Epidemiology

• Primary brain tumours represent about 1.6% of all tumours diagnosed in the UK.^[2] It has been estimated that the lifetime risk of developing brain and other central nervous system (CNS) cancer is 1 in 133 for men and 1 in 185 for women in the UK. The incidence of brain and CNS tumours in the UK in 2007 was 6.8 per 100,000 (male 8.1 per 100,000 and female 5.6 per 100,000).^[3]
• The incidence rates for brain and CNS cancers in the UK have increased slightly between 1975 and 2007. Some specific types of brain tumours are significantly increasing in incidence, eg gliomas in the elderly and lymphomas.^[3]
• There are more intracranial tumours reported in Africa, Japan and the Far East.^[4]
• The incidence of primary CNS lymphomas is 4-5 per 1,000 population among patients with AIDS and 0.3 per 100,000 in the immunocompetent population. The incidence of primary CNS lymphomas has increased in recent decades.^[5]
• In adults, most brain tumours are supratentorial and high-grade gliomas and meningiomas predominate.^[3] Brain tumours can develop at any age in adults but are most common in people aged between 50 and 70.^[3]

Risk factors

• Primary tumours of the brain are more common among more affluent groups but the reverse trend occurs for brain metastases.^[1]
• Ionising radiation.
• Vinyl chloride is associated with high-grade gliomas.
• Immunosuppression (eg as a result of AIDS) may cause cerebral lymphoma.
• Possible increased risk with oil refining, embalming, and textiles but these need further investigation.
• Mobile phone use: no definite link has been discovered between mobile phone use and brain tumours; however further data are needed.^[6][7]
• Inherited syndromes with an increased risk of brain tumours include neurofibromatosis, von Hippel-Lindau disease, tuberous sclerosis, Li-Fraumeni syndrome, Cowden's disease, Turcot's syndrome and naevoid basal cell carcinoma syndrome (Gorlin's syndrome).^[1]

Histological types of brain tumour

Metastases from other cancers are the most common intracranial tumours in adults, and are 10 times more common than primary tumours. The main histological types of brain tumours include:

• High-grade:
  • Gliomas (see separate article on Gliomas and Glioblastoma Multiforme).
  • Primary cerebral lymphomas.
  • Medulloblastomas.
• Low-grade:
  • Meningiomas (see separate Meningiomas article).
  • Acoustic neuromas.
  • Neurofibromas.
  • Pituitary tumours.
  • Pineal tumours.
  • Craniopharyngiomas.
• Secondaries:
  • Common malignancies spreading to the brain include lung cancer, breast cancer, stomach cancer, prostate cancer, thyroid cancer, colorectal cancer, melanoma and kidney cancer.

Presentation

Anyone presenting with new, unexplained headaches or neurological symptoms needs a thorough neurological history and examination. The presentation will depend on location and rate of growth but includes features of a space-occupying lesion and raised intracranial pressure (ICP) (see links for separate articles):

• Headache, which is typically worse in the mornings.
• Nausea and vomiting.
• Seizures.
• Progressive focal neurological deficits, eg diplopia associated with a cranial nerve defect, visual field defect, neurological deficits affecting the upper and/or lower limb.
• Cognitive or behavioural symptoms.
• Symptoms relating to location of mass, eg frontal lobe lesions associated with personality changes, disinhibition and parietal lobe lesions might be associated with dysarthria.
• Papilloedema (absence of papilloedema does not exclude a brain tumour).

Differential diagnosis

• Other causes of a space-occupying lesion (see link for separate article).
• Cerebrovascular event.
• Idiopathic intracranial hypertension.

Investigations

• Blood tests may be useful in determining any complications of the tumour, eg bleeding disorders, hypercalcaemia or inappropriate antidiuretic hormone secretion, or in the initial assessment of other possible causes of headache, eg ESR and CRP as indicators of possible giant cell arteritis.^[8]
• Diagnosis largely rests on brain imaging, eg CT scan and/or MRI scan (both with or without contrast). MRI is more sensitive. The spine may also need to be imaged, especially in CNS tumours that spread to the spine, eg germ cell tumours and lymphoma.^[9]
• Technetium brain scan: is useful in diagnosis of destructive skull vault (eg metastases) and skull base lesions.
• Imaging using labelled amino acid analogues may be indicated for detection of viable tumour tissue, tumour delineation, selecting the best biopsy site and planning therapy.^[10]
• Magnetic resonance angiography (MRA) and magnetic resonance spectroscopy (MRS) are occasionally used to define changing size or blood supply. Positron emission tomography (PET) is helpful in grading gliomas or locating an occult primary.
• Biopsy and tumour removal: stereotactic biopsy via a skull burr-hole to obtain histology of a suspected malignancy. Open exploration (craniotomy) may be required, eg for a symptomatic meningioma.

Indications for referral^[11]

Refer urgently (to be seen by a specialist within 2 weeks) patients with:

• Symptoms related to the CNS, including:
  • Progressive neurological deficit, eg cranial nerve palsy, unilateral sensorineural deafness.
  • New-onset seizures.
  • Headaches of recent onset accompanied by features suggestive of raised intracranial pressure (ICP), including:
    • Vomiting, drowsiness, posture-related headache, pulse-synchronous tinnitus.
    • Other focal or non-focal neurological symptoms (eg blackout), change in personality or memory.
    • A new, qualitatively different, unexplained headache that becomes progressively severe.
  • Mental changes.
• Rapid progression of:
  • Subacute focal neurological deficit.
  • Unexplained cognitive impairment, behavioural disturbance or slowness, or a combination of these.
  • Personality changes confirmed by a witness and for which there is no reasonable explanation even in the absence of the other symptoms and signs of a brain tumour.

Refer urgently patients previously diagnosed with any cancer who develop any of the following symptoms:

• Recent-onset seizure.
• Progressive neurological deficit.
• Persistent headaches.
• New mental or cognitive changes.
• New neurological signs.

Consider non-urgent referral or discussion with a specialist for unexplained headaches of recent onset:

• Present for at least 1 month.
• Not accompanied by features suggestive of raised ICP.

Staging

There is no standard staging system for brain tumours. Brain tumours can spread to other parts of the brain and the spinal cord - but distant metastases are rare.

Management

See also the separate article on Rising Intracranial Pressure.

Surgery

• Tumours should be resected whenever possible. Surgery will also provide tissue for a formal diagnosis.
• Surgery may not be a viable option, especially if the tumour is located in a region associated with critical function or where there is infiltration of local normal brain tissue.
• Surgery should also be considered to reduce mass effect and treat hydrocephalus in order to provide symptomatic relief.
• If surgery is not an option then radiotherapy should be considered.

Photodynamic therapy can be carried out at the same time as surgical resection. A photosensitising agent is injected (usually intravenously, sometimes by direct injection into the tumour). The photosensitising agent is activated by illuminating the selected area with a laser source. Because of limited evidence of efficacy and safety, this procedure is not currently recommended by the National Institute for Health and Clinical Excellence (NICE) for routine patient care.^[12]

Radiation

• External beam radiotherapy can be curative for many patients and also prolongs survival.
• For some types of tumours, it is the treatment of choice, eg metastatic brain tumours, leptomeningeal metastases.
• Whole brain radiation is used with some tumours, eg medulloblastomas, primary CNS lymphomas. An alternative technique is 'involved-field radiation', which means that normal brain tissue is exposed to less radiation.^[9]
• In stereotactic radiosurgery, focal radiotherapy is administered to a target, thus avoiding exposure to normal brain tissue.

Chemotherapy

• The role of chemotherapy in brain tumours is not as marked as in other tumours (except for CNS lymphoma, which requires aggressive intrathecal and intravenous chemotherapy).
• It does provide modest benefit and is important in palliative care and as an adjunct to combined surgery and radiotherapy.
• Commonly used agents include those that can cross the blood brain barrier, eg temozolomide in gliomas, nitrosureas in oligodendrogliomas, platinum agents in medulloblastomas.^[9][13]

Other therapeutic agents

• Patients may also require analgesics, anticonvulsants, anticoagulants and corticosteroids.
• Corticosteroids help to reduce mass effect and intracranial pressure (ICP).

Treatment of brain metastases^[14]

• Corticosteroids should be used if cerebral oedema is present.
• Surgery may be an option for patients with 3 or fewer brain metastases - provided the primary is controlled. This is associated with improved survival.
• For metastases that are 3-3.5 cm in size, stereotactic radiosurgery may be an option.
• Whole-brain radiotherapy can be given after surgery or radiosurgery. However, it is currently debated whether it should be given early or late in the illness.
• Whole-brain radiotherapy is the only treatment modality for those who are not suitable for surgery or radiosurgery.
• Chemotherapy should be considered if the brain secondaries arise from a primary chemosensitive tumour.

Palliative care

See separate articles on Palliative Care, Pain Control in Terminal Care, Nausea and Vomiting in Palliative Care, Prescribing in Palliative and Terminal Care, Terminal Care, Looking After People With Cancer and Helping Patients Face Death and Dying.

Complications^[8]

• Acute haemorrhage into a tumour.
• Blockage of cerebrospinal fluid outflow, causing hydrocephalus. Sudden death may occur as a result of obstruction of outflow drainage from the third ventricle.
• Sudden increases in intracranial pressure (ICP) may lead to life-threatening brain herniation through the foramen magnum or transtentorial foramina.
• Complications of radiotherapy: acute toxicity is rare with modern schedules but subacute or chronic effects may occur:
  • Subacute encephalopathy with somnolence and headaches may occur 6-16 weeks after radiation therapy.
  • Prolonged radiation treatment may lead to impairment of intellectual capacity.

Prognosis

• Brain tumours, both benign and malignant, are associated with morbidity relating to mass effect if they continue to increase in size.^[15]
• Malignant brain tumours are the leading cause of death from solid tumours in children and the third most common cause in adolescents and young adults (up to the age of 34).