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老年胶质母细胞瘤患者生存的预测因素以及短程(40 Gy)或标准疗程(60 Gy)放疗联合同步替莫唑胺的疗效:意大利神经肿瘤协会(AINO)的多中心回顾性研究

Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy) irradiation plus concomitant temozolomide in elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-Oncology).

作者信息

Lombardi Giuseppe, Pace Andrea, Pasqualetti Francesco, Rizzato Simona, Faedi Marina, Anghileri Elena, Nicolotto Elisa, Bazzoli Elena, Bellu Luisa, Villani Veronica, Fabi Alessandra, Ferrazza Patrizia, Gurrieri Lorena, Dall'Agata Monia, Eoli Marica, Della Puppa Alessandro, Pambuku Ardi, D'Avella Domenico, Berti Franco, Rudà Roberta, Zagonel Vittorina

机构信息

Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, via Gattamelata, 64, 35128, Padua, Italy.

Neuro-Oncology Unit, "Regina Elena" National Cancer Institute, Rome, Italy.

出版信息

J Neurooncol. 2015 Nov;125(2):359-67. doi: 10.1007/s11060-015-1923-x. Epub 2015 Sep 30.

Abstract

The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly patients with glioblastoma is unclear. We performed a large multicenter retrospective study to analyze prognostic factors and clinical outcome in these patients. Inclusion criteria were age ≥65 years, newly histologically confirmed glioblastoma, ECOG PS 0-2, adjuvant treatment with RT plus TMZ. We enrolled 237 patients; the average age was 71 and ECOG PS was 0-1 in 196 patients; gross total resection was performed in 174 cases. MGMT was analyzed in 151 persons and was methylated in 56 %. IDH1 was assessed in 100 patients and was mutated in 6 %. Seventy-one patients were treated with RT 40 Gy and 166 with RT 60 Gy. Progression-free survival and overall survival (OS) were 11.3 and 17.3 months, respectively. Overall survival was 19.4 vs 13.8 months for patients treated with RT 60 Gy and 40 Gy (p = 0.02); OS was 17.7 versus 16.1 months for patients treated with gross total resection vs partial surgery (p = 0.02); OS was 21.2 versus 13.6 months for methylated and unmethylated MGMT (p < 0.001). On multivariate analysis, gross total resection, RT 60 Gy, methylated MGMT and ECOG PS 0-1 were independent predictors of longer survival. Twenty-five patients (10 %) had grade 3-4 haematological toxicity during the concomitant treatment. We showed that, in elderly patients in good clinical condition treated with concomitant treatment, standard-course irradiation might be more effective than short-course irradiation. Methylated MGMT remains the most important prognostic factor.

摘要

替莫唑胺(TMZ)联合放射治疗(RT)对老年胶质母细胞瘤患者的疗效尚不清楚。我们进行了一项大型多中心回顾性研究,以分析这些患者的预后因素和临床结局。纳入标准为年龄≥65岁、新组织学确诊的胶质母细胞瘤、东部肿瘤协作组(ECOG)体能状态0-2、接受RT联合TMZ辅助治疗。我们纳入了237例患者;平均年龄为71岁,196例患者的ECOG体能状态为0-1;174例患者进行了全切除。对151例患者进行了O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)分析,其中56%呈甲基化。对100例患者进行了异柠檬酸脱氢酶1(IDH1)评估,其中6%发生了突变。71例患者接受40 Gy的RT治疗,166例患者接受60 Gy的RT治疗。无进展生存期和总生存期(OS)分别为11.3个月和17.3个月。接受60 Gy和40 Gy RT治疗的患者的总生存期分别为19.4个月和13.8个月(p = 0.02);接受全切除与部分切除手术的患者的OS分别为17.7个月和16.1个月(p = 0.02);MGMT甲基化和未甲基化的患者的OS分别为21.2个月和13.6个月(p < 0.001)。多因素分析显示,全切除、60 Gy的RT、MGMT甲基化和ECOG体能状态0-1是生存期延长的独立预测因素。25例患者(10%)在同步治疗期间发生了3-4级血液学毒性。我们发现,在接受同步治疗的临床状况良好的老年患者中,标准疗程放疗可能比短疗程放疗更有效。MGMT甲基化仍然是最重要的预后因素。

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