Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, China.
Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, China.
Ann Nucl Med. 2021 Apr;35(4):493-503. doi: 10.1007/s12149-021-01589-5. Epub 2021 Feb 2.
Isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation and O-methylguanine-DNA methyltransferase (MGMT) promoter methylation status are diagnostic, prognostic, predictive and therapeutic biomarkers for primary diffuse gliomas, and this study aimed to explore the relationship between choline (CHO) positron emission tomography (PET) parameters and these molecular alterations.
Twenty-eight patients who were histopathologically diagnosed with primary diffuse glioma and underwent presurgical CHO PET/CT were retrospectively analyzed, and IDH, TERT and MGMT alterations were examined. The volume of interest (VOI) was semiautomatically defined based on standardized uptake value (SUV) thresholds, and 5 traditional CHO parameters, namely, SUVmax, SUVmean, metabolic tumor volume (MTV), total lesion CHO uptake (TLC) and tumor-to-normal contralateral cortex activity ratio (T/N ratio), were calculated. Wilcoxon rank-sum tests and receiver operating characteristic (ROC) curves were applied to evaluate the differences and performances of the CHO parameters, and their capability to stratify patient prognosis was also evaluated.
All 5 parameters were significantly higher in IDH-wildtype gliomas than in IDH-mutant gliomas (p = 0.0001-0.037), and SUVmax, SUVmean, TLC and the T/N ratio exhibited good performances in distinguishing the IDH status (areas under the ROC curve (AUCs) 0.856-0.918, accuracies 0.857-0.893) as well as stratifying patient prognosis. Although the differences and performances of the traditional parameters in distinguishing diverse TERT and MGMT statuses were moderate in the whole population, the T/N ratio and TLC displayed certain predictive value in discriminating the TERT status in the IDH-mutant and IDH-wildtype subgroups (p = 0.028-0.048, AUCs 0.857-0.860, accuracies 0.800-0.917, respectively).
Traditional CHO PET parameters are capable of distinguishing IDH but not TERT or MGMT alterations in the whole population. In accordance with the clinical understanding of TERT promoter mutations, the T/N ratio and TLC can also discriminate the TERT status in IDH subgroups.
异柠檬酸脱氢酶（IDH）突变、端粒酶逆转录酶（TERT）启动子突变和 O-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）启动子甲基化状态是原发性弥漫性神经胶质瘤的诊断、预后、预测和治疗生物标志物，本研究旨在探讨胆碱（CHO）正电子发射断层扫描（PET）参数与这些分子改变之间的关系。
回顾性分析 28 例经组织病理学诊断为原发性弥漫性神经胶质瘤且接受术前 CHO PET/CT 检查的患者，检测 IDH、TERT 和 MGMT 改变。基于标准化摄取值（SUV）阈值半自动定义感兴趣区（VOI），计算 5 种传统 CHO 参数，即 SUVmax、SUVmean、代谢肿瘤体积（MTV）、总病变 CHO 摄取量（TLC）和肿瘤-对侧正常皮质活性比（T/N 比）。采用 Wilcoxon 秩和检验和受试者工作特征（ROC）曲线评估 CHO 参数的差异和性能，并评估其患者预后分层能力。
在 IDH 野生型神经胶质瘤中，所有 5 个参数均显著高于 IDH 突变型神经胶质瘤（p=0.0001-0.037），SUVmax、SUVmean、TLC 和 T/N 比在区分 IDH 状态方面表现出良好的性能（ROC 曲线下面积（AUC）0.856-0.918，准确率 0.857-0.893），并分层患者预后。尽管在整个人群中，传统参数区分不同 TERT 和 MGMT 状态的差异和性能中等，但 T/N 比和 TLC 在区分 IDH 突变和 IDH 野生型亚组的 TERT 状态方面具有一定的预测价值（p=0.028-0.048，AUC 0.857-0.860，准确率 0.800-0.917，分别）。
传统的 CHO PET 参数能够区分 IDH，但不能区分整个人群中的 TERT 或 MGMT 改变。根据 TERT 启动子突变的临床认识，T/N 比和 TLC 也可以区分 IDH 亚组中的 TERT 状态。
