Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland, USA.
Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):616-22. doi: 10.1016/j.ijrobp.2013.02.014. Epub 2013 Mar 26.
Neural progenitor cells in the subventricular zone (SVZ) have a controversial role in glioblastoma multiforme (GBM) as potential tumor-initiating cells. The purpose of this study was to examine the relationship between radiation dose to the SVZ and survival in GBM patients.
The study included 116 patients with primary GBM treated at the Johns Hopkins Hospital between 2006 and 2009. All patients underwent surgical resection followed by adjuvant radiation therapy with intensity modulated radiation therapy (60 Gy/30 fractions) and concomitant temozolomide. Ipsilateral, contralateral, and bilateral SVZs were contoured on treatment plans by use of coregistered magnetic resonance imaging and computed tomography. Multivariate Cox regression was used to examine the relationship between mean SVZ dose and progression-free survival (PFS), as well as overall survival (OS). Age, Karnofsky Performance Status score, and extent of resection were used as covariates. The median age was 58 years (range, 29-80 years).
Of the patients, 12% underwent biopsy, 53% had subtotal resection (STR), and 35% had gross total resection (GTR). The Karnofsky Performance Status score was less than 90 in 54 patients and was 90 or greater in 62 patients. The median ipsilateral, contralateral, and bilateral mean SVZ doses were 48.7 Gy, 34.4 Gy, and 41.5 Gy, respectively. Among patients who underwent GTR, a mean ipsilateral SVZ dose of 40 Gy or greater was associated with a significantly improved PFS compared with patients who received less than 40 Gy (15.1 months vs 10.3 months; P=.028; hazard ratio, 0.385 [95% confidence interval, 0.165-0.901]) but not in patients undergoing STR or biopsy. The subgroup of GTR patients who received an ipsilateral dose of 40 Gy or greater also had a significantly improved OS (17.5 months vs 15.6 months; P=.027; hazard ratio, 0.385 [95% confidence interval, 0.165-0.895]). No association was found between SVZ radiation dose and PFS and OS among patients who underwent STR or biopsy.
A mean radiation dose of 40 Gy or greater to the ipsilateral SVZ was associated with a significantly improved PFS and OS in patients with GBM after GTR.
脑室下区（SVZ）中的神经祖细胞在多形性胶质母细胞瘤（GBM）中作为潜在的肿瘤起始细胞具有争议性的作用。本研究的目的是检查 SVZ 放射剂量与 GBM 患者生存之间的关系。
这项研究包括了 2006 年至 2009 年在约翰霍普金斯医院接受治疗的 116 名原发性 GBM 患者。所有患者均接受手术切除，随后接受强度调制放射治疗（60Gy/30 次分割）和同时服用替莫唑胺。通过使用磁共振成像和计算机断层扫描的配准，在治疗计划中描绘同侧、对侧和双侧 SVZ。使用多变量 Cox 回归来检查平均 SVZ 剂量与无进展生存期（PFS）以及总生存期（OS）之间的关系。年龄、卡诺夫斯基表现状态评分和切除范围用作协变量。中位年龄为 58 岁（范围，29-80 岁）。
在患者中，12%进行了活检，53%进行了次全切除术（STR），35%进行了大体全切除术（GTR）。54 名患者的卡诺夫斯基表现状态评分为小于 90，62 名患者的卡诺夫斯基表现状态评分为 90 或更高。同侧、对侧和双侧平均 SVZ 剂量分别为 48.7Gy、34.4Gy 和 41.5Gy。在接受 GTR 的患者中，与接受小于 40Gy 的患者相比，接受 40Gy 或更高剂量的同侧 SVZ 治疗与显著改善的 PFS 相关（15.1 个月比 10.3 个月；P=.028；风险比，0.385[95%置信区间，0.165-0.901]），但在接受 STR 或活检的患者中并非如此。接受同侧剂量为 40Gy 或更高的 GTR 患者亚组的 OS 也显著改善（17.5 个月比 15.6 个月；P=.027；风险比，0.385[95%置信区间，0.165-0.895]）。在接受 STR 或活检的患者中，SVZ 放射剂量与 PFS 和 OS 之间没有关联。
GBM 患者接受 GTR 后，同侧 SVZ 的平均放射剂量为 40Gy 或更高，与 PFS 和 OS 的显著改善相关。
