Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.
Section for Computational Neuroimaging, Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.
Neuro Oncol. 2020 Nov 26;22(11):1667-1676. doi: 10.1093/neuonc/noaa120.
This study validated a previously described diffusion MRI phenotype as a potential predictive imaging biomarker in patients with recurrent glioblastoma receiving bevacizumab (BEV).
A total of 396/596 patients (66%) from the prospective randomized phase II/III EORTC-26101 trial (with n = 242 in the BEV and n = 154 in the non-BEV arm) met the inclusion criteria with availability of anatomical and diffusion MRI sequences at baseline prior treatment. Apparent diffusion coefficient (ADC) histograms from the contrast-enhancing tumor volume were fitted to a double Gaussian distribution and the mean of the lower curve (ADClow) was used for further analysis. The predictive ability of ADClow was assessed with biomarker threshold models and multivariable Cox regression for overall survival (OS) and progression-free survival (PFS).
ADClow was associated with PFS (hazard ratio [HR] = 0.625, P = 0.007) and OS (HR = 0.656, P = 0.031). However, no (predictive) interaction between ADClow and the treatment arm was present (P = 0.865 for PFS, P = 0.722 for OS). Independent (prognostic) significance of ADClow was retained after adjusting for epidemiological, clinical, and molecular characteristics (P ≤ 0.02 for OS, P ≤ 0.01 PFS). The biomarker threshold model revealed an optimal ADClow cutoff of 1241*10-6 mm2/s for OS. Thereby, median OS for BEV-patients with ADClow ≥ 1241 was 10.39 months versus 8.09 months for those with ADClow < 1241 (P = 0.004). Similarly, median OS for non-BEV patients with ADClow ≥ 1241 was 9.80 months versus 7.79 months for those with ADClow < 1241 (P = 0.054).
ADClow is an independent prognostic parameter for stratifying OS and PFS in patients with recurrent glioblastoma. Consequently, the previously suggested role of ADClow as predictive imaging biomarker could not be confirmed within this phase II/III trial.
本研究验证了一种先前描述的扩散 MRI 表型，作为接受贝伐珠单抗（BEV）治疗的复发性胶质母细胞瘤患者潜在的预测性影像学生物标志物。
共有 396/596 名（66%）来自前瞻性随机 II/III 期 EORTC-26101 试验的患者（BEV 组 242 名，非 BEV 组 154 名）符合纳入标准，治疗前基线时均有解剖和扩散 MRI 序列。对增强肿瘤体积的表观扩散系数（ADC）直方图进行双高斯拟合，使用下曲线的平均值（ADClow）进行进一步分析。采用生物标志物阈值模型和多变量 Cox 回归评估 ADClow 对总生存期（OS）和无进展生存期（PFS）的预测能力。
ADClow 与 PFS（风险比 [HR] = 0.625，P = 0.007）和 OS（HR = 0.656，P = 0.031）相关。然而，ADClow 与治疗组之间没有（预测）相互作用（PFS 的 P = 0.865，OS 的 P = 0.722）。调整流行病学、临床和分子特征后，ADClow 仍具有独立的（预后）意义（OS 的 P ≤ 0.02，PFS 的 P ≤ 0.01）。生物标志物阈值模型显示，OS 的最佳 ADClow 截断值为 1241*10-6mm2/s。因此，ADClow≥1241 的 BEV 患者的中位 OS 为 10.39 个月，而 ADClow<1241 的患者为 8.09 个月（P = 0.004）。同样，ADClow≥1241 的非 BEV 患者的中位 OS 为 9.80 个月，而 ADClow<1241 的患者为 7.79 个月（P = 0.054）。
ADClow 是复发性胶质母细胞瘤患者 OS 和 PFS 分层的独立预后参数。因此，在这项 II/III 期试验中，无法证实先前提出的 ADClow 作为预测性影像学生物标志物的作用。
