因血管通透性降低导致对比剂外渗程度降低，抗血管生成疗法已被证明可引起高的成像回应率。在本研究中，我们调查了描述增强肿瘤体积动力学的模型衍生参数对预测抗血管生成疗法治疗的复发性胶质母细胞瘤患者的存活的预测能力。 本研究选取了两项II期临床试验中的总共276例患者作为训练数据，其中包括贝伐单抗+/-依立替康 (NCT00345163) 和卡博替尼 (NCT00704288)，以及一项III期临床试验中贝伐单抗组的74例患者作为验证数据(NCT02511405)。通过使用T1减法图来估计增强体积，并采用双指数模型来估计复增长速率(g)和回归速率(d)，肿瘤再生时间(TTG)以及反应深度(DpR)。将响应特征与先前显示可预测生存的扩散MR表型进行比较。 优化后的阈值为 g=0.07月-1 (Phase II: HR=0.2579，P=5x10-20; Phase III: HR=0.2197，P=5x10-5)，d=0.11月-1 (HR=0.3365，P<0.0001; HR=0.3675，P=0.0113)，TTG=3.8月(HR=0.2702，P=6x10-17; HR=0.2061，P=2x10-5)，以及DpR=11.3% (HR=0.6326，P=0.0028; HR=0.4785，P=0.0206)。通过多变量Cox回归控制年龄和基线肿瘤体积，证实了这些因素作为生存预测的重要因子。具有有利的治疗前扩散性MRI表型的患者具有更长的TTG和较慢的再生速度。 对抗血管生成剂有大面积和持久成像反应的复发性胶质母细胞瘤患者具有显著较长的生存期。这些信息对解读抗血管生成剂在复发性胶质母细胞瘤中的作用具有重要意义。

Anti-angiogenic therapies are known to cause high radiographic response rates due to reduction in vascular permeability resulting in a lower degree of contrast extravasation. In the current study, we investigate the prognostic ability for model-derived parameters describing enhancing tumor volumetric dynamics to predict survival in recurrent glioblastoma treated with anti-angiogenic 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=0.07months-1 (phase II:HR=0.2579,P=5x10-20; phase III:HR=0.2197, P=5x10-5); d=0.11months-1 (HR=0.3365, P<0.0001; HR=0.3675,P=0.0113); TTG=3.8 months (HR=0.2702,P=6x10-17;HR=0.2061,P=2x10-5); 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 pre-treatment diffusion MRI phenotype had a significantly longer TTG and slower regrowth.Recurrent glioblastoma patients with a large, durable radiographic response to anti-angiogenic agents have significantly longer survival. This information is useful for interpreting activity of anti-angiogenic agents in recurrent glioblastoma.