动态对比灌注 MRI 预测新诊断胶质母细胞瘤贝伐珠单抗早期应答的价值：ACRIN 6686 多中心试验结果。
Value of dynamic contrast perfusion MRI to predict early response to bevacizumab in newly diagnosed glioblastoma: results from ACRIN 6686 multicenter trial.
机构信息
Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin.
Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
出版信息
Neuro Oncol. 2021 Feb 25;23(2):314-323. doi: 10.1093/neuonc/noaa167.
BACKGROUND
In Radiation Therapy Oncology Group (RTOG) 0825, a phase III trial of standard therapy with bevacizumab or without (placebo) in newly diagnosed glioblastoma, 44 patients underwent dynamic contrast enhanced (DCE) and/or dynamic susceptibility contrast (DSC) MRI in the American College of Radiology Imaging Network (ACRIN) trial 6686. The association between early changes in relative cerebral blood volume (rCBV) and volume transfer constant (Ktrans) with overall survival (OS) was evaluated.
METHODS
MRI was performed at postop baseline (S0), immediately before (S1), 1 day after (S2), and 7 weeks after (S3) bevacizumab or placebo initiation. Mean normalized and standardized rCBV (nRCBV, sRCBV) and Ktrans were measured within contrast-enhancing lesion. Wilcoxon rank sum tests compared parameter changes from S1-S2 and S1-S3. Association with OS and progression-free survival (PFS) were determined using Kaplan-Meier and log-rank tests. Treatment response for groups stratified by pretreatment nRCBV (S0, S1) was explored. The intraclass correlation coefficient and repeatability coefficient for the placebo arm (S1-S2) were used to assess repeatability.
RESULTS
Evaluable were 27-36 datasets per time point. Significant differences between treatment arms were found for changes in nRCBV and sRCBV from S1-S2 and S1-S3, and in Ktrans for S1-S3. Improved PFS (P = 0.05) but not OS (P = 0.46) was observed. High pretreatment rCBV predicted improved OS for bevacizumab-treated patients. Based on the intraclass correlation coefficient, sRCBV (0.92) was more repeatable than nRCBV (0.71) and Ktrans (0.75), consistent with repeatability coefficient values.
CONCLUSIONS
Bevacizumab significantly changes rCBV but not Ktrans as early as 1 day posttreatment in newly diagnosed glioblastoma unrelated to outcomes. Improvements in clinical trial design to maximize rCBV benefit are indicated.
背景
在放射治疗肿瘤学组（RTOG）0825 中，一项关于贝伐单抗标准治疗的 III 期试验，在新诊断的胶质母细胞瘤中使用贝伐单抗或不使用（安慰剂），44 名患者在美国放射学院影像学网络（ACRIN）试验 6686 中进行了动态对比增强（DCE）和/或动态磁敏感对比（DSC）MRI。评估了相对脑血容量（rCBV）和容积转移常数（Ktrans）的早期变化与总生存期（OS）的相关性。
方法
MRI 在贝伐单抗或安慰剂开始前的术后基线（S0）、立即（S1）、1 天（S2）和 7 周（S3）进行。在对比增强病变内测量平均归一化和标准化 rCBV（nRCBV，sRCBV）和 Ktrans。Wilcoxon 秩和检验比较了 S1-S2 和 S1-S3 期间参数的变化。使用 Kaplan-Meier 和对数秩检验确定与 OS 和无进展生存期（PFS）的相关性。使用治疗前 nRCBV（S0，S1）分层的组的治疗反应进行探索。安慰剂组（S1-S2）的组内相关系数和重复性系数用于评估重复性。
结果
每个时间点可评估的数据集为 27-36 个。在 S1-S2 和 S1-S3 时，nRCBV 和 sRCBV 的变化以及 S1-S3 时的 Ktrans 治疗臂之间存在显著差异。观察到 PFS（P = 0.05）但不是 OS（P = 0.46）的改善。高治疗前 rCBV 预测贝伐单抗治疗患者的 OS 改善。根据组内相关系数，sRCBV（0.92）比 nRCBV（0.71）和 Ktrans（0.75）更具重复性，与重复性系数值一致。
结论
贝伐单抗在新诊断的胶质母细胞瘤中，在治疗后 1 天内即可显著改变 rCBV，但与结果无关。需要改进临床试验设计以最大限度地提高 rCBV 的获益。
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