Department of Neurosurgery, Massachusetts General Hospital, Boston, MA.
Department of Neurosurgery, University of California San Diego, La Jolla, CA.
Blood. 2024 Sep 5;144(10):1093-1100. doi: 10.1182/blood.2024023832.
Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown cause. Participants underwent genotyping of CSF-derived DNA using a quantitative polymerase chain reaction-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF, and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma, and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7 of 33 cases (21.2%) of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median, 3 vs 12 days; P = .027). This assay was then implemented in a Clinical Laboratory Improvement Amendments environment, with 2-day median turnaround for diagnosis of CNS lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.
神经外科活检的延迟和风险妨碍了中枢神经系统 (CNS) 淋巴瘤和其他 CNS 肿瘤的及时诊断和治疗。我们前瞻性地将靶向性快速 CSF 基因分型整合到对 70 名 CNS 病变原因不明的患者的评估中。参与者使用基于定量聚合酶链反应的方法对 CSF 衍生 DNA 进行基因分型，以在 80 分钟内平行检测 MYD88、TERT 启动子、IDH1、IDH2、BRAF 和 H3F3A 基因中的单核苷酸变异。在肿瘤患者中检测到了 42%的典型突变，包括原发性和继发性 CNS 淋巴瘤、胶质母细胞瘤、IDH 突变型脑干胶质瘤和 H3K27M 突变型弥漫性中线胶质瘤。基因分型结果使 33 例新诊断肿瘤中的 7 例（21.2%）无需手术活检，从而显著加速了针对疾病的治疗的启动（中位数分别为 3 天和 12 天；P=0.027）。然后，该检测在临床实验室改进修正案环境中实施，在 4 个临床地点的 66 名患者中，诊断 CNS 淋巴瘤的中位周转时间为 2 天。我们的研究前瞻性地表明，靶向性快速 CSF 基因分型影响疑似 CNS 肿瘤的肿瘤学管理。
