Faraj Christina Abi, McCutcheon Ian E, Gubbiotti Maria A, Perni Subha, Gule-Monroe Maria K, Akdemir Kadir, Clark Victoria E, Bander Evan D, Loghin Monica E, Prabhu Sujit S, Lang Frederick F, Weinberg Jeffrey S
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Department of Neuropathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
J Neurooncol. 2025 May;173(1):193-204. doi: 10.1007/s11060-025-04977-3. Epub 2025 Mar 6.
Extra-central nervous system metastasis (ECM) from glioblastoma and other high-grade gliomas (HGGs) is exceedingly rare, likely due to central nervous system barriers and the short overall survival (OS) in HGG patients, limiting the timeframe for metastasis. Improved treatments have extended survival, potentially increasing ECM incidence, though mechanisms remain unclear.
This retrospective study examines HGG patients (n = 16) with ECM treated at The University of Texas M. D. Anderson Cancer Center from 1993 to 2023.
Median age at HGG and ECM diagnoses were 33.6 and 35.1 years, respectively, with a slight female predominance. Diagnoses included glioblastoma, IDH-wildtype WHO Grade 4 (n = 11), epithelioid glioblastoma WHO Grade 4 (n = 2), astrocytoma IDH-mutant WHO Grade 4 (n = 2), and H3K27-altered diffuse midline glioma (n = 1). Median interval from HGG to ECM diagnosis was 10 months. The temporal lobe was the most common HGG site, with ECM primarily in cervical lymph nodes, bone, parotid gland, and cranial soft tissues. Genomic profiling identified TP53, EGFR, RB1, NF1, TERT promoter, and BRAF V600E mutations. Median OS from HGG diagnosis was 23.4 months, and median OS following ECM diagnosis was 5.9 months. Chemotherapy and radiotherapy to ECM sites extended survival. Leptomeningeal disease was present in 50% of cases and correlated with worse prognosis. ECM typically developed in advanced disease stages.
This study highlights genomic alterations, management, and outcomes associated with ECM in HGG. Tumor spread may stem from neurosurgical manipulation and occur via hematogenous and/or lymphatic routes. Multimodal treatment extends survival. Targeted therapies based on molecular profiles should be explored.
胶质母细胞瘤和其他高级别胶质瘤（HGG）发生中枢神经系统外转移（ECM）极为罕见，可能是由于中枢神经系统屏障以及HGG患者总体生存期（OS）较短，限制了转移发生的时间范围。尽管机制尚不清楚，但改进的治疗方法延长了生存期，可能会增加ECM的发生率。
这项回顾性研究调查了1993年至2023年在德克萨斯大学MD安德森癌症中心接受治疗的16例发生ECM的HGG患者。
HGG和ECM诊断时的中位年龄分别为33.6岁和35.1岁，女性略占优势。诊断包括胶质母细胞瘤、异柠檬酸脱氢酶（IDH）野生型WHO 4级（n = 11）、上皮样胶质母细胞瘤WHO 4级（n = 2）、IDH突变型星形细胞瘤WHO 4级（n = 2）和H3K27改变的弥漫性中线胶质瘤（n = 1）。从HGG诊断到ECM诊断的中位间隔时间为10个月。颞叶是最常见的HGG部位，ECM主要发生在颈部淋巴结、骨骼、腮腺和颅骨软组织。基因谱分析确定了TP53、表皮生长因子受体（EGFR）、视网膜母细胞瘤蛋白1（RB1）、神经纤维瘤病1型（NF1）、端粒酶逆转录酶（TERT）启动子和BRAF V600E突变。从HGG诊断开始的中位OS为23.4个月，ECM诊断后的中位OS为5.9个月。对ECM部位进行化疗和放疗可延长生存期。50%的病例存在软脑膜疾病，且与预后较差相关。ECM通常在疾病晚期发生。
本研究强调了与HGG中ECM相关的基因改变、治疗和结局。肿瘤扩散可能源于神经外科手术操作，并通过血行和/或淋巴途径发生。多模式治疗可延长生存期。应探索基于分子特征的靶向治疗。
