Clinical and Genetic Features of Brainstem Glioma in Adults: A Report of 50 Cases in a Single Center

Abstract

Background and purpose: Brainstem gliomas (BSGs) in adults are rare brain tumors with dismal outcomes. The aim of this study was to determine the clinical and genetic features in a series of BSGs and their association with the prognosis.

Methods: Fifty patients who underwent a stereotactic biopsy between January 2016 and April 2018 at a single institution were collected. Data on clinicopathological characteristics were analyzed and factors associated with patient survival were identified using a Cox regression model.

Results: The median age at diagnosis was 55.5 years, and 62% of the patients were male. Glioblastoma (44%) accounted for the largest proportion of BSGs, and oligodendroglioma (2 of 50) was rarely encountered. The IDH mutation (6 of 44) occurred infrequently in astrocytomas, and IDH-mutant tumors harbored both ATRX loss and MGMT promoter methylation at a relatively low level. Wild-type IDH astrocytomas were identified as having high rates of 1p/19q codeletion (5 of 38) and loss of heterozygosity 1p (8 of 38) or 19q (8 of 38) only. In diffuse midline glioma H3K27M mutant, MGMT promoter methylation occurred in three of four cases. Patients were offered radiotherapy and/or concurrent/adjuvant temozolomide chemotherapy, and their median survival time was 13 months. Multivariate analysis revealed that a low tumor grade, absence of tumor enhancement, duration of symptoms ≥3 months, Karnofsky performance status ≥70, and ATRX loss conferred a survival advantage.

Conclusions: Adult BSGs showed different molecular genetic characteristics, but also resembled supratentorial gliomas in their clinical features associated with oncological outcomes.

Keywords: brain stem neoplasms; glioma; molecular epidemiology; prognosis.

Fig. 1. Common genetic alterations detected in BSGs. The proportion of each genetic alteration is shown for different BSG subtypes. AA: anaplastic astrocytoma, BSG: brainstem glioma, DA: diffuse astrocytoma, DMLG: diffuse midline glioma, GBM: glioblastoma, O: oligodendroglioma, PA: pilocytic astrocytoma.

Fig. 2. Clinicopathological factors associated with OS of brainstem glioma patients. Kaplan-Meier curves were used to analyze the relationships of age, KPS, tumor grade, tumor enhancement, duration of symptoms, PTEN mutation, and ATRX loss with the OS of all patients. OS: overall survival, KPS: Karnofsky performance status.