磁共振波谱分析作为复发性胶质母细胞瘤患者抗血管生成治疗反应的早期指标：RTOG 0625/ACRIN 6677。
Magnetic resonance spectroscopy as an early indicator of response to anti-angiogenic therapy in patients with recurrent glioblastoma: RTOG 0625/ACRIN 6677.
机构信息
A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Department of Radiology, Neuroradiology Division, Harvard Medical School, Building 149, 13th Street, Room 2301, Charlestown, MA 02129, USA.
出版信息
Neuro Oncol. 2013 Jul;15(7):936-44. doi: 10.1093/neuonc/not044. Epub 2013 May 3.
BACKGROUND
The prognosis for patients with recurrent glioblastoma remains poor. The purpose of this study was to assess the potential role of MR spectroscopy as an early indicator of response to anti-angiogenic therapy.
METHODS
Thirteen patients with recurrent glioblastoma were enrolled in RTOG 0625/ACRIN 6677, a prospective multicenter trial in which bevacizumab was used in combination with either temozolomide or irinotecan. Patients were scanned prior to treatment and at specific timepoints during the treatment regimen. Postcontrast T1-weighted MRI was used to assess 6-month progression-free survival. Spectra from the enhancing tumor and peritumoral regions were defined on the postcontrast T1-weighted images. Changes in the concentration ratios of n-acetylaspartate/creatine (NAA/Cr), choline-containing compounds (Cho)/Cr, and NAA/Cho were quantified in comparison with pretreatment values.
RESULTS
NAA/Cho levels increased and Cho/Cr levels decreased within enhancing tumor at 2 weeks relative to pretreatment levels (P = .048 and P = .016, respectively), suggesting a possible antitumor effect of bevacizumab with cytotoxic chemotherapy. Nine of the 13 patients were alive and progression free at 6 months. Analysis of receiver operating characteristic curves for NAA/Cho changes in tumor at 8 weeks revealed higher levels in patients progression free at 6 months (area under the curve = 0.85), suggesting that NAA/Cho is associated with treatment response. Similar results were observed for receiver operating characteristic curve analyses against 1-year survival. In addition, decreased Cho/Cr and increased NAA/Cr and NAA/Cho in tumor periphery at 16 weeks posttreatment were associated with both 6-month progression-free survival and 1-year survival.
CONCLUSION
Changes in NAA and Cho by MR spectroscopy may potentially be useful as imaging biomarkers in assessing response to anti-angiogenic treatment.
背景
复发性胶质母细胞瘤患者的预后仍然较差。本研究旨在评估磁共振波谱分析作为抗血管生成治疗反应的早期指标的潜力。
方法
13 名复发性胶质母细胞瘤患者入组 RTOG 0625/ACRIN 6677 前瞻性多中心试验，该试验中贝伐单抗与替莫唑胺或伊立替康联合使用。患者在治疗前和治疗方案的特定时间点进行扫描。对比增强 T1 加权 MRI 用于评估 6 个月无进展生存期。在对比增强 T1 加权图像上定义增强肿瘤和肿瘤周围区域的光谱。与预处理值相比，定量比较 N-乙酰天冬氨酸/肌酐（NAA/Cr）、含胆碱化合物（Cho）/Cr 和 NAA/Cho 的浓度比变化。
结果
与预处理水平相比，在 2 周时增强肿瘤内的 NAA/Cho 水平升高，Cho/Cr 水平降低（P=0.048 和 P=0.016），提示贝伐单抗联合细胞毒性化疗可能具有抗肿瘤作用。13 名患者中有 9 名在 6 个月时存活且无进展。对肿瘤 8 周时 NAA/Cho 变化的受试者工作特征曲线分析显示，无进展生存期 6 个月的患者曲线下面积较高（曲线下面积=0.85），提示 NAA/Cho 与治疗反应相关。针对 1 年生存率的受试者工作特征曲线分析也得到了类似的结果。此外，治疗后 16 周肿瘤边缘的 Cho/Cr 降低和 NAA/Cr 和 NAA/Cho 升高与 6 个月无进展生存期和 1 年生存率均相关。
结论
磁共振波谱分析中 NAA 和 Cho 的变化可能作为评估抗血管生成治疗反应的成像生物标志物具有潜在的应用价值。
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