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
Radiotherapy Department, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
Neuro-Oncology Department, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
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。
