Brain Cancer and Brain Tumors

Last updated: January 2025 | Medical Reviewer: Oncol.net Editorial Board

Overview

Brain tumors are abnormal growths of cells within the brain or skull. They can be classified as primary (originating in the brain) or metastatic (spread from cancer elsewhere in the body). Primary brain tumors arise from the various cell types that make up the brain and surrounding structures, including glial cells, neurons, meninges (brain coverings), and blood vessels.

Brain tumors affect approximately 24,000 people per year in the United States with primary malignant brain tumors, and an estimated 200,000 with metastatic brain tumors. They can occur at any age but are most common in children (second most common childhood cancer after leukemia) and older adults (peak incidence age 65-74). Outcomes vary dramatically based on tumor type, location, and grade.

Types of Brain Tumors

Primary Brain Tumors

Gliomas (50-60% of primary brain tumors)

Tumors arising from glial cells (supportive cells of the brain):

• Glioblastoma (GBM) - WHO Grade 4:
  • Most common and most aggressive primary brain tumor in adults (45-50% of malignant gliomas)
  • Median age at diagnosis: 64 years
  • Rapidly growing, infiltrative, cannot be completely removed surgically
  • Median survival: 12-18 months with treatment, 3-4 months without
  • IDH-wildtype (90%): More aggressive, older patients
  • IDH-mutant (10%): Better prognosis, younger patients, often evolved from lower-grade glioma
  • MGMT promoter methylation predicts better response to chemotherapy
• Astrocytoma - WHO Grades 2-3:
  • Grade 2 (low-grade): Slow-growing, median survival 5-10 years
  • Grade 3 (anaplastic): Faster-growing, median survival 2-5 years
  • IDH-mutant tumors have significantly better prognosis than IDH-wildtype
  • Most eventually progress to glioblastoma
• Oligodendroglioma - WHO Grades 2-3:
  • Arise from oligodendrocytes (cells that make myelin)
  • Characterized by 1p/19q codeletion (diagnostic marker)
  • More chemosensitive than astrocytomas
  • Better prognosis: median survival 10-15 years (Grade 2), 5-10 years (Grade 3)
  • Often present with seizures

Meningioma (30-35% of primary brain tumors)

• Arise from meninges (membranes covering brain and spinal cord)
• Typically benign (80-85% are WHO Grade 1)
• More common in women (2:1 ratio), average age 60
• Often discovered incidentally on imaging
• Slow-growing, can become very large before causing symptoms
• Treatment: Observation for small asymptomatic tumors, surgery for symptomatic or growing tumors
• Grade 2 (atypical, 15-20%): Higher recurrence risk
• Grade 3 (anaplastic, 1-3%): Malignant, aggressive, poor prognosis
• Radiation after surgery for incomplete resection or higher-grade tumors

Pituitary Adenomas (10-15% of primary brain tumors)

• Benign tumors of pituitary gland
• Functional (hormone-secreting): Cause endocrine symptoms
  • Prolactinoma (most common): Elevated prolactin, menstrual irregularities, galactorrhea
  • Growth hormone-secreting: Acromegaly (adults), gigantism (children)
  • ACTH-secreting: Cushing's disease
• Non-functional: Cause symptoms from mass effect (vision changes, headaches)
• Treatment: Medications (especially for prolactinomas), transsphenoidal surgery, radiation

Other Primary Brain Tumors

• Medulloblastoma: Most common malignant brain tumor in children, arises in cerebellum, treated with surgery + radiation + chemotherapy, 5-year survival 70-80%
• Ependymoma: Arises from ependymal cells lining ventricles, can occur in children or adults
• Craniopharyngioma: Benign but locally aggressive, near pituitary, causes hormone deficiencies
• Schwannoma (acoustic neuroma): Benign tumor of nerve sheath, commonly affects hearing nerve (cranial nerve VIII)
• Primary CNS lymphoma: Rare, more common in immunocompromised patients, treated with chemotherapy (methotrexate-based) + radiation

Metastatic Brain Tumors

Cancer that spreads to the brain from elsewhere in the body:

• 5-10 times more common than primary brain tumors
• Occur in 10-30% of adult cancer patients
• Most common primary sites:
  • Lung cancer (50%)
  • Breast cancer (15-20%)
  • Melanoma (10%)
  • Kidney cancer (5-10%)
  • Colorectal cancer (5%)
• Can be single or multiple lesions
• Treatment depends on number of lesions, primary cancer type, and systemic disease burden

Risk Factors

Established Risk Factors

• Ionizing radiation: Strongest known environmental risk factor
  • Previous radiation therapy to head (for other cancers, leukemia)
  • Atomic bomb exposure
  • High-dose radiation exposure in childhood increases risk most significantly
  • Diagnostic X-rays and CT scans: No clear association
• Genetic syndromes (account for <5% of brain tumors):
  • Neurofibromatosis type 1 (NF1): Optic pathway gliomas
  • Neurofibromatosis type 2 (NF2): Bilateral acoustic neuromas, meningiomas
  • Li-Fraumeni syndrome (TP53 mutation): Gliomas, medulloblastomas
  • Tuberous sclerosis: Subependymal giant cell astrocytomas
  • Von Hippel-Lindau disease: Hemangioblastomas
  • Lynch syndrome: Gliomas (modest increased risk)
• Family history: Small increased risk (2-fold) with first-degree relative with glioma
• Immunosuppression: Increased risk of primary CNS lymphoma (HIV, organ transplant recipients)

Not Risk Factors

• Cell phone use (extensive research shows no association)
• Power lines or electromagnetic fields
• Hair dye
• Artificial sweeteners (aspartame)
• Head trauma

Signs and Symptoms

Symptoms depend on tumor location, size, and rate of growth. Slowly growing tumors may be quite large before causing symptoms, while fast-growing tumors cause symptoms earlier.

General Symptoms (From Increased Intracranial Pressure)

• Headaches: Present in 50% of patients
  • Often worse in morning, improve after getting up
  • Worsened by coughing, straining, bending over
  • Different from typical headaches (new pattern or progressively worsening)
  • May be associated with nausea/vomiting
• Nausea and vomiting: Especially in morning, may be projectile
• Cognitive changes: Confusion, difficulty concentrating, memory problems
• Personality or mood changes: Depression, apathy, irritability
• Drowsiness or fatigue
• Vision changes: Blurred vision, double vision, loss of peripheral vision

Focal Neurological Symptoms (Location-Specific)

• Seizures: 30-50% of patients, often first symptom
  • New-onset seizures in adults should prompt brain imaging
  • Can be focal (one body part) or generalized
  • More common with slow-growing tumors (oligodendrogliomas, low-grade gliomas)
• Motor weakness: Weakness or paralysis of arm, leg, or face (hemiparesis)
• Sensory changes: Numbness, tingling, loss of sensation
• Speech difficulties: Aphasia (trouble finding words, understanding language)
• Visual field defects: Loss of vision in specific areas
• Coordination problems: Ataxia, balance issues, difficulty walking (cerebellar tumors)
• Hearing loss or ringing: Acoustic neuromas
• Hormonal symptoms: Pituitary tumors (menstrual changes, growth changes, etc.)

Diagnosis

Neurological Examination

• Mental status and cognitive function
• Cranial nerve examination (vision, eye movements, facial movement, hearing)
• Motor strength and coordination
• Sensory testing
• Reflexes and gait

Imaging Studies

• MRI brain with and without contrast (gold standard):
  • Best imaging modality for brain tumors
  • Provides detailed anatomic information
  • Can differentiate tumor types and grades to some extent
  • Gadolinium contrast enhancement indicates blood-brain barrier breakdown
  • Special sequences: FLAIR, diffusion-weighted imaging (DWI), perfusion, spectroscopy
• CT scan of brain:
  • Faster than MRI, useful in emergency settings
  • Less detailed than MRI
  • Good for detecting bleeding, bone involvement, calcifications
  • Used when MRI contraindicated (pacemaker, some metal implants)
• PET scan:
  • Not routine for initial diagnosis
  • Can help differentiate tumor recurrence from radiation necrosis
  • May aid in identifying high-grade areas for biopsy

Tissue Diagnosis

Definitive diagnosis requires tissue sample (except for some characteristic lesions):

• Stereotactic needle biopsy:
  • Minimally invasive procedure using image guidance
  • Small hole drilled in skull, needle inserted to obtain tissue
  • Used for deep tumors or patients not candidates for major surgery
  • Risks: bleeding (1-3%), infection (<1%), insufficient tissue for diagnosis (5-10%)
• Open surgical resection:
  • Craniotomy (opening skull) to remove tumor
  • Provides large tissue sample for comprehensive pathology
  • Therapeutic (removes tumor) and diagnostic

Pathology and Molecular Testing

Modern brain tumor classification integrates histology and molecular markers:

• WHO grading (1-4): Based on tumor features (mitoses, necrosis, vascular proliferation)
• Molecular markers (critical for diagnosis and prognosis):
  • IDH mutation status: IDH1 or IDH2 mutation indicates better prognosis
  • 1p/19q codeletion: Defines oligodendroglioma, predicts chemosensitivity
  • MGMT promoter methylation: Predicts benefit from temozolomide chemotherapy in glioblastoma
  • BRAF mutations: Targetable in some pediatric low-grade gliomas
  • EGFR amplification, TERT promoter mutations, ATRX loss: Additional prognostic/diagnostic markers

Additional Tests

• Visual field testing: For tumors near visual pathways
• Audiometry: Acoustic neuromas
• Hormone levels: Pituitary tumors
• Lumbar puncture (spinal tap): Primary CNS lymphoma, leptomeningeal disease (not done if increased intracranial pressure)
• Workup for primary cancer: If metastatic brain tumor suspected (CT chest/abdomen/pelvis)

Treatment

Surgery

Cornerstone of treatment for most brain tumors:

Craniotomy with Tumor Resection

• Goals:
  • Obtain tissue for diagnosis
  • Remove as much tumor as safely possible (maximal safe resection)
  • Relieve mass effect and symptoms
• Extent of resection impacts outcomes:
  • Gross total resection (GTR): Removal of all visible tumor - best outcomes
  • Subtotal resection (STR): Removal of most tumor
  • Biopsy only: Unresectable location or patient condition
• Advanced surgical techniques:
  • Awake craniotomy: Patient awake during surgery to map speech/motor areas, allows more aggressive resection while preserving function
  • Intraoperative MRI: Real-time imaging during surgery to maximize resection
  • Fluorescence-guided surgery (5-ALA): Tumor glows under special light, helps identify tumor margins
  • Neuronavigation: GPS-like system for precise tumor localization

Surgical Risks

• Neurological deficits (weakness, speech problems, vision changes): 5-15%
• Seizures: 10-20%
• Infection: 1-3%
• Bleeding: 1-2%
• CSF leak: 1-2%
• Risk varies by tumor location (eloquent areas like motor/speech cortex are higher risk)

Radiation Therapy

External Beam Radiation (EBRT)

• Standard fractionation: 1.8-2 Gy per day, 5 days/week, for 6 weeks (total 54-60 Gy)
• Indications:
  • Adjuvant therapy after surgery for high-grade gliomas
  • Primary treatment for unresectable tumors
  • Recurrent tumors
• Intensity-modulated radiation therapy (IMRT): Conforms dose to tumor shape, spares normal brain
• Proton beam therapy: Reduced dose to normal tissue, especially beneficial for pediatric tumors

Stereotactic Radiosurgery (SRS)

• High-dose focused radiation delivered in single session or few fractions
• Systems: Gamma Knife, CyberKnife, LINAC-based SRS
• Indications:
  • Metastatic brain tumors (1-4 lesions typically)
  • Small benign tumors (acoustic neuromas, small meningiomas)
  • Residual or recurrent tumors after surgery
• Advantages: Non-invasive, outpatient, single treatment
• Size limit: Usually <3-4 cm

Whole Brain Radiation Therapy (WBRT)

• Radiation to entire brain
• Indications:
  • Multiple brain metastases (>4-10 lesions)
  • Leptomeningeal disease
  • Some primary tumors (medulloblastoma, primary CNS lymphoma)
• Side effects: Cognitive decline, memory problems, fatigue (especially long-term)
• Hippocampal-sparing WBRT reduces cognitive side effects

Chemotherapy

Temozolomide (Temodar)

• Oral alkylating agent, standard for high-grade gliomas
• Concurrent with radiation: 75 mg/m² daily during radiation (6 weeks)
• Adjuvant (maintenance): 150-200 mg/m² days 1-5 of every 28 days for 6-12 cycles
• Well-tolerated, main side effect: myelosuppression (low blood counts)
• Most effective in MGMT-methylated glioblastomas
• Standard Stupp protocol (surgery + radiation + temozolomide) improved median survival from 12 to 15 months in glioblastoma

Other Chemotherapy Agents

• PCV (procarbazine, lomustine, vincristine): Oligodendrogliomas, anaplastic gliomas
• Bevacizumab (Avastin): VEGF inhibitor for recurrent glioblastoma
• High-dose methotrexate: Primary CNS lymphoma
• Lomustine (CCNU): Recurrent gliomas

Targeted Therapy and Immunotherapy

• BRAF inhibitors: Dabrafenib/trametinib for BRAF V600E mutant gliomas (rare in adults)
• MEK inhibitors: For NF1-associated and BRAF-fusion gliomas
• Immunotherapy:
  • Generally disappointing in glioblastoma (brain is immunoprivileged)
  • CAR-T therapy, vaccine trials ongoing
  • Checkpoint inhibitors for MSI-high tumors or TMB-high tumors (rare)

Tumor Treating Fields (TTFields, Optune)

• Low-intensity alternating electric fields delivered via scalp electrodes
• Approved for newly diagnosed and recurrent glioblastoma
• Added to temozolomide: improved median survival from 16 to 21 months in newly diagnosed GBM
• Worn 18+ hours/day
• Main side effect: scalp skin irritation
• Requires shaving head, compliance challenging

Supportive Care

• Corticosteroids (dexamethasone):
  • Reduce cerebral edema and mass effect
  • Rapid symptomatic improvement (hours to days)
  • Used perioperatively, during radiation, for symptom management
  • Tapered as soon as possible due to side effects
• Antiepileptic drugs (AEDs):
  • Levetiracetam (Keppra) most commonly used (fewer drug interactions)
  • Given to patients with seizures
  • Prophylactic AEDs (no seizures yet) generally NOT recommended
• Anticoagulation: Brain tumor patients have increased VTE risk; prophylaxis considered perioperatively

Prognosis and Survival

Survival by Tumor Type

Prognostic Factors for Glioblastoma

• Age: Most important clinical factor (younger = better)
• Performance status: Ability to perform daily activities
• Extent of resection: Gross total resection improves survival
• MGMT methylation: Median survival 21-24 months (methylated) vs 12-15 months (unmethylated)
• IDH mutation: Rare in primary GBM, but indicates better prognosis
• Tumor location: Resectability and eloquence

Living with a Brain Tumor

Neurological Rehabilitation

• Physical therapy: For weakness, balance, coordination problems
• Occupational therapy: Relearn daily activities, adaptive equipment
• Speech therapy: For aphasia, swallowing difficulties
• Cognitive rehabilitation: Memory, attention, executive function

Managing Side Effects

• Seizures: Take AEDs consistently, avoid triggers (alcohol, sleep deprivation)
• Cognitive changes: Memory aids, routines, cognitive rehabilitation
• Fatigue: Energy conservation, balance activity and rest
• Steroid side effects: Weight gain, insomnia, mood changes, elevated blood sugar, muscle weakness

Driving and Safety

• Driving restrictions vary by state
• Generally cannot drive: during active seizures, for period after last seizure (6-12 months typically)
• Check with neurologist and local DMV regulations
• Use caution with activities where loss of consciousness would be dangerous

Emotional and Psychological Support

• Depression and anxiety common (40-50% of patients)
• Counseling, support groups, psychiatric medication when needed
• Caregiver support essential - caregiving burden is high
• Advanced care planning and end-of-life discussions important

Frequently Asked Questions

What causes brain tumors?

For most brain tumors, the cause is unknown. The only proven environmental risk factor is ionizing radiation (especially in childhood). Rare inherited genetic syndromes account for <5% of cases. Despite extensive research, cell phones, power lines, diet, and most other suspected environmental factors have not been shown to cause brain tumors.

Are all brain tumors cancerous?

No. Many brain tumors are benign (non-cancerous), including most meningiomas, pituitary adenomas, acoustic neuromas, and craniopharyngiomas. However, even benign tumors can cause serious problems due to their location in the confined space of the skull and may require treatment. Benign tumors generally don't spread but can recur locally.

Can brain tumors be cured?

It depends on the type. Benign tumors (meningiomas, pituitary adenomas) can often be cured with surgery alone. Some malignant tumors in children (medulloblastoma) are curable in 70-80%. Unfortunately, adult high-grade gliomas (especially glioblastoma) are rarely cured with current treatments, though research is ongoing. Lower-grade gliomas can be controlled for many years but usually are not curable.

Why can't the entire tumor be removed?

Brain tumors, especially gliomas, often infiltrate normal brain tissue without clear borders. Removing all tumor cells would require removing functioning brain tissue, causing unacceptable neurological damage (paralysis, inability to speak, etc.). Surgeons aim for "maximal safe resection" - removing as much tumor as possible while preserving neurological function. Tumors in critical areas (speech, motor) are particularly challenging.

Will I lose my hair from brain tumor treatment?

It depends on treatment. Surgery: You'll have hair shaved in the surgical area, but it will grow back (though may be thinner). Radiation: Hair loss in the radiation field is common and may be permanent with high doses. Chemotherapy (temozolomide): Hair thinning is possible but complete hair loss is uncommon. Tumor Treating Fields (Optune): Requires shaving the entire head.

Can I work during treatment?

It varies by individual, tumor type, treatment, and job requirements. Many patients take disability during initial treatment (surgery and radiation) and may return to work afterward if neurologically able. Cognitive changes, fatigue, and seizure risk may limit some activities. Discuss capabilities and limitations with your healthcare team and employer.

What is the difference between a brain tumor and brain cancer?

"Brain tumor" is a general term for any abnormal growth in the brain, including benign tumors. "Brain cancer" specifically refers to malignant (cancerous) tumors that can grow rapidly and infiltrate normal brain tissue. Doctors use "brain tumor" as the broader, more accurate term since not all brain tumors are cancerous.

How quickly do brain tumors grow?

Growth rate varies dramatically by type. Glioblastomas grow rapidly (weeks to months to become symptomatic). Low-grade gliomas grow slowly (may be present for years before diagnosis). Meningiomas typically grow very slowly (millimeters per year). Growth rate affects symptoms, treatment urgency, and prognosis.

Should I get a second opinion?

Yes, absolutely. Brain tumors are complex, treatment is nuanced, and outcomes vary significantly. A second opinion from a neuro-oncologist or neurosurgeon at a comprehensive cancer center is recommended, especially for malignant tumors. Most insurance covers second opinions, and getting one will not delay treatment or offend your doctors.

Are there clinical trials available?

Yes, many clinical trials are available for brain tumors, especially glioblastoma. Trials test new chemotherapy agents, targeted therapies, immunotherapies, combinations, and novel approaches. Ask your neuro-oncologist about trials you may be eligible for, or search clinicaltrials.gov. Consider trials early - some are only available for newly diagnosed patients.

Sources and References

• National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines: Central Nervous System Cancers
• American Cancer Society: Brain and Spinal Cord Tumors in Adults
• National Cancer Institute SEER Database
• World Health Organization (WHO) Classification of Tumors of the Central Nervous System (2021)
• European Association of Neuro-Oncology (EANO) Guidelines
• Stupp R et al. Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. NEJM. 2005