Brain tumour: symptoms, treatment and survival

A brain tumour is an abnormal mass of cells in or around the brain. Brain tumours may be primary (arising from brain tissue, including glial cells, meninges or other structures) or secondary (metastases from cancers elsewhere in the body — lung, breast, melanoma and renal cancers are the most common primary sources of brain metastases). Primary brain tumours are classified WHO Grade I–IV, with higher grades being more malignant and faster-growing. Not all brain tumours are cancerous — meningiomas, which account for approximately one-third of all primary brain tumours, are usually benign.

Symptoms depend on the tumour's location and rate of growth. Common symptoms include: persistent or progressive headaches — particularly ones that are worse in the morning or that wake the patient from sleep; new-onset seizures (fits) — one of the most specific warning signs for a brain lesion; weakness or numbness on one side of the body (hemiparesis/hemisensory loss); speech or language difficulties (dysphasia); personality or behaviour changes; cognitive impairment or memory loss; visual disturbances; nausea and vomiting (caused by raised intracranial pressure); and coordination or balance problems. Any new neurological symptom should be investigated.

Glioblastoma (GBM) — WHO Grade IV glioma — is the most common and most aggressive primary malignant brain tumour. It accounts for approximately 50% of all primary malignant brain tumours in the UK. GBM grows rapidly, infiltrates surrounding brain tissue (making complete surgical removal impossible) and invariably recurs. Despite maximal safe resection, concurrent chemoradiotherapy (Stupp protocol) and adjuvant temozolomide, median survival is approximately 15 months. Approximately 5% of patients survive five years. MGMT promoter methylation predicts better response to temozolomide.

A meningioma is a tumour arising from the meninges — the membranous coverings of the brain and spinal cord. It is the most common primary brain tumour type overall and is usually benign (WHO Grade I). Most meningiomas grow slowly and may be monitored with serial MRI if small and asymptomatic ('watch and wait'). Larger, symptomatic or growing meningiomas are treated with surgical resection, which may be curative for accessible Grade I tumours. Atypical (Grade II) and anaplastic (Grade III) meningiomas have a higher recurrence risk and may require adjuvant radiotherapy.

Headaches are extremely common and are caused by a brain tumour in only a very small proportion of cases. However, certain features make headaches more concerning: progressive worsening over weeks; waking from sleep; worst in the morning and improving during the day (suggesting raised intracranial pressure); associated with nausea, vomiting or neurological symptoms; new headache in someone over 50 without a prior history of headaches; or headache occurring alongside cognitive change, personality change or seizures. Isolated headaches without neurological features are rarely caused by brain tumours.

Yes — a new-onset seizure in an adult is one of the most important warning signs for a brain tumour and always requires urgent assessment and brain MRI. Seizures are caused by abnormal electrical activity triggered by the tumour irritating the cerebral cortex. The type of seizure depends on the tumour's location: focal motor seizures (twitching or jerking of a limb), focal sensory seizures (tingling or numbness), focal cognitive seizures (déjà vu, strange sensations) or generalised tonic-clonic seizures (convulsions). Approximately 50–60% of patients with low-grade gliomas and 30–40% with GBM present with seizures.

MRI of the brain with gadolinium contrast is the gold-standard investigation for suspected brain tumours, providing detailed imaging of tumour location, extent and relation to critical brain structures. CT is used in emergencies. The definitive diagnosis requires histopathological examination of tumour tissue — obtained either by surgical resection or stereotactic biopsy (a minimally invasive procedure using imaging guidance to take a small tissue sample). Modern brain tumour diagnosis integrates histology with molecular markers including IDH mutation, 1p/19q codeletion and MGMT promoter methylation.

Treatment depends on the tumour type, grade and location. Benign tumours (meningioma, acoustic neuroma): watchful waiting for small asymptomatic tumours; surgery for large or symptomatic tumours; stereotactic radiosurgery (Gamma Knife, CyberKnife) for suitable lesions. Malignant primary tumours (GBM, high-grade glioma): maximal safe surgical resection followed by the Stupp protocol — concurrent temozolomide chemotherapy and radiotherapy (60 Gy/30 fractions), then adjuvant temozolomide. MGMT-methylated GBM: lomustine + temozolomide. Recurrent GBM: bevacizumab, re-irradiation, or trial participation.

The Stupp protocol is the standard treatment regimen for newly diagnosed glioblastoma (GBM). Published by Roger Stupp in the New England Journal of Medicine in 2005, it consists of: concurrent temozolomide chemotherapy (75 mg/m² daily throughout) and external beam radiotherapy (60 Gy delivered in 30 fractions over 6 weeks), followed by six cycles of adjuvant temozolomide (150–200 mg/m² for 5 days every 28 days). Compared with radiotherapy alone, the Stupp protocol improved median survival from 12.1 to 14.6 months and five-year survival from 2% to 10%. It remains the global standard of care for GBM.

MGMT (O⁶-methylguanine-DNA methyltransferase) is a DNA repair enzyme that counteracts the effects of temozolomide chemotherapy. When the MGMT gene promoter is methylated (silenced), the enzyme is not produced — meaning the tumour cannot repair the DNA damage caused by temozolomide. MGMT promoter methylation is found in approximately 40–45% of GBMs and is a positive prognostic marker — patients with methylated MGMT survive longer and respond better to temozolomide. MGMT methylation status is now routinely tested and is used to guide treatment decisions, including the addition of lomustine in newly diagnosed methylated GBM.

Awake craniotomy is a neurosurgical technique in which the patient is kept conscious and responsive during part of the brain tumour resection operation, while the surgical area is under local anaesthesia. The awake phase allows the neurosurgeon to map eloquent cortex in real time — asking the patient to speak, move or carry out tasks whilst the surgeon stimulates adjacent brain areas. This technique maximises tumour removal whilst avoiding damage to critical areas controlling speech, language and motor function. It is used when tumours are located near eloquent cortex.

Stereotactic radiosurgery (SRS) — such as Gamma Knife, CyberKnife or Linac-based SRS — delivers a precisely focused, high dose of radiation to a brain lesion in a single or few sessions, sparing surrounding brain tissue. Despite the name, it does not involve any surgical incision. SRS is used for: brain metastases (1–3 lesions typically); benign tumours (acoustic neuromas, meningiomas); and recurrent or residual malignant tumours in select cases. It is not a treatment for GBM as a primary therapy due to the tumour's diffuse infiltrative nature.

Survival varies enormously by tumour type and grade. Meningioma (Grade I): five-year survival approximately 90%. Low-grade glioma (Grade II astrocytoma, IDH-mutated): median survival 5–10+ years. Anaplastic glioma (Grade III): median survival approximately 2–5 years depending on molecular profile. Glioblastoma (Grade IV): median survival approximately 15 months with Stupp protocol; five-year survival approximately 5%. IDH-mutated GBM has a significantly better prognosis than IDH-wildtype GBM. Overall five-year survival for all primary brain and CNS tumours combined in England is approximately 40%.

The vast majority of brain tumours are sporadic. A small proportion are associated with hereditary conditions: neurofibromatosis type 1 (NF1) — associated with optic gliomas and other gliomas; neurofibromatosis type 2 (NF2) — associated with bilateral acoustic neuromas (schwannomas), meningiomas and ependymomas; Li-Fraumeni syndrome (TP53 mutation) — associated with GBM and other brain tumours; Von Hippel-Lindau disease — associated with haemangioblastomas; and Gorlin syndrome (PTCH1 mutation) — associated with medulloblastoma. Genetic counselling and testing are offered to families with suspected hereditary brain tumour syndromes.

Brain tumours — particularly those in the frontal lobes, which control personality, behaviour, executive function, decision-making and emotional regulation — can cause marked personality and behaviour changes. These may include: increased irritability or aggression; emotional blunting or apathy; disinhibition (inappropriate behaviour or remarks); impulsivity; reduced empathy; difficulty concentrating; and social withdrawal. Personality change caused by a brain tumour can precede other neurological symptoms by months and may initially be attributed to stress, depression or other psychiatric conditions.

The incidence of primary brain tumours in the UK has risen slightly over the past three decades. This increase is real (not merely a detection artefact) and is most pronounced for glioblastoma. The cause of this increase is unknown — it does not appear to be related to mobile phone use, as large prospective studies (including the Million Women Study and INTERPHONE) have not found a causal link. Brain tumour incidence is highest in older age groups (peak 65–79 years for GBM) and is slightly higher in men than women for glioma.

Key UK support organisations include: The Brain Tumour Charity (information, support groups, research funding); Brain Tumour Research (research charity); Brainstrust (personalised support for patients and families); Macmillan Cancer Support (practical, financial and emotional support); and NHS neurological rehabilitation services. NHS specialist neuro-oncology multidisciplinary teams (MDTs) coordinate treatment, and clinical nurse specialists (CNSs) are a key point of contact. NICE guidelines mandate access to a key worker for all brain tumour patients.

Neurosurgical capacity for brain tumour resection is severely limited in most low-income countries — neurosurgeons may be absent or concentrated in one or two cities, and the intraoperative technology (iMRI, 5-ALA, awake craniotomy equipment) used routinely in UK centres is unavailable. Temozolomide and other chemotherapy drugs, radiotherapy equipment and the specialist MDT infrastructure are largely absent or unaffordable to poor patients. World Aid Network funds cancer treatment through locally-licensed oncologists, supporting improved access to life-saving care.