Clinica Neurologica, Department of Neuroscience, University of Padova, Padova, Italy.
Padova Neuroscience Center, University of Padova, Padova, Italy.
JAMA Neurol. 2023 Nov 1;80(11):1222-1231. doi: 10.1001/jamaneurol.2023.3284.
The prognosis of overall survival (OS) in patients with glioblastoma (GBM) may depend on the underlying structural connectivity of the brain.
To examine the association between white matter tracts affected by GBM and patients' OS by means of a new tract density index (TDI).
DESIGN, SETTING, AND PARTICIPANTS: This prognostic study in patients with a histopathologic diagnosis of GBM examined a discovery cohort of 112 patients who underwent surgery between February 1, 2015, and November 30, 2020 (follow-up to May 31, 2023), in Italy and 70 patients in a replicative cohort (n = 70) who underwent surgery between September 1, 2012, and November 30, 2015 (follow-up to May 31, 2023), in Germany. Statistical analyses were performed from June 1, 2021, to May 31, 2023. Thirteen and 12 patients were excluded from the discovery and the replicative sets, respectively, because of magnetic resonance imaging artifacts.
The density of white matter tracts encompassing GBM.
Correlation, linear regression, Cox proportional hazards regression, Kaplan-Meier, and prediction analysis were used to assess the association between the TDI and OS. Results were compared with common prognostic factors of GBM, including age, performance status, O6-methylguanine-DNA methyltransferase methylation, and extent of surgery.
In the discovery cohort (n = 99; mean [SD] age, 62.2 [11.5] years; 29 female [29.3%]; 70 male [70.7%]), the TDI was significantly correlated with OS (r = -0.34; P < .001). This association was more stable compared with other prognostic factors. The TDI showed a significant regression pattern (Cox: hazard ratio, 0.28 [95% CI, 0.02-0.55; P = .04]; linear: t = -2.366; P = .02). and a significant Kaplan-Meier stratification of patients as having lower or higher OS based on the TDI (log-rank test = 4.52; P = .03). Results were confirmed in the replicative cohort (n = 58; mean [SD] age, 58.5 [11.1] years, 14 female [24.1%]; 44 male [75.9%]). High (24-month cutoff) and low (18-month cutoff) OS was predicted based on the TDI computed in the discovery cohort (accuracy = 87%).
In this study, GBMs encompassing regions with low white matter tract density were associated with longer OS. These findings indicate that the TDI is a reliable presurgical outcome predictor that may be considered in clinical trials and clinical practice. These findings support a framework in which the outcome of GBM depends on the patient's brain organization.
胶质母细胞瘤（GBM）患者的总生存（OS）预后可能取决于大脑的基础结构连通性。
通过一种新的白质束密度指数（TDI），研究受 GBM 影响的白质束与患者 OS 之间的关联。
设计、地点和参与者：这项在经组织病理学诊断为 GBM 的患者中进行的预后研究，纳入了意大利 112 名患者的发现队列（2015 年 2 月 1 日至 2020 年 11 月 30 日接受手术，随访至 2023 年 5 月 31 日）和德国的 70 名复制队列患者（n=70，于 2012 年 9 月 1 日至 2015 年 11 月 30 日接受手术，随访至 2023 年 5 月 31 日）。统计分析于 2021 年 6 月 1 日至 2023 年 5 月 31 日进行。由于磁共振成像伪影，分别有 13 名和 12 名患者被排除在发现组和复制组之外。
GBM 累及的白质束密度。
采用相关性、线性回归、Cox 比例风险回归、Kaplan-Meier 分析和预测分析来评估 TDI 与 OS 之间的关联。结果与 GBM 的常见预后因素（包括年龄、表现状态、O6-甲基鸟嘌呤-DNA 甲基转移酶甲基化和手术范围）进行了比较。
在发现队列（n=99；平均[SD]年龄 62.2[11.5]岁；女性 29 例[29.3%]；男性 70 例[70.7%]）中，TDI 与 OS 显著相关（r=-0.34；P<0.001）。与其他预后因素相比，这种关联更加稳定。TDI 显示出显著的回归模式（Cox：危险比，0.28[95%CI，0.02-0.55；P=0.04]；线性：t=-2.366；P=0.02），并根据 TDI 对患者进行了显著的 Kaplan-Meier 分层，低或高 OS（对数秩检验=4.52；P=0.03）。结果在复制队列（n=58；平均[SD]年龄 58.5[11.1]岁，女性 14 例[24.1%]；男性 44 例[75.9%]）中得到了证实。基于在发现队列中计算的 TDI ，对高（24 个月截止值）和低（18 个月截止值）OS 进行了预测（准确性=87%）。
在这项研究中，GBM 累及白质束密度低的区域与更长的 OS 相关。这些发现表明，TDI 是一种可靠的术前预后预测指标，可在临床试验和临床实践中考虑。这些发现支持了一种框架，即 GBM 的结果取决于患者的大脑组织。
