Clinical review: Glioma

Contributed by Mr Keyoumars Ashkan, consultant neurosurgeon and senior lecturer, King's College Hospital, London.

T1 MRI showing tumour

Section 1: Epidemiology and aetiology
With an incident rate of 7.7 per 100,000 population, primary brain tumours represent two per cent of all tumours. In children, they are the commonest of all solid tumours.

In adults, the incidence steadily increases with age, reaching a peak in the seventh decade of life. As a single group, gliomas account for about 50 per cent of all primary brain tumours.

Gliomas are tumours arising from glial cells, which are the supporting cells of the central nervous system. Depending on the glial cell of origin, gliomas are classified as astrocytomas (the commonest), oligodendrogliomas, ependymomas or mixed glial tumours.

Grades of glioma
Gliomas are graded as 1 to 4, according to behaviour and in particular the rate of growth and thus prognosis. Grade 1 tumours are essentially benign and a disease of childhood, whilst grade 4 tumours, also known as glioblastomas, are the most aggressive.

Both grade 3 and 4 tumours are termed as high grade gliomas and considered malignant. Grade 2 tumours are slow growing and not malignant, but do have a tendency to progress over a variable time period into higher grade gliomas.

High grade gliomas arising from lower grade gliomas are labelled as secondary and occur in younger patients. Primary high grade gliomas arise de novo and occur in older patients.

The aetiology of gliomas remains uncertain. The incidence is somewhat higher in males than females and this has raised the possibility of potential links to agricultural and industrial chemicals. Radiation exposure is a definite risk.

There is no evidence that the use of mobile phones increases the risk of developing brain tumours, although caution has been advised against prolonged use in children given their developing nervous system.

Genetic factors are also relevant and probably account for around five per cent of all cases. In terms of distribution, frontal lobes are the commonest sites for adult gliomas.

Section 2: Making the diagnosis
Patients with gliomas usually present in one of three ways: with symptoms of raised intracranial pressure, with focal neurological deficits or with seizures. Raised intracranial pressure may manifest as headaches, usually early in the morning or on waking, blurred vision, nausea or vomiting.

Progressive raised pressure may result in confusion and depressed level of consciousness.

If the tumour is located in close proximity to the cerebral ventricular system, especially in the cerebellum, then hydrocephalus may be the presenting feature.

Focal neurological deficits
The focal neurological deficits caused by gliomas are directly related to their location. Therefore, a location in the frontal lobes near the motor cortex may lead to contralateral hemiparesis, whilst a tumour in the visual pathway may present with visual failure.

Sixth nerve palsy is often termed a false localising sign as most commonly it is the result of generalised raised intracranial pressure rather than a true focal sign. Most forms of epilepsy have been described in patients with gliomas.

An adult patient with a first focal seizure particularly warrants urgent investigation.

T1 weighted MRI (left) and FLAIR MRI (right). FLAIR MRI demonstrates the tumour not evident using T1 (arrowed)

In terms of investigations, imaging techniques are by far the most useful.1 By and large CT has been superseded by MRI. MRI provides detailed information about the location, structure and relationship of gliomas to adjacent structures in all three planes.

The degree of surrounding oedema and flattening of the cortical sulci and gyri are also demonstrated, which are indications of the overall mass effect produced by the tumour. Newer fluid-attenuated inversion recovery (FLAIR) MRI sequence is particularly useful in detecting more subtle gliomas which might otherwise be missed.

Different types of gliomas have differing MRI characteristics. As a general rule, contrast enhancement on CT or MRI by a glioma implies breakdown of the blood-brain barrier and is an indicator of high grade activity.

Furthermore, low grade gliomas tend to have a more homogenous uniform appearance on MRI compared with high grade tumours, which often appear heterogeneous with solid and cystic components.

However, there are exceptions to this rule, a notable one being pilocytic astrocytomas, most commonly seen in children, which are usually cystic with solid enhancing components despite being histologically a grade 1 tumour.

Imaging may also be useful for predicting the subtype of gliomas. Oligodendrogliomas tend to have areas of calcification within the tumour, whilst ependymomas most commonly occur in close proximity to the cerebrospinal fluid pathways and the lower spine.

Newer MRI techniques, such as functional MRI and tractography (imaging of the neural tracts), allow detailed assessment of the relationship between the glioma and the adjoining eloquent cortex and white matter tracks, such as the motor and speech cortices or the internal capsule and optic radiation.

Differential diagnoses
Differential diagnoses of gliomas include other brain tumours and brain metastasis.

Investigations including CT scans of chest, abdomen and pelvis as well as measurement of serum tumour markers will be useful to rule out any primary tumours in the body.

A brain abscess is difficult to differentiate from a cystic glioma.

Fever and raised inflammatory markers have poor predictive value unless there is overt clinical evidence of sepsis.

Diffusion weighted MRI may be useful as it will show free diffusion in the fluid centre of a cystic tumour versus restricted diffusion in an abscess containing thick pus.2

Nonetheless if there is a diagnostic dilemma, given the critical nature of patients with brain abscess and the risk of sudden deterioration, an urgent neurosurgical opinion is indicated.

Despite advances in neuro-imaging, tissue diagnosis remains the gold standard for diagnosis of gliomas.

Section 3: Managing the condition
Patients with brain tumours are now managed by a multidisciplinary team (MDT), comprising specialists, clinical nurse specialists and allied health professionals.

The team meets at least weekly to discuss each patient prospectively and decide on the best course of treatment.

Multiple factors influence the best form of treatment, in particular the general fitness level of the patient, the neurological status and mode of presentation, the size and location of the tumour and the radiological appearance, especially whether the tumour is likely to be a high or low grade glioma.

In patients with radiological suspicion of a high grade glioma, unless there is a contraindication to surgery because of poor general medical or neurological status, then neurosurgery is indicated.

A short course of high-dose steroids will achieve both symptomatic improvement and help the conduct of the surgery by reducing the surrounding oedema.

The primary role of surgery is to establish tissue diagnosis. In patients with symptoms of raised intracranial pressure, debulking surgery is also important for symptomatic control.

Given that by the time of presentation, high grade glioma cells will have spread well beyond the visible margins of the tumour, opinion is divided about whether extent of surgical resection confers prognostic benefit.

Nonetheless where safe and possible, most advocate radical surgery to reduce tumour burden ahead of any adjuvant therapy. Furthermore, recent NICE appraisal on effectiveness of intra operative carmustine chemotherapy in patients in whom at least 90 per cent of the tumour is removed has fuelled interest in radical surgery for high grade gliomas.

A new and useful technique to promote radical resection is fluorescent guidance in which patients ingest 5-aminolevulinic acid prior to surgery.3 This is taken up by the high grade glioma cells, causing them to fluoresce pink when viewed under blue light compared with the normal brain which appears blue, thus increasing the visibility of the tumour for resection.

Fluorescent guided tumour resection: residual tumour seen in pink (below)

Post operative radiotherapy has been shown conclusively to confer prognostic benefit in patients with high grade gliomas.4

Most patients undergo a six-week course of treatment, although shorter courses may be used in patients who are less fit. Concomitant chemotherapy with temozolomide alongside radiotherapy is indicated in patients with grade 4 tumours and good medical and neurological status.

Post-radiotherapy chemotherapy with temozolomide or PCV (procarbazine, lomustine and vincristine) may also be used, particularly in patients with radiological evidence of disease progression.

Managing low grade gliomas
Until recently, many patients with radiological features of low grade gliomas were managed conservatively with watchful waiting and MRI surveillance.

The rationale was to reserve any intervention until the tumour showed evidence of progression to a high grade glioma.

Improved understanding of the natural history of low grade, particularly grade 2, gliomas with almost inevitable progression to high grade gliomas, and the evidence in favour of prognostic benefit and potential cure with total resection, have significantly changed the management of patients with low grade gliomas.5

Where possible, total excision is recommended by most MDTs. Techniques such as awake surgery with motor and language mapping are useful to increase the safety and extent of surgery in low grade gliomas in and near eloquent brain.

Whether subtotal resection confers any prognostic advantage remains unclear. The timing of adjuvant therapy for low grade gliomas also remains controversial with most MDTs reserving this until the tumour progresses to a high grade glioma.

In patients with large tumours, especially over 6cm, adjuvant therapy may be considered earlier, especially if there is evidence of mass effect and surgery cannot be contemplated on technical grounds.

Section 4: Prognosis
The most important factor determining the prognosis of patients with gliomas is the grade of the tumour.

Although the outcome of patients with high grade gliomas remains poor, advances in surgical techniques, adjuvant treatment and molecular neuropathology in the last decade, have resulted in better outcomes.

Survival of two years or more is now seen in cohorts of patients with glioblastoma who present with good performance and neurological status, have favourable genetic mutations, such as IDH 1 mutation and methylated MGMT promoter, and undergo radical surgery with intra operative chemotherapy followed by concomitant post operative radiotherapy and chemotherapy.

In patients with poor performance status, palliative care services provide a central management role.

Grade 2 gliomas
In patients with grade 2 gliomas, favourable median survival of seven years or more is associated with younger age, tumour size of less than 6cm and preserved neurological function.6

Progression to a higher grade tumour is usually the main factor confounding the prognosis of patients with grade 2 gliomas. As discussed above, total resection of such tumours, if technically possible, may achieve cure but will need to be done before progression occurs.

Grade 1 gliomas are benign with little or no chance of recurrence or progression after successful resection.

The GP's role is crucial not only in managing the physical consequences of the disease but also providing support for the patient and their relatives.

Section 5: Case study
A 55-year-old man first presented to his GP with a four-week history of progressively worsening headaches. The headaches were interrupting his sleep and although he had not vomited, he had been feeling nauseous.

His wife said that he had been walking into things and they had planned to visit an optician to have his eyes checked. His family and past medical histories were unremarkable.

On examination the GP detected bilateral papilloedema raising the suspicion of an intracranial mass lesion. The patient was referred to the local neurologist under the two-week suspected cancer pathway.

Evaluation by the neurologist further demonstrated a left visual field defect precipitating an urgent MRI scan.

High grade tumour
Given the MRI features of a high grade tumour, the patient was referred by the neurologist to the local neurosurgical unit for discussion in the neuro-oncology MDT. In the meantime the patient was started on dexamethasone 8mg twice daily. The MDT recommended surgery to debulk the tumour the following week.

This was performed without any complications. Although over 90 per cent of the tumour was removed, no intra operative carmustine chemotherapy was administered because of the close proximity of the tumour to the occipital horn of the right lateral ventricle and risk of leakage of the chemotherapy drug into the cerebrospinal fluid pathway.

The patient's headaches and papilloedema resolved after surgery but the visual field defect persisted. The histology was found to be consistent with a glioblastoma. Given the patient's good performance status, the MDT recommended concomitant radiotherapy and temozolomide chemotherapy.

Management plan
The surgeon and clinical nurse specialist subsequently met with the patient and his family to discuss the diagnosis and the management plan. It was explained that although the adjuvant treatment would not achieve a cure, it had a good chance of extending life expectancy.

The patient was clearly upset by his diagnosis but did mention that he had been suspecting it for some time.

In the course of the following weeks, the patient started his adjuvant therapy and indeed managed to complete this as planned.

Fatigue was the main adverse effect he experienced during the treatment. At one year follow up, there was no evidence of disease progression and he remained clinically stable. He was kept under follow up with three-monthly MRI scans.

Section 6: Evidence base
Clinical trials

  • European Organisation for Research and Treatment of Cancer 22845 randomised trial.

A European study of 314 patients with low grade gliomas randomised to receive either early radiotherapy after surgery or deferred radiotherapy until the time of progression. The main findings were that early radiotherapy did not increase the overall survival but did improve the seizure control. Lancet 2005; 366: 985-90

  • NCOG 6G61 randomised phase III trial.

A North American trial of post-radiation chemotherapy in 148 patients with high grade gliomas with either carmustine alone or combination therapy with PCV. The latter was found to be associated with significantly longer survivals. Int J Radiat Oncol Biol Phys 1990; 18(2): 321-4 and J Neurosurg 1985; 63(2): 2: 18-23


  • NICE Technology Appraisal. Carmustine implants and temozolomide for the treatment of newly diagnosed high grade glioma. London, NICE, 2007.
  • NICE. Improving outcomes for people with brain and other central nervous system tumours. London, NICE, 2006.
  • NICE Technology Appraisal. Temozolomide for the treatment of recurrent malignant glioma. London, NICE, 2001.

Key texts

  • McGirt M, Chaichana K, Gathinji M, et al. Independent association of extent of resection with survival in patients with malignant brain astrocytoma. J Neurosurg 2009; 110(1): 156-62
  • McGirt M, Chaichana K, Attenello F, et al. Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery 2008; 63(4): 700-7
  • Westphal M, Hilt D, Bortey E, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol 2003; 5(2): 79-88
  • Stupp R, Dietrich P, Ostermann Kraljevic S, et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 2002; 20(5): 1375-82


The RCGP covers this topic in statement 12 of the RCGP curriculum, Care of People with Cancer and Palliative Care. 


Reflect on this article and add notes to your CPD Organiser on MIMS Learning


These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Perform a search of patients who have been diagnosed with a brain tumour.
  • Determine the proportion of patients who presented with classic symptoms of raised intracranial pressure.
  • Review the notes of patients who have died from a glioma to determine whether their end-of-life care was optimal and if any improvements could have been made.
  • Consider having a practice meeting with a local neurosurgeon to discuss the diagnosis and current management of gliomas.

1. Cha S. Neuroimaging in neuro-oncology. Neurotherapeutics 2009; 6(3): 465-77.

2. Kastrup O, Wanke I, Maschke M. Neuroimaging of infections of the central nervous system. Semin Neurol 2008; 28(4): 511-22.

3, Stummer W, Pichlmeier U, Meinel T et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 2006; 7(5): 392-401.

4, Walker M, Alexander E, Hunt W et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. J Neurosurg 1978; 49 (3): 333-43.

5, McGirt M, Chaichana K, Attenello F et al. Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery 2008; 63(4): 700-7.

6, Pignatti F, van den Bent M, Curran D et al. Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 2002; 20(8): 2076-84.

  • Visit our GP Curriculum Centre for hundreds of articles linked to key topics in the RCGP curriculum.

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