Glioblastoma: Aggressive Brain Tumor - Current Research & Hope

What is Glioblastoma?

Glioblastoma (GBM), now formally termed ‘glioblastoma, IDH-wildtype’ in the WHO 2021 classification, is the most common and aggressive type of diffuse astrocytic tumour in adults. It arises from astrocytes, the star-shaped cells that support and nourish neurons in the brain and spinal cord. As a grade IV tumour, glioblastoma grows rapidly, invading nearby brain tissue and disrupting vital functions. Symptoms often develop quickly due to the tumour's fast growth and ability to affect various parts of the brain.

Glioblastoma accounts for approximately 14–15% of all primary brain tumours and about 48% of malignant CNS tumours, with peak incidence between ages 55 and 75. Despite progress in glioblastoma treatment, despite multimodal therapy, prognosis remains poor, with a median overall survival of 14–16 months and 5-year survival below 7%.

Types of Glioblastoma

• Primary (de novo) glioblastoma: This is the most common form, developing rapidly without evidence of a less malignant precursor lesion. It typically occurs in older adults.
• Secondary glioblastoma: This term was used in older classifications to describe high-grade transformation of IDH-mutant astrocytomas; in the WHO 2021 system, such tumours are now classified as astrocytoma, IDH-mutant, Grade 4 and progresses over time. It is more often found in younger patients.
• Molecular subtypes: Molecular profiling historically identified four transcriptomic subtypes (classical, proneural, mesenchymal, and neural). However, current WHO practice focuses on IDH mutation, TERT promoter, EGFR amplification, and +7/−10 chromosome signatures to define glioblastoma

Causes and Risk Factors

• Genetic mutations in genes such as EGFR, PTEN, TP53, and IDH1/2
• Age: Most commonly diagnosed in people over 60
• Gender: Slightly more common in males
• Previous radiation therapy to the brain
• Family history of gliomas or certain genetic syndromes

Note: The causes of glioblastoma remain unclear in most cases, and no direct environmental or lifestyle links have been established.

Signs & Symptoms of Glioblastoma

• Headaches
• Seizures
• Nausea and vomiting
• Drowsiness or lethargy
• Personality or behavioural changes
• Weakness or numbness (often on one side of the body)
• Memory loss
• Speech or language difficulties
• Vision changes

It's important to note that these glioblastoma symptoms can also be caused by other conditions. If you experience any of these symptoms persistently, it's crucial to consult a healthcare professional for an accurate diagnosis.

According to the World Health Organization (WHO) classification of CNS tumours, glioblastoma is a Grade 4 tumour, the most aggressive type of brain cancer. Grade 4 tumours grow rapidly, spread quickly, and have a high risk of recurrence, making them the most severe and fast-growing among CNS tumours.

How Glioblastoma is Diagnosed?

1. Neurological exam: Checks done on vision, hearing, balance, coordination, strength, and reflexes to identify which part of the brain may be affected.
2. Imaging tests: MRI is the main tool to locate and measure the tumour. Sometimes a contrast dye is used for clearer images. CT or PET scans may also be used.
3. Biopsy: A small tissue sample is taken with a needle or during brain tumour surgery to confirm cancer and identify glioblastoma cells.

Diagnostic Tests for Glioblastoma

• Magnetic Resonance Imaging (MRI): The preferred imaging method for visualising glioblastoma, typically using contrast-enhanced T1-weighted and FLAIR sequences to assess tumour margins and edema.
• Computed Tomography (CT) scan: Helps detect tumours if MRI is unavailable or contraindicated.
• Biopsy or surgical resection: Confirms the diagnosis by examining tumour tissue under a microscope.
• Molecular and genetic testing: Molecular testing includes evaluation of IDH mutation, MGMT promoter methylation, EGFR amplification, and TERT promoter mutation, which provide diagnostic and prognostic information

Important Fact:

After a glioblastoma diagnosis, doctors perform molecular and genetic tests on the tumour. They check for features like IDH status to understand how the tumour may grow and respond to treatment. This information helps personalize treatment plans for the best possible care.

Treatment Options

Glioblastoma treatment typically involves a combination of surgery, radiation, and chemotherapy to maximise tumour control and improve quality of life. The specific approach depends on factors such as tumour size, location, genetic characteristics, and the patient's overall health.

1. Surgery

The first step in treating glioblastoma is usually brain tumour surgery to remove as much of the tumour as possible without damaging critical brain areas. Complete removal is often impossible due to the tumour's infiltrative nature, but even partial removal can help reduce symptoms and improve outcomes.

2. Radiotherapy

After surgery, radiation therapy is used to target any remaining cancer cells. Radiotherapy is typically delivered over several weeks and plays a crucial role in improving survival for patients with GBM.

3. Chemotherapy

The standard chemotherapeutic agent is temozolomide, administered concurrently with radiotherapy and followed by adjuvant cycles (the Stupp protocol). It works by damaging the DNA of tumour cells, slowing or stopping their growth.

4. Tumour Treating Fields (TTF)

Tumour Treating Fields (TTF) are a non-invasive adjunct therapy delivering alternating electric fields via scalp electrodes to disrupt mitosis in tumour cells. When used with temozolomide, TTF has shown improved progression-free and overall survival, delivered through electrodes placed on the scalp, to disrupt cancer cell division. It is typically used in combination with other therapies.

5. Clinical Trials & Emerging Therapies

• Targeted therapies (e.g., drugs aimed at specific genetic mutations)
• Immunotherapy (stimulates the patient's immune system to attack cancer)
• Gene therapy (experimental approaches to correct tumour-causing mutations)
• Novel drug delivery methods (e.g., nanoparticles, convection-enhanced delivery)

Prognosis and Survival Rates

Despite advances in treatment, glioblastoma generally has a poor prognosis. The median survival is about 14–15 months with current standard treatment (surgery, radiotherapy, and chemotherapy). Only a small percentage of patients survive more than five years after diagnosis. Prognosis is influenced by factors such as age, tumour genetics, extent of surgical resection, and overall health.

Important Fact:

According to American Association of Neurological Surgeons (AANS), glioblastoma is the most common malignant brain tumour, making up nearly 48% of all CNS cancers. It occurs in about 3.2 people per 100,000 each year. The median age at diagnosis is 64, and it is more common in men than women. Unfortunately, the prognosis is poor, with around 40% of patients surviving the first year after diagnosis and only 17% surviving the second year.

Coping and Support

• Access to counselling and psychological support
• Support groups for patients and families
• Palliative care for symptom relief and quality of life
• Rehabilitation services (physical, occupational, speech therapy)
• Social work and practical support resources
• Information and advocacy from reputable organizations

Preventive Measures & Research Outlook

• There are currently no known preventive measures for glioblastoma, as most cases arise sporadically without identifiable environmental or lifestyle triggers
• Ongoing research focuses on:
  • Understanding genetic and environmental factors
  • Developing targeted and personalized therapies
  • Improving early detection methods
  • Expanding clinical trials for new treatments

Conclusion

Glioblastoma (GBM) is one of the most aggressive brain tumours, making early diagnosis and comprehensive care essential. Advances in glioblastoma treatment, including surgery, radiotherapy, chemotherapy, Tumour Treating Fields (TTF), and emerging therapies, offer hope for better outcomes and symptom management. Managing glioblastoma symptoms and maintaining quality of life requires a personalised, multidisciplinary approach.

If you or a loved one is affected, consulting a healthcare professional is crucial to determine the best treatment plan. Metropolis Healthcare provides advanced diagnostic services for brain tumours, including NABL and CAP accredited labs, at-home sample collection, and fast results via the Metropolis App. With nationwide coverage and expert care, they help patients make informed decisions and stay proactive in managing glioblastoma.

FAQs

What causes glioblastoma?

Most cases of glioblastoma are caused by random genetic mutations in brain cells rather than inherited factors. Known risk factors like prior radiation to the head, certain genetic syndromes, and older age are implicated, but most cases have no identifiable cause.

Can glioblastoma be cured?

Currently, glioblastoma cannot be cured with existing treatments. Standard therapies can temporarily control the disease and improve symptoms, but recurrence is almost inevitable.

How long do patients with glioblastoma survive?

The median survival for patients with GBM is about 14–15 months, even with the best available therapies. Some younger patients with favourable genetic markers and extensive tumour removal may live longer.

Are there any new treatments for glioblastoma?

Yes, several promising treatments are being actively researched and are available in some clinical trials. These include Tumour Treating Fields (TTF), targeted molecular therapies, immunotherapy, and gene therapy. While not yet standard, these approaches offer hope for improved outcomes in the future.

Can lifestyle changes prevent glioblastoma?

There are no proven lifestyle changes shown to prevent glioblastoma due to its largely genetic and unmodifiable risk factors.

References

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