From the Department of Radiology and Research Institute of Radiology (C.K., H.S.K., W.H.S., C.G.C., S.J.K.) and Department of Neurosurgery (J.H.K.), University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Seoul 138-736, Korea.
Radiology. 2017 Jan;282(1):212-221. doi: 10.1148/radiol.2016152152. Epub 2016 Jul 18.
Purpose To determine if the combination of high cerebral blood flow (CBF) and O-methylguanine DNA methyltransferase (MGMT) promoter methylation is associated with benefit from a second round of low-dose temozolomide (TMZ) (ie, rechallenge) in patients with glioblastoma at first recurrence. Materials and Methods The institutional review board approved this retrospective cohort study and waived the requirement for informed consent. Seventy-two patients with recurrent glioblastoma after concurrent TMZ radiation therapy were treated with a low-dose TMZ rechallenge and underwent arterial spin labeling magnetic resonance imaging. The cohort was dichotomized to high-CBF and low-CBF subgroups. MGMT promoter methylation was determined before concurrent TMZ radiation therapy. The coprimary end points were median time to progression (TTP) and 6-month outcome after the initiation of low-dose TMZ. The Cox proportional hazards model was used to assess the association between clinical outcome and CBF status. Results There was a significant difference between the high- and low-CBF cohorts in median TTP (6 months vs 3 months, respectively; P = .001). Favorable 6-month outcomes occurred in 16 of 31 (52%) patients with high CBF and six of 41 (15%) patients with low CBF (P = .001). At multivariate analysis, high CBF was independently associated with longer TTP (P = .023). The association between high CBF and favorable outcome was significant only in the MGMT promoter methylation group (P = .006 for TTP; P = .005 for 6-month outcome). Conclusion The combination of high CBF with MGMT methylation may be associated with benefits from a low-dose TMZ rechallenge in patients with recurrent glioblastoma. However, alternative strategies might be needed for patients with both low CBF and a lack of MGMT methylation. RSNA, 2016 Online supplemental material is available for this article.
确定在首次复发的胶质母细胞瘤患者中，高脑血流（CBF）与 O-甲基鸟嘌呤 DNA 甲基转移酶（MGMT）启动子甲基化的联合是否与接受第二轮低剂量替莫唑胺（TMZ）（即再挑战）获益相关。
机构审查委员会批准了这项回顾性队列研究，并豁免了知情同意的要求。72 例接受同步 TMZ 放疗后复发的胶质母细胞瘤患者接受低剂量 TMZ 再挑战治疗，并接受动脉自旋标记磁共振成像检查。该队列分为高 CBF 和低 CBF 亚组。在同步 TMZ 放疗前确定 MGMT 启动子甲基化状态。主要终点是低剂量 TMZ 起始后中位无进展生存期（TTP）和 6 个月结局。Cox 比例风险模型用于评估临床结局与 CBF 状态之间的关系。
高 CBF 组和低 CBF 组的中位 TTP 存在显著差异（分别为 6 个月和 3 个月；P =.001）。高 CBF 亚组中有 16 例（52%）患者和低 CBF 亚组中有 6 例（15%）患者的 6 个月结局良好（P =.001）。多变量分析显示，高 CBF 与 TTP 延长独立相关（P =.023）。仅在 MGMT 启动子甲基化组中，高 CBF 与良好结局之间存在显著关联（TTP：P =.006；6 个月结局：P =.005）。
在接受复发胶质母细胞瘤治疗的患者中，高 CBF 与 MGMT 甲基化的联合可能与低剂量 TMZ 再挑战获益相关。然而，对于 CBF 低且缺乏 MGMT 甲基化的患者，可能需要其他治疗策略。
放射学学会，2016 年
在线补充材料可从本文获取。
