From the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Neuroradiology Division (M.E.E., M.R.W., M.F., D.K., A.W., J.H., A.V., M.V., O.R., O.A., Y.F.Y., B.R., R.G.G., E.M.R.), and Department of Neurosurgery (P.T.), Massachusetts General Hospital, Harvard Medical School, Building 149, 13th St, Room 2301, Charlestown, MA 02129; and Massachusetts General Hospital Cancer Center, Boston, Mass (I.A.R., D.A.F., T.T.B., J.D., E.R.G.).
Radiology. 2022 Feb;302(2):410-418. doi: 10.1148/radiol.2021210826. Epub 2021 Nov 9.
Background Patients with recurrent glioblastoma (GBM) are often treated with antiangiogenic agents, such as bevacizumab (BEV). Despite therapeutic promise, conventional MRI methods fail to help determine which patients may not benefit from this treatment. Purpose To use MR spectroscopic imaging (MRSI) with intermediate and short echo time to measure corrected myo-inositol (mI)normalized by contralateral creatine (hereafter, mI/c-Cr) in participants with recurrent GBM treated with BEV and to investigate whether such measurements can help predict survivorship before BEV initiation (baseline) and at 1 day, 4 weeks, and 8 weeks thereafter. Materials and Methods In this prospective longitudinal study (2016-2020), spectroscopic data on mI-a glial marker and osmoregulator within the brain-normalized by contralateral creatine in the intratumoral, contralateral, and peritumoral volumes of patients with recurrent GBM were evaluated. Area under the receiver operating characteristic curve (AUC) was calculated for all volumes at baseline and 1 day, 4 weeks, and 8 weeks after treatment to determine the ability of mI/c-Cr to help predict survivorship. Results Twenty-one participants (median age ± standard deviation, 62 years ± 12; 15 men) were evaluated. Lower mI/c-Cr in the tumor before and during BEV treatment was predictive of poor survivorship, with receiver operating characteristic analyses showing an AUC of 0.75 at baseline, 0.87 at 1 day after treatment, and 1 at 8 weeks after. A similar result was observed in contralateral normal-appearing tissue and the peritumoral volume, with shorter-term survivors having lower levels of mI/c-Cr. In the contralateral volume, a lower ratio of mI to creatine (hereafter, mI/Cr) predicted shorter-term survival at baseline and all other time points. Within the peritumoral volume, lower mI/c-Cr levels were predictive of shorter-term survival at baseline (AUC, 0.80), at 1 day after treatment (AUC, 0.93), and at 4 weeks after treatment (AUC, 0.68). Conclusion Lower levels of myo-inositol normalized by contralateral creatine within intratumoral, contralateral, and peritumoral volumes were predictive of poor survivorship and antiangiogenic treatment failure as early as before bevacizumab treatment. Adapting MR spectroscopic imaging alongside conventional MRI modalities conveys critical information regarding the biologic characteristics of tumors to help better treat individuals with recurrent glioblastoma. Clinical trial registration no. NCT02843230 © RSNA, 2021 .
背景 复发性胶质母细胞瘤(GBM)患者常接受抗血管生成药物治疗,如贝伐珠单抗(bevacizumab,BEV)。尽管有治疗前景,但常规 MRI 方法无法帮助确定哪些患者可能无法从这种治疗中获益。目的 使用中间和短回波时间的磁共振波谱成像(MRSI)测量接受 BEV 治疗的复发性 GBM 患者的校正肌醇(mI)与对侧肌酸(creatine,Cr)的比值(此后称为 mI/c-Cr),并探讨这些测量值是否可以帮助预测 BEV 起始前(基线)和治疗后 1 天、4 周和 8 周的生存情况。材料与方法 本前瞻性纵向研究(2016-2020 年)评估了复发性 GBM 患者肿瘤内、对侧和肿瘤周围容积内 mI-a 脑内神经胶质标志物和渗透压调节剂与对侧 Cr 比值的 MRSI 数据。计算所有容积在基线和治疗后 1 天、4 周和 8 周时的受试者工作特征曲线下面积(AUC),以确定 mI/c-Cr 预测生存情况的能力。结果 21 名参与者(中位年龄±标准差,62 岁±12 岁;15 名男性)接受了评估。在 BEV 治疗前和治疗期间肿瘤内 mI/c-Cr 降低与预后不良相关,受试者工作特征分析显示基线时 AUC 为 0.75,治疗后 1 天为 0.87,治疗后 8 周为 1。在对侧正常组织和肿瘤周围容积中也观察到类似的结果,短期存活者的 mI/c-Cr 水平较低。在对侧容积中,mI 与 Cr 的比值(mI/Cr)降低可预测基线和所有其他时间点的短期生存。在肿瘤周围容积中,基线时 mI/c-Cr 水平降低(AUC,0.80)、治疗后 1 天(AUC,0.93)和治疗后 4 周(AUC,0.68)预测短期生存。结论 在肿瘤内、对侧和肿瘤周围容积内,由对侧 Cr 标准化的肌醇水平降低可预测预后不良和抗血管生成治疗失败,甚至早在 BEV 治疗之前。结合常规 MRI 模式改编磁共振波谱成像可提供有关肿瘤生物学特征的关键信息,有助于更好地治疗复发性胶质母细胞瘤患者。临床试验注册号 NCT02843230©RSNA,2021 。