UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
Clin Cancer Res. 2017 Oct 1;23(19):5745-5756. doi: 10.1158/1078-0432.CCR-16-2844. Epub 2017 Jun 27.
Anti-VEGF therapies remain controversial in the treatment of recurrent glioblastoma (GBM). In the current study, we demonstrate that recurrent GBM patients with a specific diffusion MR imaging signature have an overall survival (OS) advantage when treated with cediranib, bevacizumab, cabozantinib, or aflibercept monotherapy at first or second recurrence. These findings were validated using a separate trial comparing bevacizumab with lomustine. Patients with recurrent GBM and diffusion MRI from the monotherapy arms of 5 separate phase II clinical trials were included: (i) cediranib (NCT00035656); (ii) bevacizumab (BRAIN Trial, AVF3708g; NCT00345163); (iii) cabozantinib (XL184-201; NCT00704288); (iv) aflibercept (VEGF Trap; NCT00369590); and (v) bevacizumab or lomustine (BELOB; NTR1929). Apparent diffusion coefficient (ADC) histogram analysis was performed prior to therapy to estimate "ADC," the mean of the lower ADC distribution. Pretreatment ADC, enhancing volume, and clinical variables were tested as independent prognostic factors for OS. The coefficient of variance (COV) in double baseline ADC measurements was 2.5% and did not significantly differ ( = 0.4537). An ADC threshold of 1.24 μm/ms produced the largest OS differences between patients (HR ∼ 0.5), and patients with an ADC > 1.24 μm/ms had close to double the OS in all anti-VEGF therapeutic scenarios tested. Training and validation data confirmed that baseline ADC was an independent predictive biomarker for OS in anti-VEGF therapies, but not in lomustine, after accounting for age and baseline enhancing tumor volume. Pretreatment diffusion MRI is a predictive imaging biomarker for OS in patients with recurrent GBM treated with anti-VEGF monotherapy at first or second relapse. .
抗血管内皮生长因子治疗在复发性胶质母细胞瘤（GBM）的治疗中仍存在争议。在目前的研究中，我们证明在首次或第二次复发时，接受西地尼布、贝伐珠单抗、卡博替尼或阿柏西普单药治疗的具有特定弥散磁共振成像特征的复发性 GBM 患者具有总生存（OS）优势。这些发现通过比较贝伐珠单抗与洛莫司汀的单独试验得到了验证。来自 5 项单独的 II 期临床试验的单药治疗臂的复发性 GBM 患者和弥散 MRI 患者被纳入：（i）西地尼布（NCT00035656）；（ii）贝伐珠单抗（BRAIN 试验，AVF3708g；NCT00345163）；（iii）卡博替尼（XL184-201；NCT00704288）；（iv）阿柏西普（VEGF Trap；NCT00369590）；和（v）贝伐珠单抗或洛莫司汀（BELOB；NTR1929）。在治疗前进行表观扩散系数（ADC）直方图分析，以估计“ADC”，即较低 ADC 分布的平均值。在治疗前的 ADC、增强体积和临床变量被测试为 OS 的独立预后因素。两次基线 ADC 测量的变异系数（COV）为 2.5%，且差异无统计学意义（=0.4537）。ADC 阈值为 1.24μm/ms 时，在所有接受抗 VEGF 治疗的患者中，OS 差异最大（HR≈0.5），且 ADC>1.24μm/ms 的患者在所有接受抗 VEGF 治疗的患者中，OS 接近两倍。训练和验证数据证实，在考虑年龄和基线增强肿瘤体积后，基线 ADC 是抗 VEGF 治疗中 OS 的独立预测生物标志物，但在洛莫司汀中不是。治疗前弥散 MRI 是接受抗 VEGF 单药治疗的复发性 GBM 患者的预测 OS 的影像学生物标志物，而在首次或第二次复发时则不是。
