Incorporation of Edited MRS into Clinical Practice May Improve Care of Patients with IDH-Mutant Glioma.

Lucia Nichelli, Capucine Cadin, Patrizia Lazzari, Bertrand Mathon, Mehdi Touat, Marc Sanson, Franck Bielle, Małgorzata Marjańska, Stéphane Lehéricy, Francesca Branzoli
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Abstract

Background and purpose: Isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion classify adult-type diffuse gliomas into 3 tumor subtypes with distinct prognoses. We aimed to evaluate the performance of edited MR spectroscopy for glioma subtyping in a clinical setting, via the quantification of D-2-hydroxyglutarate (2HG) and cystathionine. The delay between this noninvasive classification and the integrated histomolecular analysis was also quantified.

Materials and methods: Subjects with presumed low-grade gliomas eligible for surgery (cohort 1) and subjects with IDH-mutant gliomas previously treated and with progressive disease (cohort 2) were prospectively examined with a single-voxel Mescher-Garwood point-resolved spectroscopy sequence at 3T. Spectra were quantified using LCModel. The Cramér-Rao lower bounds threshold was set to 20%. Integrated histomolecular analysis according to the 2021 WHO classification was considered as ground truth.

Results: Thirty-four consecutive subjects were enrolled. Due to poor spectra quality and lack of histologic specimens, data from 26 subjects were analyzed. Twenty-one belonged to cohort 1 (11 women; median age, 42 years); and 5, to cohort 2 (3 women; median age, 48 years). Edited MR spectroscopy showed 100% specificity for detection of IDH-mutation and 91% specificity for the prediction of 1p/19q-codeletion status. Sensitivities for the prediction of IDH and 1p/19q codeletion were 69% and 33%, respectively. The median Cramér-Rao lower bounds values were 16% (13%-28%) for IDH-mutant and 572% (554%-999%) for IDH wild type tumors. The time between MR spectroscopy and surgery was longer for low-grade than for high-grade gliomas (P = .03), yet the time between MR spectroscopy and WHO diagnosis did not differ between grades (P = .07), possibly reflecting molecular analyses-induced delays in high-grade gliomas.

Conclusions: Our results, acquired in a clinic setting, confirmed that edited MR spectroscopy is highly specific for both IDH-mutation and 1p/19q-codeletion predictions and can provide a faster prognosis stratification. In the upcoming IDH-inhibitor treatment era, incorporation of edited MR spectroscopy into clinical workflow is desirable.

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在临床实践中采用编辑磁共振成像技术可改善对 IDH 突变胶质瘤患者的治疗。
背景和目的:异柠檬酸脱氢酶(IDH)突变和1p/19q编码缺失将成人型弥漫性胶质瘤分为三种预后不同的肿瘤亚型。我们的目的是通过对 D-2-羟基戊二酸(2HG)和胱硫醚进行定量,评估编辑磁共振波谱(MRS)在临床环境中对胶质瘤亚型划分的性能。此外,还对这种无创分类与综合组织分子分析之间的延迟进行了量化:对符合手术条件的推测为低级别胶质瘤的受试者(群组 1)和曾接受过治疗且病情进展的 IDH 突变胶质瘤受试者(群组 2)进行了前瞻性检查,在 3 T 下使用单体梅舍尔-加伍德点分辨光谱序列。克拉梅尔-拉奥下限(CRLB)阈值设定为 20%。根据 2021 年世界卫生组织分类进行的综合组织分子分析被视为基本事实:连续 34 名受试者参加了研究。由于光谱质量差和缺乏组织学标本,对 26 名受试者的数据进行了分析。21 人属于第一组(11 名女性;中位年龄:42 岁),5 人属于第二组(3 名女性;中位年龄:48 岁)。编辑的 MRS 对检测 IDH 突变的特异性为 100%,对预测 1p/19q 编码缺失状态的特异性为 91%。预测 IDH 和 1p/19q 编码缺失的灵敏度分别为 62% 和 33%。IDH突变型肿瘤的中位CRLB值为14%(13 - 32),IDH凋亡型肿瘤的中位CRLB值为572%(554 - 999)。低级别胶质瘤的MRS和手术之间的时间长于高级别胶质瘤(p = .03),但MRS和WHO诊断之间的时间在级别之间没有差异(p = .07),这可能反映了分子分析在高级别胶质瘤中引起的延迟:我们在临床环境中获得的结果证实,编辑的MRS对IDH突变和1p/19q编码缺失的预测具有高度特异性,能更快地进行预后分层。在即将到来的IDH抑制剂治疗时代,将编辑的MRS纳入临床工作流程是可取的:缩写:2HG = D-2-羟基戊二酸;Cth = 胱硫醚。CRLB:Cramér-Rao 下限;IDH:异柠檬酸脱氢酶。
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