Extracranial Metastasis from High-grade Glioma: A Single-institution Experience

Introduction: Extracranial metastasis (ECM) from glioblastoma and other high-grade gliomas (HGGs) is exceedingly rare, likely due to the unique barriers of the central nervous system 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.

Methods: 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.

Results: 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 CNS WHO grade 4 (n=11), epithelioid glioblastoma CNS WHO grade 4 (n=2), astrocytoma IDH-mutant CNS 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 and bone, followed by the parotid gland and cranial soft tissues. Genomic profiling identified TP53, EGFR, RB1, NF1, TERT promoter, and BRAFV600E mutations. Standard HGG treatments (surgery, chemotherapy, and radiotherapy) were administered in most cases. Treatment of local HGG recurrence and ECM varied, but still included surgery, radiotherapy, and chemotherapy, alone or combined. Median OS from HGG diagnosis was 23.4 months, and median OS following ECM diagnosis was 5.9 months. Treatment of ECM with chemotherapy and radiotherapy extended OS. Leptomeningeal disease was found in 50% of cases and correlated with poorer prognosis. ECM typically developed in advanced disease stages.

Conclusion : This study highlights genomic alterations, management, and outcomes associated with ECM in HGG. Tumor spread may be attributed to neurosurgical intervention and may follow hematogenous and/or lymphatic routes. Multimodal treatment appears to extend survival. Targeted therapies based on molecular profiles should be considered. Further research is essential to elucidate ECM's molecular basis and improve outcomes.