] Gupta T, Sarin R. Poor prognosis high grade gliomas: evolingan evidence based standard of care.Lancet,2002,3(9):557 564.
, 百拇医药
[4] Stewart L A. Chemotherapy in adult high grade gliomas: a systematic review and meta analysis of individual patient data from 12 randommised trals.Lancet,2002,359(9311):1011 1018.
[5] 贾红英,王洁贞,赵敬杰.神经胶质瘤术后预后因素的研究.中华流行病学杂志,2003,24(3):229 232.
[6] Do V,Gebski V,Barten M B. The effect of waiting for radiotherapy for grade Ⅲ/Ⅳ gliomas. Radiother Oncol, 2007, 57(4):131 136.
[7] Pirzkall A,Nelson S J, McKnight T R,et al. Metabolic I magining of lowgrade gliomas with three dimensional magnetic resonance spectroscopy.Int J Radiat Oncol Biol Phys,2002,53(5):1254 1264.
, http://www.100md.com
[8] Nariai T, Tanaka Y, Wakimoto H, et al.Usefulness ofL [methyl11C] methionine positron emission tomography as a biological motitoring tool in the treatment of glioma. J Neurosurg, 2005; 103(3): 498 507.
[9] Glinski B. Postoperative hypofractionated radiotherapy versusconventionally fractionated radiotherapy in m alignant gliomas: a preliminary report on a randomized trial . Radiother Oncol, 2003,67(2):167 172.
[10] McAleese J J, Stenning S P, Ashley S, et al. Hypofractionated radiotherapy for poor prognosis m alignant glioma: matched pairsurvival analysis with MRC controls . Radiother Oncol, 2003; 67(2): 177 182.
, 百拇医药
[11] Kleinberg L, Slick T, Enger C, et al. Short courseradiotherapyis an appropriate option for most m alignant glioma patients.Int J Radiat Oncol Biol Phys,1997,38(1):31 36.
[12] Hoegler D B, Davey P.A prodpective study of short courseradiotherapy in the elderly patients with m alignant glioma. JNeurooncol, 1997,33(3):201 204.
[13] Ford J M, Stenning S P, Boote D J, et al. A short fractionation radiotherapy for poor prognosis patients with highgrade glioma .Clin Oncol,1997,9(1):20 24.
, 百拇医药
[14] Jeremic B,Shabamoto Y, Grujicic D, et al. Short course radiotherapy in elderly and frail patients with glioblastoma multiforme: a phase II study. Neurooncol, 1999,44(1):85 90.
[15] Hulshof M C, Schimmel E C, Andries Bosch D, et al. Hypofractionation in glioblastoma multiforme. Radiother Oncol,2000,54(2):143 148.
[16] Nieder C,Andratschke N, Wiedenmann N, et al. Radiotherapy for highgrade gliomas. Does altered fractionation improve theoutcome Strahlenther Onkol,2004,180(7):401 407.
, http://www.100md.com
[17] Lonardi S, Tosoni A, Brandes A A, et al. Adjuvant chemother apy in the treatment of high grade gliomas. Cancer TreatRev,2005,31(2):79 89.
[18] Sarin R, DinshawK A. Final results of the Royal College of Radiologist`trial comparing two different radiotherapy schedulesin the treatment of cerebral metastases.Clin Oncol(R CollRadiol),1997,9(4):272., http://www.100md.com(孙高令 王同新 白云安)
GMT(Glioma Meta nanlysis Trislists)Group[4]对随机分组的3004例高分级脑胶质瘤患者进行荟萃分析(I类证据),发现术后放化疗组较单纯放疗组生存时间明显延长(化疗多采用环乙亚硝脲类药物口服或静脉滴注),相对危险度为0.85(95%可信区间0.78~0.91,P<0.0001),死亡风险下降15%。故主张脑胶质瘤的综合治疗应包括化疗(推荐级别:A级)。Lo nardi等[17]研究(3类证据)认为Temozolomide(TMZ)对提高复发高分级胶质瘤的生存率有统计学意义,毒副反应相对亚硝酸脲为主的化疗方案要小,是一种新型的、有前途的化疗药(推荐级别:C级)。
6 皮质类固醇激素的使用
自从Galicich等于1961年报道皮质类固醇激素可减轻脑瘤患者的脑水肿从而降低颅内压,激素很快被广泛应用于各种脑瘤,其中地塞米松最常用。从开始用药、减量到停药都是依靠以往的经验。在为数不多的随机分组研究中,Vecht等报道脑转移瘤的治疗时使用低剂量激素(4 mg)和高剂量(16 mg)的差别,结果发现高剂量组一般从用药28d后减量,引起近端肢体肌病(38%)和柯兴氏综合征(65%)。不仅如此,滥用激素还会混淆症状,导致临床试验的误判[18]。临床亟待更为科学的前瞻性研究结果来代替这种经验式的治疗方法。
, http://www.100md.com
7 结论
高分化脑胶质瘤的大宗前瞻性研究的目的是如何缓解症状和提高患者生活质量,并非每项临床试验结果都要来自1类数据。就目前(3~4类数据)研究情况来看,对于大多数预后不良的高分级脑胶质瘤,我们建议首程尽量完全切除和术后短程放疗作为标准的前期和治疗方法。而多疗程的化疗作为后续的治疗手段,程序的多少要根据患者的身体状况而定,而对其他少数患者(存活时间>3个月),可实施临终关怀。
参考文献
[1] 张纪,深入开展胶质瘤综合治疗及其基础研究.中华神经外科杂志,2003,19(1):1 2.
[2] 殷蔚伯,谷铣之.肿瘤放射治疗学.中国协和医科大学出版社,2002:1018 1022.
[3] Gupta T, Sarin R. Poor prognosis high grade gliomas: evolingan evidence based standard of care.Lancet,2002,3(9):557 564.
, 百拇医药
[4] Stewart L A. Chemotherapy in adult high grade gliomas: a systematic review and meta analysis of individual patient data from 12 randommised trals.Lancet,2002,359(9311):1011 1018.
[5] 贾红英,王洁贞,赵敬杰.神经胶质瘤术后预后因素的研究.中华流行病学杂志,2003,24(3):229 232.
[6] Do V,Gebski V,Barten M B. The effect of waiting for radiotherapy for grade Ⅲ/Ⅳ gliomas. Radiother Oncol, 2007, 57(4):131 136.
[7] Pirzkall A,Nelson S J, McKnight T R,et al. Metabolic I magining of lowgrade gliomas with three dimensional magnetic resonance spectroscopy.Int J Radiat Oncol Biol Phys,2002,53(5):1254 1264.
, http://www.100md.com
[8] Nariai T, Tanaka Y, Wakimoto H, et al.Usefulness ofL [methyl11C] methionine positron emission tomography as a biological motitoring tool in the treatment of glioma. J Neurosurg, 2005; 103(3): 498 507.
[9] Glinski B. Postoperative hypofractionated radiotherapy versusconventionally fractionated radiotherapy in m alignant gliomas: a preliminary report on a randomized trial . Radiother Oncol, 2003,67(2):167 172.
[10] McAleese J J, Stenning S P, Ashley S, et al. Hypofractionated radiotherapy for poor prognosis m alignant glioma: matched pairsurvival analysis with MRC controls . Radiother Oncol, 2003; 67(2): 177 182.
, 百拇医药
[11] Kleinberg L, Slick T, Enger C, et al. Short courseradiotherapyis an appropriate option for most m alignant glioma patients.Int J Radiat Oncol Biol Phys,1997,38(1):31 36.
[12] Hoegler D B, Davey P.A prodpective study of short courseradiotherapy in the elderly patients with m alignant glioma. JNeurooncol, 1997,33(3):201 204.
[13] Ford J M, Stenning S P, Boote D J, et al. A short fractionation radiotherapy for poor prognosis patients with highgrade glioma .Clin Oncol,1997,9(1):20 24.
, 百拇医药
[14] Jeremic B,Shabamoto Y, Grujicic D, et al. Short course radiotherapy in elderly and frail patients with glioblastoma multiforme: a phase II study. Neurooncol, 1999,44(1):85 90.
[15] Hulshof M C, Schimmel E C, Andries Bosch D, et al. Hypofractionation in glioblastoma multiforme. Radiother Oncol,2000,54(2):143 148.
[16] Nieder C,Andratschke N, Wiedenmann N, et al. Radiotherapy for highgrade gliomas. Does altered fractionation improve theoutcome Strahlenther Onkol,2004,180(7):401 407.
, http://www.100md.com
[17] Lonardi S, Tosoni A, Brandes A A, et al. Adjuvant chemother apy in the treatment of high grade gliomas. Cancer TreatRev,2005,31(2):79 89.
[18] Sarin R, DinshawK A. Final results of the Royal College of Radiologist`trial comparing two different radiotherapy schedulesin the treatment of cerebral metastases.Clin Oncol(R CollRadiol),1997,9(4):272., http://www.100md.com(孙高令 王同新 白云安)