Abstract

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 (K^trans) 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 K^trans 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 K^trans 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 K^trans (0.75), consistent with repeatability coefficient values.

Conclusions

Bevacizumab significantly changes rCBV but not K^trans as early as 1 day posttreatment in newly diagnosed glioblastoma unrelated to outcomes. Improvements in clinical trial design to maximize rCBV benefit are indicated.

中文翻译：

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动态对比灌注 MRI 预测新诊断胶质母细胞瘤对贝伐珠单抗早期反应的价值：ACRIN 6686 多中心试验的结果

摘要

背景

在肿瘤放射治疗组 (RTOG) 0825 中，一项使用贝伐珠单抗或不使用（安慰剂）标准疗法治疗新诊断胶质母细胞瘤的 III 期试验中，44 名患者接受了动态对比增强 (DCE) 和/或动态磁敏感对比 (DSC) MRI美国放射成像网络学院 (ACRIN) 试验 6686。评估了相对脑血容量 (rCBV) 和体积转移常数 (K ^trans )的早期变化与总生存期 (OS) 之间的关联。

方法

MRI 在术后基线 (S0)、贝伐单抗或安慰剂开始前 (S1)、术后 1 天 (S2) 和术后 7 周 (S3) 时进行。在对比增强病变内测量平均归一化和标准化 rCBV（nRCBV、sRCBV）和 K^反式。Wilcoxon 秩和检验比较了 S1–S2 和 S1–S3 的参数变化。使用 Kaplan–Meier 和对数秩检验确定与 OS 和无进展生存期 (PFS) 的关联。探索了按治疗前 nRCBV (S0, S1) 分层的组的治疗反应。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 27-36 个数据集。对于 S1-S2 和 S1-S3 的 nRCBV 和 sRCBV 变化以及S1-S3 的K^反式变化，治疗组之间存在显着差异。观察到改善的 PFS ( P = 0.05) 但没有改善 OS ( P = 0.46)。高预处理 rCBV 预测贝伐珠单抗治疗患者的 OS 改善。基于组内相关系数，sRCBV (0.92) 比 nRCBV (0.71) 和 K ^trans (0.75) 更具可重复性，与可重复性系数值一致。

结论

早在治疗后 1 天，贝伐珠单抗就显着改变了 rCBV 但不改变 K^{反式，与结果无关。}指出了临床试验设计的改进，以最大限度地提高 rCBV 的益处。