What is the mechanism of death associated with glioblastoma (Glioblastoma Multiforme, GBM) in most cases?

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From the Guidelines

Death associated with glioblastoma (Glioblastoma Multiforme, GBM) is most commonly due to local tumor progression and increased intracranial pressure, rather than distant metastasis.

Mechanism of Death

  • The infiltrative nature of glioblastoma makes it difficult to achieve complete surgical resection, leading to local tumor recurrence and progression 1.
  • The tumor's location in the brain can cause increased intracranial pressure, cerebral edema, and herniation, ultimately leading to death 1.
  • The evidence suggests that glioblastoma is a highly lethal tumor, with a median survival of approximately 15 months, and a 2-year survival rate of 27% 1.

Treatment and Prognosis

  • The current standard treatment for glioblastoma includes maximal surgical resection, followed by radiation therapy and temozolomide chemotherapy 1.
  • The prognosis for glioblastoma patients depends on various factors, including tumor grade, histology, and molecular characteristics, such as MGMT promoter methylation status 1.
  • Patients with methylated MGMT promoter status tend to have a better prognosis and respond better to alkylating agent chemotherapy, such as temozolomide 1.

From the Research

Mechanism of Death in Glioblastoma

The mechanism of death associated with glioblastoma (Glioblastoma Multiforme, GBM) is multifactorial, involving various clinical factors and autopsy findings.

  • Key factors considered as potential causes of death include:
    • Herniation (axial, transtentorial, subfalcine, tonsillar)
    • Surgical complications (death within thirty days of surgery secondary to cerebral hemorrhage and/or edema)
    • Severe systemic illness
    • Brainstem invasion by tumor
    • Neutron-induced cerebral injury (cerebral and brainstem gliosis were evident in these cases) 2
  • A potential cause of death could be identified in 93% of patients, with herniation being a significant factor in 61% of patients, often accompanied by an additional identifiable cause of death 2

Clinical Factors and Autopsy Findings

Clinical factors and autopsy findings play a crucial role in understanding the mechanism of death in GBM patients.

  • Studies have shown that patients with no ante mortem diagnosis were likely to have herniated, whereas patients who underwent neutron irradiation were unlikely to have herniated 2
  • The time elapsed between the identification of metastasis and death was significantly increased in patients undergoing surgery, whereas the time from the diagnosis of the primary tumor to death was significantly increased in patients receiving radiation therapy 3

Molecular Mechanisms and Treatment Outcomes

Molecular mechanisms and treatment outcomes are essential in understanding the prognosis and survival of GBM patients.

  • Research has indicated that neuronal PD-L1 signaling in brain cells is important for GBM patient survival, and reciprocal PD-L1 regulation in tumor-adjacent brain tissue and tumor tissue could be a prognostic biomarker for GBM 4
  • The present therapies have been unable to improve life expectancy in patients, and current research is focused on investigating the role of pattern recognition and tyrosine kinase receptors in glioblastoma development and evolution, and their possible use to improve treatment outcomes and patient survival 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Metastasis from glioblastoma multiforme: a meta-analysis.

Revista da Associacao Medica Brasileira (1992), 2019

Research

PD-L1 expression by neurons nearby tumors indicates better prognosis in glioblastoma patients.

The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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