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基于磁共振波谱成像的生物标志物在一项临床试验中预测新诊断胶质母细胞瘤的生存期

Spectroscopic MRI-Based Biomarkers Predict Survival for Newly Diagnosed Glioblastoma in a Clinical Trial.

作者信息

Trivedi Anuradha G, Ramesh Karthik K, Huang Vicki, Mellon Eric A, Barker Peter B, Kleinberg Lawrence R, Weinberg Brent D, Shu Hui-Kuo G, Shim Hyunsuk

机构信息

Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA.

出版信息

Cancers (Basel). 2023 Jul 7;15(13):3524. doi: 10.3390/cancers15133524.

Abstract

Despite aggressive treatment, glioblastoma has a poor prognosis due to its infiltrative nature. Spectroscopic MRI-measured brain metabolites, particularly the choline to N-acetylaspartate ratio (Cho/NAA), better characterizes the extent of tumor infiltration. In a previous pilot trial (NCT03137888), brain regions with Cho/NAA ≥ 2x normal were treated with high-dose radiation for newly diagnosed glioblastoma patients. This report is a secondary analysis of that trial where spectroscopic MRI-based biomarkers are evaluated for how they correlate with progression-free and overall survival (PFS/OS). Subgroups were created within the cohort based on pre-radiation treatment (pre-RT) median cutoff volumes of residual enhancement (2.1 cc) and metabolically abnormal volumes used for treatment (19.2 cc). We generated Kaplan-Meier PFS/OS curves and compared these curves via the log-rank test between subgroups. For the subgroups stratified by metabolic abnormality, statistically significant differences were observed for PFS ( = 0.019) and OS ( = 0.020). Stratification by residual enhancement did not lead to observable differences in the OS ( = 0.373) or PFS ( = 0.286) curves. This retrospective analysis shows that patients with lower post-surgical Cho/NAA volumes had significantly superior survival outcomes, while residual enhancement, which guides high-dose radiation in standard treatment, had little significance in PFS/OS. This suggests that the infiltrating, non-enhancing component of glioblastoma is an important factor in patient outcomes and should be treated accordingly.

摘要

尽管进行了积极治疗,但胶质母细胞瘤因其浸润性本质,预后较差。磁共振波谱成像(MRI)测量的脑代谢物,特别是胆碱与N-乙酰天门冬氨酸比值(Cho/NAA),能更好地表征肿瘤浸润程度。在之前的一项试点试验(NCT03137888)中,对于新诊断的胶质母细胞瘤患者,Cho/NAA≥2倍正常水平的脑区接受了高剂量放疗。本报告是对该试验的二次分析,评估基于MRI波谱的生物标志物与无进展生存期和总生存期(PFS/OS)的相关性。根据放疗前(pre-RT)残余强化的中位截断体积(2.1 cc)和用于治疗的代谢异常体积(19.2 cc)在队列中创建亚组。我们生成了Kaplan-Meier PFS/OS曲线,并通过对数秩检验比较亚组间的这些曲线。对于按代谢异常分层的亚组,PFS(=0.019)和OS(=0.020)观察到统计学显著差异。按残余强化分层未导致OS(=0.373)或PFS(=0.286)曲线出现可观察到的差异。这项回顾性分析表明,术后Cho/NAA体积较低的患者生存结果显著更优,而在标准治疗中指导高剂量放疗的残余强化在PFS/OS方面意义不大。这表明胶质母细胞瘤的浸润性、无强化成分是影响患者预后的重要因素,应相应地进行治疗。

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