长期生存的胶质母细胞瘤患者临床特点及异柠檬酸脱氢酶1/2基因突变分析

Long-term survivors of glioblastoma: clinical features and IDH1/2 mutation analysis

目的探讨长期生存胶质母细胞瘤(GBM)患者的临床特点及与经典分子标记物异柠檬酸脱氢酶1/2基因(IDH1/2)突变的关系。方法对92例生存期达3年以上的原发性GBM病例进行回顾分析,分析指标包括患者的临床特征,治疗方式,分子标记物IDH1/2是否突变,总体生存期(OS)和无进展生存期(PFS)。结果进行手术治疗的新诊断GBM患者共368例,术后至少存活3年的GBM患者共92例(25%),平均(45.6±2.8)岁,KPS评分为(80±10)分。约1/2患者手术切除达到了T2/Flair像异常信号的全切除甚至脑叶的扩大切除(局限在非功能区的脑叶肿瘤),对于部分部位深在或者功能区、危险部位的肿瘤至少做到T1增强像的全切除。OS为3~8年,中位OS为54.6个月;1、3、5年的无进展生存率分别是89.5%、56.3%和48.2%。92例长期生存的GBM患者有84例肿瘤标本符合检测要求,其中IDH1/2突变型(IDH1/2+)有16例(16/84,19.0%),IDH1/2野生型有(IDH1/2-)68例(68/84,81.0%),但是在IDH1/2+组及IDH1/2-组之间OS和PFS均差异无统计学意义(P>0.05)。结论积极的手术切除是患者长期生存的必要条件,IDH1/2突变作为经典预后指标,在长期生存的GBM患者中并不适用。

Objective To describe the clinical characteristics of the GBM long - term survivors （LTS） with IDH1/2 mutations and investigate its association with overall survival （OS）. Methods Records of 92 newly diagnosed primary adult GBM patients who survived at least 36 months after operation were retrospectively reviewed. Descriptive sta- tistics of clinical characteristics, treatments received, and tumor biomarkers were reported. Estimates for progression - free survival （PFS） and overall survival （OS） were provided. Results In the 368 newly diagnosed adult GBM patients treated at a single institution from January 2009 to December 2010, 92 （25%） LTS GBM patients were identified, with a median age of 45.6 ±2. 8 years and a median preoperative Karnofsky Performance Score （KPS） of 80 ± 10. The surgical principle was resection of the parenchyma beyond the area of signal abnormalities on T2/FLAIR - weighted MRI （ known to be inva- ded by tumor cells） until eloquent structures were detected for non - eloquent tumors and the parenehyma of contrast en- hanced T1WI for eloquent or deep -sited tumors. The OS was 3 -8 years （median OS 5 years）. PFS rates at 12, 36, and 60 months were 89. 5% , 56. 3% , and 48.2% , respectively. Among the 84 GBM LTS with enough tumor samples for genetic testing, 16 （ 16/84, 17.4% ） had IDH1/2 mutations. No significant difference in median PFS or OS was found be- tween IDH1/2 mutated and wild -type patients. Conclusion Aggressive surgery is the basic guarantee for LTS in GBM patients. IDH1/2 status does not explain most of the long - term survivorship.