Mistry Akshitkumar M, Mummareddy Nishit, CreveCoeur Travis S, Lillard Jock C, Vaughn Brandy N, Gallant Jean-Nicolas, Hale Andrew T, Griffin Natalie, Wellons John C, Limbrick David D, Klimo Paul, Naftel Robert P
1Department of Neurological Surgery, Vanderbilt University Medical Center.
2School of Medicine, Vanderbilt University, Nashville, Tennessee.
J Neurosurg Pediatr. 2020 May 22;26(3):288-294. doi: 10.3171/2020.3.PEDS19593. Print 2020 Sep 1.
The subventricular zone (SVZ), housed in the lateral walls of the lateral ventricles, is the largest neurogenic niche in the brain. In adults, high-grade gliomas in contact or involved with the SVZ are associated with decreased survival. Whether this association holds true in the pediatric population remains unexplored. To address this gap in knowledge, the authors conducted this retrospective study in a pediatric population with high-grade gliomas treated at three comprehensive centers in the United States.
The authors retrospectively identified 63 patients, age ≤ 21 years, with supratentorial WHO grade III-IV gliomas treated at three academic centers. Basic demographic and clinical data regarding presenting signs and symptoms and common treatment variables were obtained. Preoperative MRI studies were evaluated to assess SVZ contact by tumor and to quantify tumor volume.
Sixty-three patients, including 34 males (54%), had a median age of 12.3 years (IQR 6.50-16.2) and a median tumor volume of 39.4 ml (IQR 19.4-65.8). Tumors contacting the SVZ (SVZ+) were noted in 34 patients (54%) and overall were larger than those not in contact with the SVZ (SVZ-; 51.1 vs 27.3, p = 0.002). The SVZ+ tumors were also associated with decreased survival. However, age, tumor volume, tumor grade, and treatment with chemotherapy and/or radiation were not associated with survival in the 63 patients. In the univariable analysis, near-total resection, gross-total resection, and seizure presentation were associated with increased survival (HR = 0.23, 95% CI 0.06-0.88, p = 0.03; HR = 0.26, 95% CI 0.09-0.74, p = 0.01; and HR = 0.46, 95% CI 0.22-0.97, p = 0.04, respectively). In a multivariable stepwise Cox regression analysis, only SVZ+ tumors remained significantly associated with decreased survival (HR = 1.94, 95% CI 1.03-3.64, p = 0.04).
High-grade glioma contact with the SVZ neural stem cell niche was associated with a significant decrease in survival in the pediatric population, as it is in the adult population. This result suggests that tumor contact with the SVZ is a general negative prognosticator in high-grade glioma independent of age group and invites biological investigations to understand the SVZ's role in glioma pathobiology.
脑室下区（SVZ）位于侧脑室侧壁，是大脑中最大的神经发生微环境。在成年人中，与SVZ接触或累及的高级别胶质瘤与生存率降低相关。这种关联在儿童群体中是否成立仍未得到探索。为填补这一知识空白，作者在美国三个综合中心对患有高级别胶质瘤的儿童群体进行了这项回顾性研究。
作者回顾性识别出63例年龄≤21岁、在三个学术中心接受幕上WHO III-IV级胶质瘤治疗的患者。获取了关于首发症状和体征以及常见治疗变量的基本人口统计学和临床数据。对术前MRI研究进行评估，以评估肿瘤与SVZ的接触情况并量化肿瘤体积。
63例患者中，包括34例男性（54%），中位年龄为12.3岁（四分位间距6.50 - 16.2），中位肿瘤体积为39.4 ml（四分位间距19.4 - 65.8）。34例患者（54%）的肿瘤与SVZ接触（SVZ+），总体上这些肿瘤比未与SVZ接触的肿瘤（SVZ-）更大（51.1 vs 27.3，p = 0.002）。SVZ+肿瘤也与生存率降低相关。然而，年龄、肿瘤体积、肿瘤分级以及化疗和/或放疗治疗与这63例患者的生存率无关。在单变量分析中，近全切除、全切除和癫痫发作表现与生存率增加相关（HR = 0.23，95% CI 0.06 - 0.88，p = 0.03；HR = 0.26，95% CI 0.09 - 0.74，p = 0.01；HR = 0.46，95% CI 0.22 - 0.97，p = 0.04）。在多变量逐步Cox回归分析中，只有SVZ+肿瘤仍与生存率降低显著相关（HR = 1.94，95% CI 1.03 - 3.64，p = 0.04）。
与成人一样，高级别胶质瘤与SVZ神经干细胞微环境接触与儿童群体的生存率显著降低相关。这一结果表明，肿瘤与SVZ接触是高级别胶质瘤中一个普遍的不良预后因素，与年龄组无关，并促使进行生物学研究以了解SVZ在胶质瘤病理生物学中的作用。
