UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, 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. 2023 Oct 13;29(20):4186-4195. doi: 10.1158/1078-0432.CCR-23-1235.
Antiangiogenic therapies are known to cause high radiographic response rates due to reduction in vascular permeability resulting in a lower degree of contrast extravasation. In this study, we investigate the prognostic ability for model-derived parameters describing enhancing tumor volumetric dynamics to predict survival in recurrent glioblastoma treated with antiangiogenic therapy.
N = 276 patients in two phase II trials were used as training data, including bevacizumab ± irinotecan (NCT00345163) and cabozantinib (NCT00704288), and N = 74 patients in the bevacizumab arm of a phase III trial (NCT02511405) were used for validation. Enhancing volumes were estimated using T1 subtraction maps, and a biexponential model was used to estimate regrowth (g) and regression (d) rates, time to tumor regrowth (TTG), and the depth of response (DpR). Response characteristics were compared to diffusion MR phenotypes previously shown to predict survival.
Optimized thresholds occurred at g = 0.07 months-1 (phase II: HR = 0.2579, P = 5 × 10-20; phase III: HR = 0.2197, P = 5 × 10-5); d = 0.11 months-1 (HR = 0.3365, P < 0.0001; HR = 0.3675, P = 0.0113); TTG = 3.8 months (HR = 0.2702, P = 6 × 10-17; HR = 0.2061, P = 2 × 10-5); and DpR = 11.3% (HR = 0.6326, P = 0.0028; HR = 0.4785, P = 0.0206). Multivariable Cox regression controlling for age and baseline tumor volume confirmed these factors as significant predictors of survival. Patients with a favorable pretreatment diffusion MRI phenotype had a significantly longer TTG and slower regrowth.
Recurrent glioblastoma patients with a large, durable radiographic response to antiangiogenic agents have significantly longer survival. This information is useful for interpreting activity of antiangiogenic agents in recurrent glioblastoma.
血管生成抑制剂可降低血管通透性，导致对比外渗程度降低，从而导致高放射学反应率。在这项研究中，我们研究了描述增强肿瘤容积动力学的模型衍生参数对接受抗血管生成治疗的复发性胶质母细胞瘤患者生存的预测能力。
我们将两项 II 期临床试验中的 276 例患者（N = 276）作为训练数据，包括贝伐单抗+伊立替康（NCT00345163）和卡博替尼（NCT00704288），并将三项 III 期试验中贝伐单抗组的 74 例患者（NCT02511405）作为验证数据。使用 T1 减影图估算增强体积，并使用双指数模型估算再生长（g）和消退（d）率、肿瘤再生长时间（TTG）和反应深度（DpR）。将反应特征与先前显示可预测生存的扩散磁共振表型进行比较。
在 g = 0.07 个月-1 时出现最佳阈值（II 期：HR = 0.2579，P = 5×10-20；III 期：HR = 0.2197，P = 5×10-5）；d = 0.11 个月-1（HR = 0.3365，P < 0.0001；HR = 0.3675，P = 0.0113）；TTG = 3.8 个月（HR = 0.2702，P = 6×10-17；HR = 0.2061，P = 2×10-5）；DpR = 11.3%（HR = 0.6326，P = 0.0028；HR = 0.4785，P = 0.0206）。控制年龄和基线肿瘤体积的多变量 Cox 回归证实这些因素是生存的显著预测因素。具有良好预处理扩散 MRI 表型的复发性胶质母细胞瘤患者的 TTG 明显更长，再生长速度更慢。
接受抗血管生成药物治疗的复发性胶质母细胞瘤患者对放射性反应较大且持久，其生存时间明显延长。该信息有助于解释抗血管生成药物在复发性胶质母细胞瘤中的活性。
