Department of Clinical Sciences Lund, Division of Neurology, Lund University, Skane University Hospital, Lund, Sweden; Department of Clinical Sciences Lund, Division of Diagnostic Radiology, Lund University, Skane University Hospital, Lund, Sweden.
Department of Clinical Sciences Lund, Division of Neurosurgery, Lund University, Skane University Hospital, Lund, Sweden.
Magn Reson Imaging. 2023 Dec;104:88-96. doi: 10.1016/j.mri.2023.09.005. Epub 2023 Sep 19.
Early detection of treatment response is important for the management of patients with malignant brain tumors such as glioblastoma to assure good quality of life in relation to therapeutic efficacy.
To investigate whether parametric response mapping (PRM) with diffusion MRI may provide prognostic information at an early stage of standard therapy for glioblastoma.
This prospective study included 31 patients newly diagnosed with glioblastoma WHO grade IV, planned for primary standard postoperative treatment with radiotherapy 60Gy/30 fractions with concomitant and adjuvant Temozolomide. MRI follow-up including diffusion and perfusion weighting was performed at 3 T at start of postoperative chemoradiotherapy, three weeks into treatment, and then regularly until twelve months postoperatively. Regional mean diffusivity (MD) changes were analyzed voxel-wise using the PRM method (MD-PRM). At eight and twelve months postoperatively, after completion of standard treatment, patients were classified using conventional MRI and clinical evaluation as either having stable disease (SD, including partial response) or progressive disease (PD). It was assessed whether MD-PRM differed between patients having SD versus PD and whether it predicted the risk of disease progression (progression-free survival, PFS) or death (overall survival, OS). A subgroup analysis was performed that compared MD-PRM between SD and PD in patients only undergoing diagnostic biopsy. MGMT-promotor methylation status (O6-methylguanine-DNA methyltransferase) was registered and analyzed with respect to PFS, OS and MD-PRM.
Of the 31 patients analyzed: 21 were operated by resection and ten by diagnostic biopsy. At eight months, 19 patients had SD and twelve had PD. At twelve months, ten patients had SD and 20 had PD, out of which ten were deceased within twelve months and one was deceased without known tumor progression. Median PFS was nine months, and median OS was 17 months. Eleven patients had methylated MGMT-promotor, 16 were MGMT unmethylated, and four had unknown MGMT-status. MD-PRM did not significantly predict patients having SD versus PD neither at eight nor at twelve months. Patients with an above median MD-PRM reduction had a slightly longer PFS (P = 0.015) in Kaplan-Maier analysis, as well as a non-significantly longer OS (P = 0.099). In the subgroup of patients only undergoing biopsy, total MD-PRM change at three weeks was generally higher for patients with SD than for patients with PD at eight months, although no tests were performed. MGMT status strongly predicted both PFS and OS but not MD-PRM change.
MD-PRM at three weeks was not demonstrated to be predictive of treatment response, disease progression, or survival. Preliminary results suggested a higher predictive value in non-resected patients, although this needs to be evaluated in future studies.
对于胶质母细胞瘤等恶性脑肿瘤患者，早期检测治疗反应对于确保治疗效果相关的生活质量非常重要。
探讨扩散 MRI 的参数响应映射（PRM）是否可以在胶质母细胞瘤标准治疗的早期提供预后信息。
本前瞻性研究纳入了 31 例新诊断为 IV 级胶质母细胞瘤的患者，计划接受原发性术后标准治疗，包括 60Gy/30 次分割的放疗，同时联合替莫唑胺辅助治疗。在术后放化疗开始时、治疗 3 周时以及之后定期进行 MRI 随访，包括弥散和灌注加权成像。使用 PRM 方法（MD-PRM）对局部平均弥散率（MD）变化进行基于体素的分析。术后 8 个月和 12 个月，在完成标准治疗后，根据常规 MRI 和临床评估，将患者分为疾病稳定（SD，包括部分缓解）和进展性疾病（PD）。评估 MD-PRM 是否在 SD 与 PD 患者之间存在差异，以及它是否可以预测疾病进展（无进展生存期，PFS）或死亡（总生存期，OS）的风险。还进行了亚组分析，比较了仅行诊断性活检的 SD 和 PD 患者之间的 MD-PRM。MGMT 启动子甲基化状态（O6-甲基鸟嘌呤-DNA 甲基转移酶）被记录，并分析其与 PFS、OS 和 MD-PRM 的关系。
在分析的 31 例患者中：21 例行切除术，10 例行诊断性活检。8 个月时，19 例患者为 SD，12 例为 PD。12 个月时，10 例患者为 SD，20 例为 PD，其中 10 例在 12 个月内死亡，1 例死亡且无已知肿瘤进展。中位 PFS 为 9 个月，中位 OS 为 17 个月。11 例患者的 MGMT 启动子甲基化，16 例患者的 MGMT 未甲基化，4 例患者的 MGMT 状态未知。MD-PRM 既不能在 8 个月时也不能在 12 个月时预测 SD 与 PD 的患者。在 Kaplan-Meier 分析中，MD-PRM 降低超过中位数的患者 PFS 稍长（P=0.015），OS 也有非显著延长（P=0.099）。在仅行活检的亚组中，SD 患者在 3 周时的总 MD-PRM 变化通常高于 PD 患者，但在 8 个月时没有进行测试。MGMT 状态强烈预测 PFS 和 OS，但不预测 MD-PRM 变化。
在 3 周时的 MD-PRM 未显示出对治疗反应、疾病进展或生存的预测价值。初步结果表明，在非切除患者中有更高的预测价值，但需要在未来的研究中进行评估。
