Glioblastoma (GBM)

Glioblastoma is the most common and fastest-growing malignant brain tumor in adults. It arises from brain support cells and is the highest grade (Grade 4) brain tumor. It grows very rapidly, invades surrounding brain tissue, and promotes new blood vessel formation. With current treatments, median survival is approximately 15-21 months. Patients with MGMT gene methylation may have better outcomes. Each patient is unique; younger age, good performance status, extent of tumor resection, and presence of MGMT methylation are associated with more favorable prognosis.

Symptoms vary depending on tumor location, but most common include: severe headache (worse in morning, unresponsive to analgesics), nausea-vomiting (especially in morning), seizures (first symptom in some patients), unilateral arm-leg weakness, speech disturbance, personality changes, memory loss, visual disturbances, balance problems, and excessive sleepiness. Symptoms typically develop over weeks to months and progress rapidly. If experiencing one or more of these symptoms, consult a neurosurgeon and obtain a brain MRI.

The first step is obtaining a contrast-enhanced brain MRI. Typical MRI findings include a ring-enhancing mass with central necrosis. Advanced MRI techniques evaluate tumor behavior. Definitive diagnosis is established by microscopic examination of tissue obtained surgically; microscopy reveals dense cellular proliferation, neovascularization, and necrotic areas. Today, genetic/molecular testing is integral to diagnosis: IDH gene analysis, MGMT gene methylation status indicating chemotherapy response, and other genetic alterations are evaluated. These tests are essential for treatment selection and prognosis estimation.

Treatment consists of three main phases: 1) Surgery: as much tumor as possible is safely resected; modern techniques (fluorescent dyes, intraoperative MRI, neuronavigation, awake craniotomy) are used. Greater tumor resection positively affects survival. 2) Concurrent chemoradiation: begins 2-4 weeks after surgery, lasts approximately 6 weeks (radiation therapy + daily temozolomide). 3) Adjuvant chemotherapy cycles: typically 6-12 cycles of temozolomide administered after a treatment break. Electrical field therapy device can be added. Upon recurrence, repeat surgery, focal radiation therapy, alternative chemotherapy, or novel immunotherapy approaches are considered.

MGMT is a gene responsible for DNA repair in tumor cells. When this gene is 'silenced' (methylated), tumor cells cannot repair DNA damage, making chemotherapy (temozolomide) more effective and potentially extending survival. Patients with MGMT methylation have longer median survival compared to those without it. Therefore, MGMT testing should be performed after surgery and treatment planned accordingly. Patients without methylation may benefit from earlier evaluation of alternative treatments and clinical trials.

5-ALA is a special medication taken orally a few hours before surgery. Tumor cells take up this drug and fluoresce pink-purple under special blue light during surgery; normal brain tissue does not fluoresce. This allows the surgeon to better visualize tumor margins and remove small tumor areas that are difficult to distinguish with the naked eye. Research shows this technique helps achieve greater tumor resection. The drug has minimal side effects; only avoidance of sunlight for one to two days after surgery is necessary. This method is widely used in modern glioblastoma surgery.

Glioblastoma surgery is among the most complex neurosurgical procedures, but can be performed safely in experienced hands. Modern techniques (neuronavigation, intraoperative MRI, fluorescent dyes, awake craniotomy, brain mapping) minimize risks. Potential complications include: bleeding, new neurological deficit (mostly temporary), infection, seizures, cerebral edema (controlled with medication), wound healing problems, and cerebrospinal fluid leakage. For tumors near speech and motor areas, awake craniotomy minimizes risks. Overall, the benefits of surgery outweigh the risks; greater tumor resection positively affects survival.

Glioblastoma typically recurs. Most patients develop recurrent tumor sometime after initial treatment. Upon recurrence, treatment is individualized based on patient performance status and tumor location-size: 1) Re-operation: feasible if patient is in good condition and tumor location is suitable. 2) Focal radiotherapy: for small, localized recurrences, high-dose single-fraction radiation can be delivered. 3) Alternative chemotherapy: drugs such as lomustine or bevacizumab; bevacizumab can reduce tumor and edema. 4) Clinical trials: CAR-T cell therapy and other novel immunotherapies are promising options.

CAR-T cell therapy is an advanced immunotherapy based on harvesting patient's own immune cells, reengineering them in the laboratory to target tumor cells. Recent publications show promising results in some patients, including tumor shrinkage. Treatment can be delivered via injection into cerebrospinal fluid. Side effects are manageable. Early-stage clinical trials are currently ongoing; it is not yet standard treatment. Eligible patients can be referred to clinical trials. Advances in this field are expected to contribute to glioblastoma treatment in coming years.

Maintaining quality of life during and after treatment is very important. Supportive care includes: 1) Corticosteroids (dexamethasone): reduce cerebral edema and pressure, alleviate headache; long-term use is avoided. 2) Antiepileptic drugs: given to patients with seizures (typically levetiracetam); prophylaxis not routinely given to seizure-free patients. 3) Pain management: analgesics as needed. 4) Antiemetics for nausea-vomiting. 5) Psychological support: depression and anxiety are common; support and treatment are beneficial. 6) Physical therapy and rehabilitation: for weakness and balance problems. 7) Palliative care: should be initiated from time of diagnosis. 8) Social support: patient support groups and family counseling are valuable.