高辐射剂量对异柠檬酸脱氢酶野生型胶质母细胞瘤群体中神经干细胞龛的负面生存影响。
Negative Survival Impact of High Radiation Doses to Neural Stem Cells Niches in an IDH-Wild-Type Glioblastoma Population.
作者信息
Muracciole Xavier, El-Amine Wassim, Tabouret Emmeline, Boucekine Mohamed, Barlier Anne, Petrirena Gregorio, Harivony Tovo, Solignac Laetitia, Chinot Olivier L, Macagno Nicolas, Figarella-Branger Dominique, Padovani Laetitia
机构信息
Radiotherapy Department, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
Neuro-Oncology Department, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
出版信息
Front Oncol. 2018 Oct 4;8:426. doi: 10.3389/fonc.2018.00426. eCollection 2018.
Assess the impact of radiation doses to neural stem cell (NSC) niches in patients with IDH-wild-type glioblastoma. Fifty patients were included in the study. NSC niches [SubVentricular Zone (SVZ) and Sub Granular Zone (SGZ)] were contoured by fusing CT scans and pre-therapy MRI, Tumor location defined ipsilateral and contralateral SVZ and SGZ. Prognostic significance of clinical, biological and dosimetric parameters were examined. We generated a Recursive Partitioning Analysis (RPA) model with independent prognostic classes. Median follow-up: 23.8 months. Event free and overall survival (OS): 10 and 19.1 months. Incomplete surgery, PTV (planning target volume), ipsilateral SVZ or NSC niche mean dose > 57.4 Gy, contralateral NSC niche mean dose > 35 Gy and bilateral NSC niche mean dose > 44 Gy were significantly correlated with reduced OS. Only EGFR amplification was an independent prognostic factor ( = 0.019) for OS. RPA generated independent risk groups: 1 (low risk): [ipsilateral NSC mean dose (INMD) < 58.01 Gy and methylated MGMT promoter], 2: (INMD < 58.01 Gy and unmethylated MGMT promoter and contralateral SVZ mean dose < 18.6 Gy; = 0.43), 3: (INMD < 58.01 Gy and unmethylated MGMT promoter and contralateral SVZ mean dose > 18.6 Gy; = 0.002) and 4: (very high risk) (INMD > 58.01 Gy; < 0.001). High radiation doses to ipsilateral NSC and contralateral SVZ could have a negative impact on overall survival in IDH-wild-type glioblastoma population.
评估异柠檬酸脱氢酶（IDH）野生型胶质母细胞瘤患者神经干细胞（NSC）微环境所受辐射剂量的影响。本研究纳入了50例患者。通过融合CT扫描和治疗前MRI勾勒出NSC微环境[脑室下区（SVZ）和颗粒下区（SGZ）]，肿瘤位置确定同侧和对侧的SVZ和SGZ。研究了临床、生物学和剂量学参数的预后意义。我们生成了具有独立预后类别的递归分割分析（RPA）模型。中位随访时间：23.8个月。无事件生存期和总生存期（OS）分别为10个月和l9.1个月。手术未完全切除、计划靶体积（PTV）、同侧SVZ或NSC微环境平均剂量>57.4 Gy、对侧NSC微环境平均剂量>35 Gy以及双侧NSC微环境平均剂量>44 Gy均与OS降低显著相关。只有表皮生长因子受体（EGFR）扩增是OS的独立预后因素（P = 0.019）。RPA生成了独立风险组：1组（低风险）：[同侧NSC平均剂量（INMD）<58.01 Gy且O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化]，2组：（INMD<58.01 Gy且MGMT启动子未甲基化且对侧SVZ平均剂量<18.6 Gy；P = 0.43），3组：（INMD<58.01 Gy且MGMT启动子未甲基化且对侧SVZ平均剂量>18.6 Gy；P = 0.002）和4组（极高风险）（INMD>58.01 Gy；P<0.001）。同侧NSC和对侧SVZ接受高辐射剂量可能会对IDH野生型胶质母细胞瘤患者的总生存期产生负面影响。
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