Departments of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
J Neurosurg. 2012 Apr;116(4):835-42. doi: 10.3171/2011.12.JNS111255. Epub 2012 Jan 13.
Immunotherapy targeting the Wilms tumor 1 (WT1) gene product is a promising treatment modality for patients with malignant gliomas, and there have been reports of encouraging results. It has become clear, however, that Gd-enhanced MR imaging does not reflect prognosis, thereby necessitating a more robust imaging evaluation system for monitoring response to WT1 immunotherapy. To meet this demand, the authors performed a voxel-wise parametric response map (PRM) analysis of (11)C-methionine PET (MET-PET) in WT1 immunotherapy and compared the data with the overall survival after initiation of WT1 immunotherapy (OS(WT1)).
Fourteen patients with recurrent malignant glioma were included in the study, and OS(WT1) was compared with: 1) volume and length change in the contrast area of the tumor on Gd-enhanced MR images; 2) change in maximum uptake of (11)C-methionine; and 3) a more detailed voxel-wise PRM analysis of MET-PET pre- and post-WT1 immunotherapy.
The PRM analysis was able to identify the following 3 areas within the tumor core: 1) area with no change in (11)C-methionine uptake pre- and posttreatment; 2) area with increased (11)C-methionine uptake posttreatment (PRM(+MET)); and 3) area with decreased (11)C-methionine uptake posttreatment. While the results of Gd-enhanced MR imaging volumetric and conventional MET-PET analysis did not correlate with OS(WT1) (p = 0.270 for Gd-enhanced MR imaging length, p = 0.960 for Gd-enhanced MR imaging volume, and p = 0.110 for MET-PET), the percentage of PRM(+MET) area showed excellent correlation (p = 0.008) with OS(WT1).
This study describes the limited value of Gd-enhanced MR imaging and highlights the potential of voxel-wise PRM analysis of MET-PET for monitoring treatment response in immunotherapy for malignant gliomas. Clinical trial registration no.: UMIN000002001.
针对 Wilms 肿瘤 1（WT1）基因产物的免疫疗法是治疗恶性神经胶质瘤患者的一种有前途的治疗方法，已有令人鼓舞的结果报告。然而，已经清楚的是，钆增强磁共振成像并不能反映预后，因此需要更强大的成像评估系统来监测 WT1 免疫疗法的反应。为了满足这一需求，作者对 WT1 免疫治疗中的（11）C-蛋氨酸 PET（MET-PET）进行了体素参数响应图（PRM）分析，并将数据与 WT1 免疫治疗开始后的总生存期（OS（WT1））进行了比较。
本研究纳入了 14 例复发性恶性神经胶质瘤患者，并将 OS（WT1）与以下指标进行了比较：1）肿瘤 Gd 增强磁共振图像对比区的体积和长度变化；2）（11）C-蛋氨酸最大摄取量的变化；3）WT1 免疫治疗前后 MET-PET 的更详细体素 PRM 分析。
PRM 分析能够识别肿瘤核心内的以下 3 个区域：1）治疗前后（11）C-蛋氨酸摄取无变化的区域；2）治疗后（11）C-蛋氨酸摄取增加的区域（PRM（+MET））；3）治疗后（11）C-蛋氨酸摄取减少的区域。虽然 Gd 增强磁共振成像体积和常规 MET-PET 分析的结果与 OS（WT1）无关（Gd 增强磁共振成像长度的 p = 0.270，Gd 增强磁共振成像体积的 p = 0.960，MET-PET 的 p = 0.110），但 PRM（+MET）区域的百分比与 OS（WT1）具有极好的相关性（p = 0.008）。
本研究描述了 Gd 增强磁共振成像的局限性，并强调了 MET-PET 体素 PRM 分析在监测恶性神经胶质瘤免疫治疗反应中的潜力。临床试验注册号：UMIN000002001。
