Glioblastoma (GBM)

Glioblastoma is the most common and fastest-growing malignant brain tumor in adults. It originates from glial support cells of the brain and is classified as Grade 4 (highest grade) according to World Health Organization classification. It grows very rapidly, infiltrates surrounding brain tissue, and promotes new blood vessel formation. With modern treatments, median overall survival is 15-21 months, with 2-year survival rate of 26% and 5-year survival rate of 5-7%. Patients with MGMT gene methylation have better prognosis (21-24 months). Each patient is unique; favorable prognostic factors include young age, good performance status, ability to achieve gross total resection, and positive MGMT methylation status.

Glioblastoma symptoms vary depending on tumor location but most common symptoms include: Severe headache (worse in morning, unresponsive to pain medication), nausea-vomiting (especially in morning), epileptic seizures (initial symptom in 20-30% of cases), unilateral arm-leg weakness, speech disturbances, personality changes, memory loss, vision disturbances, balance problems, and excessive drowsiness. Symptoms typically develop over weeks to months and progress rapidly. If experiencing any of these symptoms, immediate consultation with a neurosurgeon and brain MRI is essential.

Glioblastoma diagnosis begins with contrast-enhanced brain MRI. Typical MRI findings include thick ring-shaped contrast enhancement with central area of necrosis. Advanced MR techniques (perfusion, spectroscopy) demonstrate tumor blood flow and metabolism. Definitive diagnosis is established by histopathological examination of tissue obtained during surgery. Molecular testing is now mandatory: IDH gene (lack of mutation indicates GBM), MGMT gene methylation (predicts chemotherapy response), EGFR and TERT mutations are evaluated. These tests are critical in determining treatment planning and prognosis.

Glioblastoma treatment consists of three main phases: 1) Surgery: Safe maximal resection of tumor using modern techniques (5-ALA fluorescence, intraoperative MRI, awake craniotomy). 2) Concurrent chemoradiotherapy: 6 weeks of radiotherapy plus temozolomide (Stupp protocol) starting 2-4 weeks after surgery. 3) Adjuvant chemotherapy: 6-12 cycles of temozolomide (12 cycles if MGMT methylated). Optune device with tumor-treating fields (TTFields) can be added. At recurrence, repeat surgery, stereotactic radiosurgery, bevacizumab, or novel immunotherapies (CAR-T) may be considered.

MGMT (O6-methylguanine-DNA methyltransferase) is a DNA repair gene. When MGMT gene is methylated (silenced), tumor cells become more sensitive to temozolomide chemotherapy because they cannot repair DNA damage. In MGMT-methylated patients, chemotherapy is much more effective, with median overall survival reaching 21-24 months (versus 12-15 months in unmethylated patients). Therefore, MGMT methylation testing is mandatory in all glioblastoma patients and treatment planning should be adjusted accordingly. Methylated patients are recommended 12 cycles of chemotherapy, while alternative treatments may be considered earlier in unmethylated patients.

5-ALA (5-aminolevulinic acid) is a medication taken orally by the patient 3 hours before surgery. Tumor cells take up this drug and fluoresce pink-purple color. During surgery under special blue light, the surgeon can visualize tumor cells very clearly and better distinguish the boundary between normal brain tissue and tumor. This allows 20-30% more tumor removal and extends survival by 2-3 months. 5-ALA fluorescence-guided surgery has become the gold standard in glioblastoma surgery. Side effects are minimal (sun protection required for 48 hours).

Glioblastoma surgery risks vary depending on tumor location. Overall complication rate is approximately 5-10%. Major risks include: Hemorrhage (2-3%), infection (1-2%), cerebral edema, seizure, arm-leg weakness (transient 10-15% if near motor cortex, permanent 2-5%), speech disturbance (5-10% if near language cortex), vision disturbance (if in occipital lobe). Modern techniques (intraoperative MRI, neuronavigation, awake craniotomy, motor-language mapping) minimize these risks. Working with experienced neurosurgery teams is critically important.

Glioblastoma almost always recurs because tumor cells infiltrate brain tissue and cannot be completely removed surgically. Median time to recurrence is 7-10 months. Treatment options for recurrence include: 1) Repeat surgery (if tumor is localized and patient is in good condition), 2) Stereotactic radiosurgery (for small recurrences), 3) Bevacizumab (Avastin) chemotherapy (inhibits angiogenesis), 4) Lomustine chemotherapy, 5) Clinical trial drugs and novel immunotherapies (CAR-T cell therapy, dendritic cell vaccines, oncolytic viruses). Treatment planning is individualized for each patient.

CAR-T cell therapy involves genetically modifying the patient's own immune cells (T cells) in the laboratory to recognize and attack tumor cells, then reinfusing them into the patient. CAR-T therapies for glioblastoma show very promising results in 2025-2026. EGFRvIII and IL13Rα2-targeted CAR-T therapies are being evaluated in clinical trials. It is not yet standard treatment but holds great promise. Some centers in Turkey also offer CAR-T therapy under clinical trial protocols. It may become an important option for recurrent glioblastoma patients.

Maintaining quality of life during glioblastoma treatment is very important. Recommendations include: 1) Regular exercise (walking, light gymnastics), 2) Balanced nutrition (increased protein and calorie needs), 3) Adequate sleep, 4) Stress management (meditation, yoga), 5) Social support (family, friends, support groups), 6) Symptom control (analgesics, antiepileptics, corticosteroids), 7) Psychological support (depression, anxiety treatment), 8) Physical therapy and rehabilitation (if weakness present), 9) Working with palliative care team. Each patient's needs are different and treatment plan should be adjusted accordingly.