What is the significance of glioblastoma?

The Significance of Glioblastoma

Glioblastoma is the most lethal primary brain tumor with extremely poor prognosis, with only one-third of patients surviving for 1 year and fewer than 5% living beyond 5 years. 1

Epidemiology and Impact

Glioblastoma (WHO grade IV astrocytoma) is the most common and aggressive form of primary malignant brain tumors in adults, accounting for:

• 54% of all gliomas 1
• 45% of all malignant primary CNS tumors 1
• Annual incidence of 5-7 per 100,000 population 1

The disease has profound mortality implications:

• Median survival of only 14-16 months with standard treatment 1
• 1-year survival rate of approximately 33% 1
• 5-year survival rate below 5% 1

Clinical Presentation and Pathophysiology

Glioblastomas typically present with:

• Symptoms of increased intracranial pressure
• Seizures
• Focal neurologic deficits related to tumor location and peritumoral edema 1

Key pathological features include:

• Diffuse infiltration into surrounding tissues
• Frequent crossing of midline to involve contralateral brain
• Considerable edema and mass effect
• Strong contrast enhancement on imaging (96% of cases) 1
• Tumor cells found in peritumoral edema corresponding to T2-weighted MRI abnormalities 1

Prognostic Factors

The most important prognostic factors include:

• Histologic diagnosis
• Age (younger age is favorable)
• Performance status (KPS score)
• Extent of surgical resection 1

Additional adverse factors:

• Tumor size larger than 6 cm
• Tumor crossing midline
• Significant preoperative neurologic deficits
• Wild-type IDH1 or IDH2 1

Standard Treatment Approach

The current standard of care involves a multimodal approach:

1. Maximal safe surgical resection when feasible (improves survival compared to biopsy alone) 1
2. Fractionated external beam radiotherapy (60 Gy in 30 fractions) 1
3. Concurrent and adjuvant temozolomide chemotherapy (significantly improves median and 2-year survival) 1, 2

For elderly patients or those with poor performance status, shorter hypofractionated radiation regimens may be used 1.

Treatment Challenges

Several factors contribute to the poor prognosis:

• Infiltrative nature makes complete surgical resection difficult 1
• Nearly universal recurrence despite aggressive treatment 1
• Blood-brain barrier limits drug delivery 1
• Tumor heterogeneity contributes to treatment resistance 3
• Limited effective therapeutic options for recurrent disease 1

Recent Advances and Future Directions

Despite extensive research, treatment options remain limited:

• Tumor-treating fields (TTFields) may provide modest benefit but remain controversial 1
• Bevacizumab may be used for recurrent disease but doesn't improve overall survival 1
• Immunotherapy approaches have shown limited success to date 4
• Molecular profiling (including IDH mutation status) is improving classification and may guide future targeted therapies 5

Clinical Implications

The devastating impact of glioblastoma extends beyond survival statistics:

• Significant neurological morbidity affecting quality of life
• High symptom burden requiring supportive care
• Substantial caregiver burden
• Limited effective treatment options at recurrence
• Need for multidisciplinary care throughout the disease course

Glioblastoma remains one of the most challenging cancers to treat, with minimal improvements in outcomes despite decades of research, highlighting the urgent need for more effective therapeutic approaches.