Malignant gliomas are aggressive brain tumors that originate from the supportive cells of the central nervous system known as glial cells. These cancers are particularly challenging due to their highly invasive nature and tendency to rapidly infiltrate healthy brain tissue. Immediate and comprehensive medical intervention involving multiple disciplines is necessary to manage the disease.
Understanding Malignant Glioma
Gliomas are tumors that develop from glial cells, which normally support neurons in the brain and spinal cord. Malignant tumors are cancerous, characterized by swift, uncontrolled cell division. These high-grade gliomas are infiltrative, making complete surgical removal exceptionally difficult.
Malignant gliomas are categorized by the World Health Organization (WHO) into high-grade classifications, primarily Grade III and Grade IV, based on how abnormal the cells appear and how quickly they are expected to grow. The most aggressive and common type in adults is Glioblastoma (GBM), classified as a Grade IV tumor. Other high-grade types include anaplastic astrocytoma and anaplastic oligodendroglioma, typically designated as Grade III.
Recognizing Initial Manifestations
Symptoms of a malignant glioma arise from two primary mechanisms: generalized pressure within the skull and localized disruption of specific brain functions. Generalized symptoms occur as the tumor mass and associated swelling, known as cerebral edema, increase intracranial pressure. This can manifest as a persistent, worsening headache, often most severe in the morning, sometimes accompanied by nausea or vomiting.
Focal symptoms depend on the brain region where the tumor is located. A new-onset seizure is a common initial sign, occurring because the tumor irritates the surrounding brain tissue and disrupts normal electrical activity. Tumors in the motor or sensory cortex may cause progressive weakness or numbness on one side of the body.
If the tumor affects the frontal or temporal lobes, patients may experience difficulties with speech, language comprehension, or cognitive changes like memory loss or confusion. Changes in personality, mood swings, or a decline in executive function can also be early indicators. Visual disturbances, such as blurred or double vision, can occur if the tumor is pressing on the optic pathways or the visual processing center.
Clinical Confirmation and Grading
The diagnostic process begins with a neurological examination and imaging studies to confirm the presence of a mass. Magnetic Resonance Imaging (MRI) is the gold standard, providing high-resolution images that show the tumor’s size, location, and extent of infiltration. Computerized Tomography (CT) scans may be used for initial screening or in emergency situations, but they lack the detail necessary for definitive treatment planning.
A definitive diagnosis and grading require a tissue sample, obtained either through a stereotactic biopsy or during surgical resection. Analysis of this tissue determines the tumor’s WHO grade based on cellular characteristics such as mitotic activity and the presence of necrosis. Modern diagnosis also relies heavily on molecular markers, which provide information about the tumor’s underlying biology and significantly impact prognosis.
The status of the Isocitrate Dehydrogenase (IDH) gene mutation is an important molecular marker. IDH-mutant gliomas generally have a better prognosis and are classified differently than IDH-wildtype counterparts, which include most glioblastomas. Other molecular markers include the 1p/19q co-deletion, characteristic of oligodendrogliomas, which predicts a better response to certain chemotherapies. The methylation status of the MGMT promoter gene is also assessed, as methylation predicts a greater benefit from Temozolomide.
Primary Treatment Modalities
The initial management of malignant glioma follows a standardized approach involving a combination of surgery, radiation, and chemotherapy. The first step, when feasible, is surgical resection, with the primary goal of achieving maximal safe removal of the tumor mass. Removing as much of the tumor as safely possible can immediately alleviate symptoms from mass effect and improve the effectiveness of subsequent treatments.
Following surgery, the patient typically undergoes a concurrent phase of radiation therapy and chemotherapy. Radiation therapy is delivered as fractionated focal irradiation, usually totaling 60 Gray (Gy) delivered in daily 2 Gy fractions over six weeks. This high-energy treatment is precisely targeted to the tumor bed and surrounding tissue to destroy remaining cancer cells.
Chemotherapy in this concurrent phase utilizes the oral alkylating agent Temozolomide (TMZ), administered daily throughout the six weeks of radiation. TMZ works by damaging the DNA of rapidly dividing cancer cells, enhancing the effect of the radiation. After a short break, the patient transitions to the adjuvant phase, where TMZ is given alone in higher, pulsed doses for five days during a 28-day cycle, typically for six cycles. This standard tri-modality regimen increases overall survival compared to radiation alone.
Advanced and Supportive Care
Beyond the initial standard protocol, advanced therapies and supportive care strategies address recurrence, resistance, and quality of life.
Advanced Therapies
Tumor Treating Fields (TTF), delivered by a portable device that creates low-intensity alternating electric fields, is an advanced physical therapy used alongside maintenance chemotherapy to disrupt cancer cell division. For recurrent disease or resistance, molecularly targeted therapies, which block specific proteins that drive cancer growth, are investigated based on the patient’s genetic markers. Clinical trials offer access to cutting-edge strategies like immunotherapy, which aims to harness the patient’s own immune system to fight the cancer. Examples include CAR T-cell therapy and oncolytic virotherapy, which uses modified viruses to selectively destroy tumor cells.
Supportive Care
Supportive care focuses on minimizing symptoms and maintaining function. Cerebral edema, the swelling that causes headaches and neurological deficits, is managed using corticosteroids, most commonly Dexamethasone. Dexamethasone is administered to reduce swelling, though its use is monitored due to potential side effects.
Seizures, which affect many glioma patients, are controlled with anti-epileptic drugs (AEDs). Newer-generation AEDs like Levetiracetam are often preferred because they have fewer drug-to-drug interactions with chemotherapy agents. Physical, occupational, and speech therapy are also integral components, addressing functional deficits to maximize the patient’s independence and quality of life.