在复发性胶质母细胞瘤中，使用贝伐单抗联合或不联合VB-111的随机III期试验验证扩散磁共振成像作为疗效生物标志物的作用。
Validation of diffusion MRI as a biomarker for efficacy using randomized phase III trial of bevacizumab with or without VB-111 in recurrent glioblastoma.
作者信息
Ellingson Benjamin M, Patel Kunal, Wang Chencai, Raymond Catalina, Brenner Andrew, de Groot John F, Butowski Nicholas A, Zach Leor, Campian Jian L, Schlossman Jacob, Rizvi Shan, Cohen Yael C, Lowenton-Spier Noa, Minei Tamar Rachmilewitz, Shmueli Shifra Fain, Wen Patrick Y, Cloughesy Timothy F
机构信息
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, USA.
Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
出版信息
Neurooncol Adv. 2021 Jun 19;3(1):vdab082. doi: 10.1093/noajnl/vdab082. eCollection 2021 Jan-Dec.
BACKGROUND
Evidence from single and multicenter phase II trials have suggested diffusion MRI is a predictive imaging biomarker for survival benefit in recurrent glioblastoma (rGBM) treated with anti-VEGF therapy. The current study confirms these findings in a large, randomized phase III clinical trial.
METHODS
Patients with rGBM were enrolled in a phase III randomized (1:1), controlled trial (NCT02511405) to compare the efficacy and safety of bevacizumab (BV) versus BV in combination with ofranergene obadenovec (BV+VB-111), an anti-cancer viral therapy. In 170 patients with diffusion MRI available, pretreatment enhancing tumor volume and ADC histogram analysis were used to phenotype patients as having high (>1.24 µm/ms) or low (<1.24 µm/ms) ADC, the mean value of the lower peak of the ADC histogram, within the contrast enhancing tumor.
RESULTS
Baseline tumor volume ( = .3460) and ADC ( = .2143) did not differ between treatment arms. Univariate analysis showed patients with high ADC had a significant survival advantage in all patients ( = .0006), as well as BV ( = .0159) and BV+VB-111 individually ( = .0262). Multivariable Cox regression accounting for treatment arm, age, baseline tumor volume, and ADC identified continuous measures of tumor volume ( < .0001; HR = 1.0212) and ADC phenotypes ( = .0012; HR = 0.5574) as independent predictors of OS.
CONCLUSION
Baseline diffusion MRI and tumor volume are independent imaging biomarkers of OS in rGBM treated with BV or BV+VB-111.
背景
单中心和多中心II期试验的证据表明，弥散磁共振成像（diffusion MRI）是接受抗血管内皮生长因子（VEGF）治疗的复发性胶质母细胞瘤（rGBM）生存获益的预测性影像生物标志物。本研究在一项大型随机III期临床试验中证实了这些发现。
方法
rGBM患者被纳入一项III期随机（1:1）对照试验（NCT02511405），以比较贝伐单抗（BV）与BV联合抗癌病毒疗法奥弗兰基因奥巴德诺韦克（BV+VB-111）的疗效和安全性。在170例有弥散MRI数据的患者中，利用治疗前强化肿瘤体积和表观扩散系数（ADC）直方图分析，将患者表型为对比增强肿瘤内ADC高（>1.24 µm/ms）或低（<1.24 µm/ms），ADC直方图较低峰的平均值。
结果
各治疗组间基线肿瘤体积（P = 0.3460）和ADC（P = 0.2143）无差异。单因素分析显示，高ADC患者在所有患者中具有显著的生存优势（P = 0.0006），在接受BV治疗的患者中（P = 0.0159）以及接受BV+VB-111治疗的患者中均有显著生存优势（P = 0.0262）。多变量Cox回归分析纳入治疗组、年龄、基线肿瘤体积和ADC，结果表明肿瘤体积的连续测量值（P < 0.0001；风险比[HR] = 1.0212）和ADC表型（P = 0.0012；HR = 0.5574）是总生存期（OS）的独立预测因素。
结论
基线弥散MRI和肿瘤体积是接受BV或BV+VB-111治疗的rGBM患者OS的独立影像生物标志物。
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