Brain tumours (primary) and brain metastases in over 16s

Why the committee made the recommendations

The evidence indicated that standard structural MRI is useful in distinguishing high-grade from low-grade glioma. The committee noted that this knowledge will inform management. Based on their experience, the committee recommended a protocol that they defined as a minimum standard for imaging acquisition.

No evidence was found on more advanced MRI techniques. However, the committee agreed that in their experience such techniques can be useful for assessing malignant features of a tumour – in particular, for ensuring that high-grade tumours are not misdiagnosed as low-grade tumours, which could have serious consequences for people who receive suboptimal management as a result. However the committee explained that a specialist multidisciplinary team would be needed to interpret features of the scan and decide management, even if advanced techniques were used.

How the recommendations might affect practice

Currently, various imaging strategies are used in different centres and depending on the person's circumstances. These recommendations aim to reduce variation in practice, and ensure that images obtained at different sites and using different equipment can be more accurately compared. Some centres may need to change their imaging protocols. This might increase or reduce costs depending on the imaging protocols which are currently in place.

Full details of the evidence and the committee's discussion are in evidence review A: investigation, management and follow-up of glioma.

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Why the committee made the recommendations

Molecular markers are an emerging and important area in the treatment of brain tumours. The committee looked for evidence on these markers but did not find any. However, they noted that there are some molecular markers for which the evidence of benefit if tested is overwhelming, as reported in studies identified in searches for other review questions. This applies in particular for MGMT promoter methylation and TERT promoter mutations in IDH-wildtype glioma, although the committee agreed the evidence was of a higher quality in the first case than the second. The committee agreed that even these markers are not being consistently tested for and that testing should be standardised. Therefore they made recommendations based on their knowledge and experience, highlighting the World Health Organization (WHO) classification, to ensure that all centres follow a consistent process for assessing and interpreting information on molecular markers. This was important, since failure to consistently report molecular markers can mislead clinicians or limit treatment options.

How the recommendations might affect practice

As testing for molecular markers is relatively new, practice can vary widely and this is to be expected. In principle there should not be a major change, although the time taken to implement the new molecular tests will vary significantly between centres.

Full details of the evidence and the committee's discussion are in evidence review A: investigation, management and follow-up of glioma.

Return to recommendations

Why the committee made the recommendations

There was evidence that optimal resection of a large percentage of the tumour improved survival for people with low-grade glioma. The committee noted that it is sometimes not appropriate to offer maximal safe resection (for example, if the balance of risks and benefits favours not resecting all areas) and that a specialist surgical team should look at the value of doing an operation given its safe extent. They agreed that biopsy should be considered in these cases, based on limited evidence showing improved overall survival after biopsy compared with active monitoring. However, the committee also concluded that some tumours were of such limited risk that the risks of surgery outweighed the possible gain of biopsy or resection.

The committee described how there was no evidence for immediate intervention, but that intervention should not be delayed due to the probability that surgical resection would have benefit for the person with the tumour. They therefore recommended intervention within 6 months, to allow for time to discuss treatment options with the person with the tumour. This also allows for the possibility of a second imaging sequence to be done later to look for progression and to assess for symptom change, as the committee also recognised that a proportion of low-grade gliomas have unfavourable gene profiles (for example, IDH wildtype) that make them more like high-grade tumours from a prognostic perspective.

A small number of people might have had initial treatment before it was standard practice to save a tissue sample for biopsy, and these people would currently be actively monitored. Based on their experience the committee agreed that these people may not need further surgery as long as their condition is stable (that is, they are not showing radiological or clinical disease progression).

How the recommendations might affect practice

The recommendations are likely to change practice at some centres, and remove unnecessary variation. There are currently differences between centres in which molecular diagnoses are performed and in treatment of very low-risk, low-grade tumours. This is partly because low-grade gliomas may be managed by non-expert surgical teams.

The recommendation about the management of low-grade gliomas that have been managed but then progress is unlikely to substantially change practice, as management would be largely unchanged.

Full details of the evidence and the committee's discussion are in evidence review A: investigation, management and follow-up of glioma.

Return to recommendations

Why the committee made the recommendations

There was evidence that PCV chemotherapy (procarbazine, CCNU [lomustine] and vincristine) after radiotherapy improved overall survival and progression-free survival compared with radiotherapy alone. The committee discussed how the evidence for the exact regime was complex, and used their judgement to recommend possible sequence and dose. In addition, the committee noted that there are some circumstances where radiotherapy and PCV might not be appropriate (particularly for the very lowest-concern and highest-concern low-grade tumours) and made recommendations based on their experience in these cases.

The committee included approximate age cut‑offs based on evidence showing that treatment improved survival in people aged around 40 or over with or without residual tumour, and their clinical judgement that treatment would be unlikely to be of benefit for people aged around 40 or under without residual tumour.

The committee found no evidence on the treatment of IDH wildtype grade II glioma. They determined that management of this type of glioma was likely to be different from other low-grade glioma, as IDH wildtype grade II glioma behaves more like a high-grade glioma. The committee therefore made a research recommendation on whether treating this tumour type more like a grade II glioma or grade IV glioma was most beneficial.

How the recommendations might affect practice

These recommendations aim to standardise practice. They will probably result in the same amounts of chemotherapy and radiotherapy being given, but these treatments will be more precisely targeted and it is possible that they will be given earlier. This would result in more people requiring long-term treatment for the side effects of radiation and chemotherapy. More people are likely to have active monitoring alone, which is not likely to create a resource impact.

Full details of the evidence and the committee's discussion are in evidence review A: investigation, management and follow-up of glioma.

Return to recommendations

Why the committee made the recommendations

The committee considered evidence for grade III and grade IV glioma separately.

How the recommendations might affect practice

Adjuvant PCV for treating codeleted grade III glioma is standard practice, but adjuvant temozolomide for non-codeleted grade III gliomas is a change in practice. However, some centres may already have started to adopt this as standard care, since the results of the study supporting this treatment were made publicly available in 2016.

Full details of the evidence and the committee's discussion are in evidence review A: investigation, management and follow-up of glioma.

Return to recommendations

Why the committee made the recommendations

The committee considered evidence for grade III and grade IV glioma separately.

How the recommendations might affect practice

For younger people with a grade IV glioma and a good performance status, a course of radiotherapy with concurrent and adjuvant temozolomide is standard care. However, for people aged around 70 and over, particularly those with a glioma with methylated MGMT, the use of concurrent and adjuvant temozolomide with 15 fractions of radiotherapy is a change of practice that will probably result in more people being treated. This is a relatively small group of people, and so the recommendation is unlikely to have a significant resource impact.

Full details of the evidence and the committee's discussion are in evidence review A: investigation, management and follow-up of glioma.

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Why the committee made the recommendations

How the recommendations might affect practice

These recommendations reflect standard treatment for recurrent high-grade glioma, and therefore should not represent a substantial change in practice.

Full details of the evidence and the committee's discussion are in evidence review A: investigation, management and follow-up of glioma.

Return to recommendations

Why the committee made the recommendations

There was evidence that 5‑aminolevulinic acid (5‑ALA), intraoperative MRI and diffusion tensor imaging could improve either the extent or safety of resection (particularly the preservation of neurological function). The committee noted that a combination of techniques might be needed to optimise both the extent and safety of resection for a particular surgical plan. The committee concluded that the evidence for MRI could be generalised to intraoperative ultrasound on the basis of their clinical experience, and therefore that clinicians should be able to choose either technique depending on availability.

The evidence for awake craniotomy was equivocal (non-significant differences compared with surgery under general anaesthesia), therefore from the evidence it was not possible to conclude that awake craniotomy would benefit all people with glioma. This is in line with the committee's clinical experience that some people benefit from the procedure (in terms of preserving language, motor and visual function) but others are harmed – particularly from psychological effects which act as a contraindication to awake craniotomy. The committee described how better preoperative procedures could reduce the number of people distressed by the procedure.

How the recommendations might affect practice

Some techniques recommended by the committee require a very high level of intraoperative skill, and this might have resource implications for hospitals recruiting people with these specialist skills. There is significant variation in the current provision of psychological support for people before and during awake craniotomy, and implementing this could carry a high cost to an individual unit.

If a unit does not have access to intraoperative ultrasound or MRI, the cost of acquiring this equipment could be substantial (MRI is relatively expensive, ultrasound is relatively cheap). However the committee concluded that most units should have access to one or the other already. Therefore the only resource impact would be if a unit currently using intraoperative ultrasound decided that the additional evidence for preservation of neurological function in intraoperative MRI justified the cost of switching machines. However, the committee thought this was unlikely to happen.

Using 5‑ALA is associated with a high cost, and 5‑ALA-guided surgery needs a non-standard fluorescence-detecting microscope. Therefore the resource impact of this recommendation is likely to be high in all settings, and very high in settings without access to a fluorescence-detecting microscope. The anticipated resource impact of this recommendation is greater than £1 million per year.

Full details of the evidence and the committee's discussion are in evidence review A: investigation, management and follow-up of glioma.

Return to recommendations

Why the committee made the recommendations

In the absence of evidence, the committee made recommendations based on their clinical experience. They recommended regular clinical review as the only plausible way of identifying and potentially managing recurrence or changing symptoms. They also recommended the review schedule take into account all of the person's relevant characteristics, including grade of tumour. As this is quite difficult to work out, the committee suggested a schedule of clinical reviews that is likely to be beneficial for a 'typical' person, which can be amended as needed to take into account individual variation. The committee did not uncover evidence on who should do the follow‑up and so did not make a recommendation on this topic as it would vary according to clinical need, but discussed how it could be – for example – the local oncologist, neuro-oncologist, neurologist, neurosurgeon, clinical nurse specialist or GP.

As regular clinical review should include imaging, based on their experience the committee suggested an MRI sequence which they believed would be suitable to monitor for recurrence. They discussed how advanced MRI techniques might be valuable, but as these techniques are time-consuming and difficult to interpret the committee concluded they should only be recommended under certain circumstances where extra information was likely to substantially alter treatment plans. The committee recommended that any change in neurological signs or symptoms (which would include changes in behavioural, emotional and psychological signs and symptoms) be treated as a sign of a potential change to the tumour, and therefore recommended clinical review outside the usual schedule in order to investigate this.

The committee believed that a dedicated supportive care clinic could improve outcomes for people with low-grade glioma, but did not find any evidence on this. Therefore they made a research recommendation on improving the long-term outcomes of people with low-grade glioma.

How the recommendations might affect practice

The recommendations are in line with current best practice, and should standardise practice. They are unlikely to cause a significant increase in resource use, but there may be some additional costs or changes in service configuration if practice differs in a particular centre.

The imaging sequences are recommended on the basis of evidence for the appropriate sequences for initial diagnosis, and so might not be the standard sequence for follow‑up in all centres. As a result, adopting the recommended sequences might create some additional workload for some centres. However the recommendations for exact schedules are examples based on consensus in the committee, and there is therefore flexibility for centres to adapt these to their own models, limiting resource impact.

Full details of the evidence and the committee's discussion are in evidence review A: investigation, management and follow-up of glioma.

Return to recommendations

Why the committee made the recommendations

Evidence indicated that standard structural MRI is useful in distinguishing high-grade from low-grade glioma, and the committee agreed that it is appropriate to extrapolate from this evidence to a belief that MRI can be used to distinguish meningioma from healthy brain tissue. In the committee's experience, CT scans can be more accurate than MRI for assessing meningioma with bone involvement.

How the recommendations might affect practice

Currently, various imaging strategies are used depending on the centre and the person's circumstances. These recommendations aim to reduce variation in practice, and ensure that images obtained at different sites and using different equipment can be more accurately compared. Some centres may need to change their imaging protocols as a result, but this should not require the purchase of additional equipment.

Full details of the evidence and the committee's discussion are in evidence review B: investigation, management and follow-up of meningioma.

Return to recommendations

Why the committee made the recommendations

Based on limited evidence and their clinical experience, the committee concluded that management of this group of meningiomas will depend on the type of meningioma. They noted that evidence for 1 grade of meningioma could not normally be used to suggest best management for another grade. Therefore the committee made recommendations for each grade of meningioma separately, using evidence if this was available and their judgement if it was not. The committee identified that management could be more conservative if the tumour grade was lower and initial resection more complete, and should be more aggressive if the tumour grade was higher or initial resection more partial.

The committee agreed that the 3 management options – further radiotherapy, surgery and active monitoring – had different balances of benefits and harms in different situations. However they also agreed that serious harm could be done to a person with a tumour if they were over- or under-treated given the risk profile of their tumour, and so made recommendations according to this risk. For example, for a low-grade almost completely-resected tumour (grade I, Simpson 2 excision), radiotherapy or further surgery could expose the person to risk of harm for no expected clinical gain.

Based on limited evidence, the committee made recommendations on how to deliver radiotherapy or radiosurgery where this was appropriate. They used their experience to highlight features of the tumour or preferences of the person that might help select the most appropriate radiotherapy or radiosurgery modality, and explained that the best results would come through minimising the dose of radiation delivered to healthy brain tissue while maximising the chance of local control.

The committee were unable to find evidence comparing different timings of radiotherapy in incompletely excised grade I meningioma. As the disease is slow growing it can be difficult to assess the risks of immediate side effects from treatment compared to the longer-term benefits of tumour control. Therefore the committee made a research recommendation to investigate this topic.

How the recommendations might affect practice

The recommendations reflect standard practice in many centres, and should make treatment more consistent.

An appointment with an oncologist for all people who may have radiotherapy is not currently standard practice. However, for most people this is likely to mean a change in the timing of their first appointment with an oncologist, rather than many more people having oncologist appointments.

Full details of the evidence and the committee's discussion are in evidence review B: investigation, management and follow-up of meningioma.

Return to recommendations

Why the committee made the recommendations

In the absence of evidence, the committee made recommendations based on their clinical experience. They recommended regular clinical review as the only plausible way of identifying and potentially managing recurrence or changing symptoms. They also recommended the review schedule take into account all of the person's relevant characteristics, including grade of tumour. As this is quite difficult to work out, the committee suggested a schedule of clinical reviews that is likely to be beneficial for a 'typical' person, which can be amended as needed to take into account individual variation. The committee did not uncover evidence on who should do the follow‑up and so did not make a recommendation on this topic as it would vary according to clinical need, but discussed how it could be – for example – the local oncologist, neuro-oncologist, neurologist, neurosurgeon, clinical nurse specialist or GP.

As regular clinical review should include imaging, based on their experience the committee suggested an MRI sequence which they believed would be suitable to monitor for recurrence. They discussed how advanced MRI techniques might be valuable, but as these techniques are time-consuming and difficult to interpret the committee concluded they should only be recommended under certain circumstances where extra information was likely to substantially alter treatment plans. The committee recommended that any change in neurological signs or symptoms (which would include changes in behavioural, emotional and psychological signs and symptoms) be treated as a sign of a potential change to the tumour, and therefore recommended clinical review outside the usual schedule in order to investigate this.

How the recommendations might affect practice

The recommendations are in line with current best practice, and should standardise practice. They are unlikely to cause a significant increase in resource use, but there may be some additional costs or changes in service configuration if practice differs in a particular centre.

The imaging sequences are recommended on the basis of evidence for the appropriate sequences for initial diagnosis, and so might not be the standard sequence for follow‑up in all centres. As a result, adopting the recommended sequences might create some additional workload for some centres. However the recommendations for exact schedules are examples based on consensus in the committee, and there is therefore flexibility for centres to adapt these to their own models, limiting resource impact.

Full details of the evidence and the committee's discussion are in evidence review B: investigation, management and follow-up of meningioma.

Return to recommendations

Why the committee made the recommendations

In the absence of evidence, the committee recommended standard structural MRI based on their experience, because it is important to establish the exact number of metastases in the brain, which can guide further treatment. The committee described how failing to establish this could be dangerous. Extracranial imaging, biopsy of the extracranial disease (where indicated) and performing all imaging before multidisciplinary team discussions should ensure that all necessary information is available so that appropriate decisions are made and delays in treatment avoided.

How the recommendations might affect practice

The recommendations reinforce current best practice and should reduce delays to local intracranial treatment.

Full details of the evidence and the committee's discussion are in evidence review C: investigation, management and follow-up of brain metastases.

Return to recommendations

Why the committee made the recommendations

The committee made recommendations based on the available evidence and their judgement. They described how features of brain metastases, including the number and volume (which is important for establishing prognosis), should be evaluated before starting treatment, and decisions about treatment made on the basis of these features and the person's preferences.

The committee described how systematic anti-cancer therapies were widely used in the management of other types of metastases, and therefore they might be expected to work for brain tumours. In the absence of evidence, the committee recommended considering systematic anti-cancer therapies on the basis of their clinical experience. Whether or not these therapies should be given depends on the type of metastasis: if it is not likely to respond then the side effects would not justify giving the therapy, whereas if the metastasis was likely to respond then the therapy was likely to be beneficial.

Evidence indicated that surgery, stereotactic radiosurgery and stereotactic radiotherapy are effective for treating a single brain metastasis, but there was no evidence to recommend 1 technique over the other. There was some evidence that irradiation of the cavity site improved local control, so the committee recommended it on the basis that improving local control should improve quality of life.

January 2021: the recommendations on this surgical cavity radiosurgery and radiotherapy have been updated. For details see the update information.

For people with multiple brain metastases, the committee described how treatment options are more variable, and that resection, stereotactic radiosurgery, stereotactic radiotherapy and whole-brain radiotherapy could all be considered in certain circumstances.

The committee recommended that neither memantine nor concurrent systemic therapy should be offered to enhance the efficacy of whole-brain radiotherapy, on the basis of evidence of no benefit and a potential risk of harm. However, there were biological reasons to think these treatments might be beneficial in some settings, so the committee agreed these therapies could be offered in the context of a clinical trial to investigate this.

How the recommendations might affect practice

Current practice varies greatly between centres. Some of the variation reflects clinically relevant factors such as expertise in a particular technique or the patient population. The recommendations should help to standardise care and prevent some harmful and wasteful practices from continuing. Economic modelling identified that the recommendations will likely increase costs, but the committee believed that this was still an efficient use of NHS resources, as the improvement to quality of life was significant.

Full details of the evidence and the committee's discussion are in evidence review C: investigation, management and follow-up of brain metastases.

Return to recommendations

Why the committee made the recommendations

In the absence of evidence, the committee made recommendations based on their clinical experience. They recommended regular clinical review as the only plausible way of identifying and potentially managing recurrence or changing symptoms. They also recommended the review schedule take into account all of the person's relevant characteristics, including grade of tumour. As this is quite difficult to work out, the committee suggested a schedule of clinical reviews that is likely to be beneficial for a 'typical' person, which can be amended as needed to take into account individual variation. The committee did not uncover evidence on who should do the follow‑up and so did not make a recommendation on this topic as it would vary according to clinical need, but discussed how it could be – for example – the local oncologist, neuro-oncologist, neurologist, neurosurgeon, clinical nurse specialist or GP.

As regular clinical review should include imaging, based on their experience the committee suggested an MRI sequence which they believed would be suitable to monitor for recurrence. They discussed how advanced MRI techniques might be valuable, but as these techniques are time-consuming and difficult to interpret the committee concluded they should only be recommended under certain circumstances where extra information was likely to substantially alter treatment plans. The committee recommended that any change in neurological signs or symptoms (which would include changes in behavioural, emotional and psychological signs and symptoms) be treated as a sign of a potential change to the tumour, and therefore recommended clinical review outside the usual schedule in order to investigate this.

How the recommendations might affect practice

The recommendations are in line with current best practice, and should standardise practice. They are unlikely to cause a significant increase in resource use, but there may be some additional costs or changes in service configuration if practice differs in a particular centre.

The imaging sequences are recommended on the basis of evidence for the appropriate sequences for initial diagnosis, and so might not be the standard sequence for follow‑up in all centres. As a result, adopting the recommended sequences might create some additional workload for some centres. However the recommendations for exact schedules are examples based on consensus in the committee, and there is therefore flexibility for centres to adapt these to their own models, limiting resource impact.

Full details of the evidence and the committee's discussion are in evidence review C: investigation, management and follow-up of brain metastases.

Return to recommendations

Why the committee made the recommendations

Based on the evidence and their own experience, the committee determined that people with brain tumours have very specific needs that are often not met. In particular, they highlighted ways in which the care needs of people with brain tumours differ from those of people with other types of cancer, such as the impact on the person's sense of identity and legal requirements related to driving. Losing the ability or legal right to drive can have a profound effect on the patient's independence, employment status and self-esteem. The committee's aim was to improve the support and information offered to people with brain tumours.

The committee described how the care needs of people with brain tumours were often more complex than could be considered in a single guideline. In particular, young people, people wishing to preserve their fertility, and people nearing the end of their life have especially complex needs. In order to address these needs, the committee signposted to existing NICE guidance in the specific area.

How the recommendations might affect practice

The recommendations should improve care for both people living with brain tumours and their relatives and carers. It is likely that there will be a short-term resource impact in some areas, as supportive care for people with brain tumours is currently variable, with very little support available in some areas.

Full details of the evidence and the committee's discussion are in evidence review D: supporting people living with a brain tumour.

Return to recommendations

Why the committee made the recommendations

No evidence was found for this topic. Based on their experience, the committee agreed that neurological rehabilitation is likely to be suitable for many people with brain tumours. Given that neurological rehabilitation is time-consuming (especially if the person with a tumour lives a long way from the rehabilitation centre) and sometimes not appropriate, the committee agreed that assessment should be carried out at every stage of diagnosis and follow‑up to identify which, if any, forms of rehabilitation are suitable for the person. The aim of the recommendations is to ensure that neurological rehabilitation is considered at every stage of treatment and follow‑up.

How the recommendations might affect practice

There is currently variation in practice in assessing whether people with a brain tumour need neurological rehabilitation. Some of this reflects the availability of neurological rehabilitation services. The recommendations reinforce current best practice, and will mean a change in practice in some areas, including where assessment is 'ad hoc' rather than systematic.

People with a brain tumour make up a small percentage of people referred for neurological rehabilitation, so only a small increase in demand on resources is expected. There should not be any extra training needs because professionals already have the knowledge and skills to provide the services.

Full details of the evidence and the committee's discussion are in evidence review D: supporting people living with a brain tumour.

Return to recommendations

Why the committee made the recommendations

No evidence was found for this topic. Some people experience late effects after treatment for a brain tumour. With the possible exception of stroke risk it is unknown if these late effects can be prevented, but the committee agreed that any negative impact can be managed through clinical vigilance and referral into appropriate specialist monitoring pathways. The committee explained that it was important to consider referral for anyone at risk of late effects – not just those at 'high' risk – but that there may be no value in such a referral overall in lower risk groups.

How the recommendations might affect practice

The recommendations should not significantly alter practice, as they reflect common clinical practice.

Full details of the evidence and the committee's discussion are in evidence review D: supporting people living with a brain tumour.

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