Brain metastases

Initiatief: NVN Aantal modules: 24

Brain metastases - Symptomatic treatment of brain metastase


What management plan should be followed in the symptomatic treatment of brain metastases?

• which medication is available, and how should the medication be dosed?

• can prophylactic medication be administered?

• what are the interactions?

• what management should be followed in the palliative phase?

• what management should be followed in the (pre)terminal phase?



Treatment with corticosteroids
An oral dose of dexamethasone of 4 mg once daily (possibly the same dose s.c. or i.v.) is generally sufficient for patients with brain metastases and neurological symptoms. In severe situations (massive oedema, obstruction hydrocephalus, reduced consciousness or brain stem dysfunction), a bolus of 10 mg s.c. or i.v. is administered and a maintenance treatment of 8-16 mg orally once daily (possibly s.c. or i.v.). In the case of comedication with phenytoin or carbamazepine, an increase in the dose up to 8 mg once daily should be considered.

Dexamethasone is not prescribed for asymptomatic brain metastases.

Dexamethasone is prescribed before and during radiotherapy for the prevention or treatment of (an increase in) cerebral oedema in patients with neurological symptoms. This may be omitted in the absence of complaints. Where possible, corticosteroids are gradually reduced after radiotherapy within 2-3 weeks, on the basis of patients' complaints.

If administration of corticosteroids cannot be ceased or has be started again, one should apply the lowest possible effective dose. The side effects are primarily monitored clinically. Prophylaxis with respect to gastrointestinal problems using proton pump inhibitors is only necessary in case of relevant comedication (e.g. with NSAID's) or comorbidity (a history of gastritis, gastric ulcers, abdominal bleeding or abdominal perforation). Monitoring of serum glucose in asymptomatic patients without diabetes mellitus is not recommended.

Corticosteroids are continued in the terminal phase until ingestion of oral medication is no longer possible. It is not recommended to cease corticosteroids to allow for cerebral herniation and thus to hasten a patient's death.

Prevention and treatment of epilepsy
The use of antiepileptics in patients with brain metastases is not recommended, as long as a seizure has not occurred.

An epileptic seizure may be halted using benzodiazepines if necessary, after which patients are treated with antiepileptics. Valproic acid is the drug of first choice, on the basis of its effectiveness, side effect profile and interaction with other medications, followed by levetiracetam.

Use of enzyme-inducing antiepileptics (phenobarbital, phenytoin, carbamazepine) should be avoided as much as possible when using dexamethasone and cytostatics metabolised via cytochrome P450.

In case oral or intravenous administration is not possible while there is a strict indication for continuing administration of antiepileptics, valproic acid (the same dose as oral) may be administered rectally. Provision of clonazepam may occur through oral, sublingual, subcutaneous or intramuscular administration. Midazolam may be administered orally, as a nasal spray, subcutaneously or intramuscularly.

If headaches do not respond to paracetamol and/or corticosteroids, treatment with opioids (morphine, phentanyl or oxycodon) is recommended.

The treatment of delirium in patients with brain metastases consists of correcting precipitating factors (as much as possible), non-drug treatment (ensuring a restful, stable and safe environment) and drug treatment with haloperidol and possibly benzodiazepines.


Treatment with corticosteroids
Treatment of patients with brain metastases with corticosteroids leads to an improvement in symptomatology in 33-84% of cases. The effect is noticeable within a few days. An effect is more likely with increased intracranial pressure, (threatening) herniation and progressive and/or short-lasting focal deficits. There is no clear association between the amount of cerebral oedema and the response to corticosteroids.
Bezjak, 2002 (5);Oneschuk, 1998 (6);Ryken, 2010 (27);Sarin, 2003 (4)

A dose of 4 mg dexamethasone/day is as effective as 8 or 16 mg, provided there are no severe neurological issues (massive oedema, obstruction hydrocephalus, reduced consciousness and brain stem dysfunction).
Ryken, 2010 (27);Vecht, 1994 (7)

There does not appear to be a clear relation between the symptomatic response to corticosteroids and the symptomatic response to radiotherapy.
Bezjak, 2002 (5)

Treatment with dexamethasone before and during radiotherapy leads to improvement in existing neurological symptoms.
Borgelt, 1980 (9);Bezjak, 2002 (5)

Corticosteroids may be ceased within a few weeks after radiotherapy in most patients.
Weissman, 1991 (1)

Treatment with corticosteroids is usually accompanied with (sometimes severe) side effects. The severity and number of side effects is dependent on the dose and duration of treatment.
Hempen, 2002 (11);Oneschuk, 1998 (6);Sarin, 2003 (4);Sturdza, 2008 (12);Vecht, 1994 (7)

Prevention and treatment of epilepsy
Preventative treatment with antiepileptics in patients with brain metastases does not influence the occurrence of seizures.
Valproic acid, phenytoin and carbamazepine are equally effective in the treatment of localisation-bound epilepsy with brain metastases.
Epilepsy Guideline Development Group, 2006

There is no certainty about the benefit of prophylaxis with antiepileptics in the first week after a craniotomy for brain metastases.
Kuijlen, 1996 (22);Mauro, 2007 (23);Sirven, 2004 (24);Temkin, 2002 (21)

Enzyme-inducing antiepileptics (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) have a strong interaction with cytostatics that are metabolised via the cytochrome P450 system, and also with corticosteroids, resulting in a reduced efficacy of both drugs.
Epilepsy Guideline Development group, 2006

Treatment with corticosteroids
Corticosteroids are used to reduce cerebral oedema and hence the symptoms resulting from brain metastases. Dexamethasone is the most commonly used and most studied corticosteroid in the treatment of brain metastases. The working mechanism of dexamethasone is presumably based on a reduction in capillary permeability and/or increased transport of sodium and water across the endothelial cells in the brain.

There is no comparative study between dexamethasone and prednisone in patients with brain metastases. Dexamethasone has less mineralcorticoid effects and would therefore less likely lead to fluid retention. The biological half-life of dexamethasone is 36-72 hours; a dosage frequency of 1x per day therefore seems sufficient, although no research has been performed on this. A dose of 2x daily instead of 4x daily has been found to be effective (Weissman, 1991 (1)). The classic antiepileptics (phenytoin and carbamazepine) result in increased breakdown of dexamethasone (Gattis, 1996 (2)) through induction of the cytochrome P450 system.

No placebo-controlled study has been performed on the effect of dexamethasone for brain metastases. The symptomatic response percentages in case series vary from 33-84% (Wolfson, 1994 (3);Sarin, 2003 (4);Bezjak, 2002 (5)). The response criteria are not well specified in many studies. In a prospective study with specified neurological criteria, only 4 out of 12 patients (33%) had a response (Wolfson, 1994 (3)). In a larger prospective study on the effect of radiotherapy on brain metastases, 63 out of 75 patients (84%) showed neurological improvement after treatment with dexamethasone (and before radiotherapy was administered) (Bezjak, 2002 (5)). There was no relationship between the level of oedema detected by imaging and the response to steroids in this study. The effect of corticosteroids is usually noticeable within 24-48 hours and the maximum effect is observed after 3-7 days (Oneschuk, 1998 (6);Sarin, 2003 (4)). Response is more likely with increased intracranial pressure and/or threatening herniation and with progressive and/or short-lasting focal deficits (Oneschuk, 1998 (6);Sarin, 2003 (4)). It is sometimes assumed that the response to corticosteroids is predictive of the response to radiotherapy. In the study by Bezjak, however, no relationship was observed between the symptomatic response to corticosteroids and the symptomatic response to radiotherapy (Bezjak, 2002 (5)).

One comparative study has been performed on the effects of dexamethasone dosage (Vecht, 1994 (7)). In this study, 4 mg/day dexamethasone appeared equally effective in improving the KPS as 8 or 16 mg/day dexamethasone, provided that patients had no (threatening) herniation. It has not been studied to what extent administration of a bolus and dosages >4 mg/day are necessary and effective in severe situations (massive oedema, obstruction hydrocephalus, reduced consciousness and brain stem dysfunction); this often occurs in practice. Patients in these situations were excluded in the study.

Corticosteroids are often administered to prevent or treat (an increase in) cerebral oedema in case of brain metastases during radiotherapy (Millar, 2004 (8)). There is only one randomised study that compared radiotherapy for brain metastases with or without corticosteroids (Wolfson, 1994 (3)); however, the number of patients included (12) was too small to draw conclusions. In a study by the RTOG, 30% of patients did not receive corticosteroids during radiotherapy for unspecified reasons (Borgelt, 1980 (9)); in the subgroup of patients with neurological symptoms, more improvement was observed in those treated with corticosteroids.

The ECOG performed a randomised study in 47 patients with brain metastases, in which patients were randomised between treatment with corticosteroids only and treatment with corticosteroids followed by radiotherapy (Horton, 1971 (10)). The duration of the neurological response was longer when corticosteroids were combined with radiotherapy.

After completing radiotherapy, the corticosteroids are gradually reduced and ceased where possible. In two studies, the patients used corticosteroids for an average of 6-7 weeks (Hempen, 2002 (11);Sturdza, 2008 (12)). A study by Weissman shows that it is possible to reduce and cease corticosteroids within 2-3 weeks (Weissman, 1991 (1)). For approximately 20% of patients, it appears not possible, even in the long-term, to cease corticosteroid use (Cairncross, 1980 (13);Hempen, 2002 (11)).

In approximately 80% of cases, treatment with corticosteroids is accompanied with (sometimes debilitating) side effects (Hempen, 2002 (11);Oneschuk, 1998 (6);Sarin, 2003 (4);Sturdza, 2008 (12);Vecht, 1994 (7)). The number and severity of the side effects is dependent on the dose (more side effects with 8 and 16 mg dexamethasone/day than with 4 mg/day) and the duration of treatment (more with a duration >3 weeks). The percentages of side effects reported vary highly due to the fact that these factors differ per study, side effects are often not systematically registered, and some studies also included patients with primary brain tumours (who often have a longer survival and therefore may have other side effects as well) (Batchelor, 1997 (14);Hempen, 2002 (11);Sturdza, 2008 (12),Vecht, 1994 (7)):

  • Cushing's face
  • hyperglycaemia and diabetes mellitus
  • proximal muscle weakness
  • increased appetite
  • insomnia
  • psychological problems (dysphoria, depression, anxiety, psychosis)
  • peripheral oedema
  • infections
  • gastro-intestinal complaints, particularly abdominal complaints, bleeding and perforation
  • oral candidiasis
  • weight gain
  • hiccups
  • changed sense of taste
  • accomodation disorder
  • tremor

All the side effects mentioned above are almost always reversible.
Given the side effects and their relationship with treatment dose and duration, it is recommended that corticosteroids are used in as low a dose and as short a time-frame as possible. If corticosteroids have been used shorter than 2-3 weeks, treatment may be ceased all at once. When gradually reducing dexamethasone, unpleasant joint complaints may occur, especially in the knees. These are treated with NSAIDs (in combination with a proton pump inhibitor).

Aside from reducing the dexamethasone, the only possible treatment of the often debilitating myopathia with proximal muscle weakness is exercise therapy or mobilising exercises.

The relationship between the use of corticosteroids and gastrointestinal complaints is up for discussion (Conn, 1985 (15);Sarin, 2003 (4)). The risk is probably only increased in the presence of other risk factors (gastric ulcers, abdominal bleeding or abdominal perforation in the patient history or relevant comedication) and possibly even then only with high doses (>4 mg dexamethasone/day) (Conn, 1985 (15)). In this case, the use of a proton pump inhibitor is recommended.

Almost no systematic research has been performed on the necessity for early detection and treatment of hyperglycaemia during dexamethasone use. In part because of the short life expectancy of patients with brain metastases, it appears that routine monitoring of serum glucose is only necessary in patients with diabetes mellitus or in case of long-term use of high doses (>4 mg/day) of dexamethasone.

Sometimes it may not be possible to cease or recommence corticosteroid treatment in case of recurrence or progression of brain metastases. Cessation of corticosteroid treatment is sometimes considered in the terminal phase with the implication or intention that (an increase in) cerebral oedema and herniation will occur, and this will hasten the patient's death. No research has been conducted on this. Practice shows that an increase in cerebral oedema and rapid death is more of an exception than the rule (de Graeff, 2010 (16)). A possible explanation is that patients in the terminal phase are relatively dehydrated and cerebral oedema is therefore less likely to occur.

If a patient in the terminal phase is no longer able to ingest oral medication, the question is whether it is necessary and worthwhile to continue the dexamethasone parenterally (subcutaneously or intravenously). This does not appear necessary given the very short life expectancy (shorter than several days) (de Graeff, 2010 (16)).

Prevention and treatment of epilepsy
Epileptic seizures occur in 10-25% of patients with brain metastases as presenting symptom and up to 40% in the further course of the disease. The risk of neurological deficit and progression to a life-threatening epileptic status, and the impact of seizures on the quality of life are clear indications for treatment with antiepileptics. In principle, treatment is no different from that of non-tumour associated symptomatic epilepsy, where the severity of the seizures (frequency and type) and side effects of antiepileptics play an important role in drug treatment.

Prophylactic treatment with antiepileptics does not influence the incidence of seizures (Forsyth, 2003 (17);Glantz, 1996 (18);Glantz, 2000 (19)) and is therefore not indicated. The same applies to prophylaxis with antiepileptics more than a week after craniotomy for a brain metastasis (Foy, 1992 (20);Temkin, 2002 (21)). There is no certainty about the benefit of prophylaxis in the direct (<7 days) postoperative phase (Kuijlen, 1996 (22);Mauro, 2007 (23);Sirven, 2004 (24);Temkin, 2002 (21)).

Epileptic seizures are halted with a benzodiazepine, followed by treatment with valproic acid. There is no difference in effectiveness between valproic acid, phenytoin, lamotrigine, oxcarbazepine and carbamazepine for treatment of secondary generalised epilepsy (Epilepsy Guideline Development Group, 2006). Levetiracetam is probably equally effective, but this has been less extensively researched (Brodie 2007 (25)). A disadvantage of the use of phenytoin, oxcarbazepine and carbamazepine is the negative interaction between especially phenytoin and corticosteroids and between phenytoin, oxcarbazepine and carbamazepine with many cytostatics, resulting in a reduced efficacy of antiepileptics and chemotherapy. Phenytoin is no longer recommended due to its side-effects profile (Epilepsy Guideline Development Group, 2006). Lamotrigine has the disadvantage that it requires a gradual dose escalation due to a risk of skin reactions. A slow increase is often undesirable in the event of a recently occurred seizure as a result of brain metastasis. In addition, lamotrigine has a moderate enzyme-inducing effect.

Valproic acid derivates may influence thrombocyte function and prolong bleeding time, but it is uncertain whether these effects are clinically relevant. In addition, they may also (in some cases) cause thrombocytopenia. The newer antiepileptics levetiracetam and gabapentine do not interact with cytostatics. It is not known whether these drugs are as effective as a monotherapeutic agent as valproic acid.

Long-lasting focal seizures (>30 minutes) and a convulsive epileptic status (>5 minutes) are life-threatening and should be halted in the usual manner (diazepam 10 mg rectiole, or midazolam 5-10 mg orally, via a nasal spray or s.c., clonazepam 0.5-2 mg i.v., or lorazepam 2-4 mg i.v., followed by valproic acid i.v. or possibly phenytoin i.v. if required).

Side effects of antiepileptics may severely affect quality of life. Common adverse effects are:

  • from valproic acid: nausea, insomnia, weight gain, tremor and sometimes thrombopenia and thrombopathia
  • from carbamazepine: nausea, insomnia, diplopia, leukopenia, thrombopenia and hyponaetremia
  • from levetiracetam: mood disorders and nausea
  • from gabapentine: mainly insomnia and dizziness

Benzodiazepines, valproic acid and levetiracetam (and possibly phenytoin) may be administered intravenously (in the same dose) if necessary.

Alternatives for oral or intravenous administration are rectal, subcutaneous or possibly intramuscular administrations. Valproic acid may be administered rectally as a gel capsule (Propymal®, Convulex®) in the same dose as oral administration. Oral, sublingual, subcutaneous or intramuscular administration of clonazepam is an option in the standard dose. Clonazepam is not officially registered for oral, sublingual and subcutaneous administration. Midazolam may be administered orally, as a nasal spray, subcutaneously or intramuscularly.

Headache is observed in 25-50% of patients with brain metastases. It is usually caused by an increase in intracranial pressure, but other factors such as metabolic disorders and psychological factors may also play a role. Tumour-related headache is usually accompanied with neurological deficits, relatively often with nausea and vomiting, and often worsens with bending over or a pressure increase (coughing, sneezing or straining). The characteristic morning headache that improves after getting up is seen in less than half of patients with brain metastases and headache.

Research regarding the efficacy of drug-based treatment has not been performed. Paracetamol may sometimes be effective. In many cases, there is an improvement after treatment with corticosteroids. If this is not the case, treatment with opioids (morphine, phentanyl or oxycodon) is recommended (de Graeff, 2010_HM). Treatment with NSAIDs is not recommended given the risk of abdominal problems with concomitant administration of corticosteroids.

Both the brain metastases and treatment with corticosteroids are precipitating factors for the development of a delirium (Bannink, 2010 (26)). Prior neurosurgery or radiotherapy of the cerebrum is a predisposing factor. Given the context of the patient with brain metastases, other precipitating factors are often present, such as medication (especially opioids and drugs with anticholinergic (side) effects) infections, electrolyte disorders, hypoxia etc. No systematic study has been performed on the treatment of a delirium resulting from brain metastases. Treatment is no different from other forms of therapies for a delirium in the palliative phase and consists of correcting precipitating factors (where possible) and symptomatic non-drug based as well as drug-based treatment (Bannink, 2010 (26)).

  1. 1 - Weissman DE, Janjan NA, Erickson B, Wilson FJ, Greenberg M, Ritch PS, et al. Twice-daily tapering dexamethasone treatment during cranial radiation for newly diagnosed brain metastases. J Neurooncol 1991 Dec;11(3):235-9.
  2. 2 - Gattis WA, May DB. Possible interaction involving phenytoin, dexamethasone, and antineoplastic agents: a case report and review. Ann Pharmacother 1996 May;30(5):520-6.
  3. 3 - Wolfson AH, Snodgrass SM, Schwade JG, Markoe AM, Landy H, Feun LG, et al. The role of steroids in the management of metastatic carcinoma to the brain. A pilot prospective trial. Am J Clin Oncol 1994 Jun;17(3):234-8.
  4. 4 - Sarin R, Murthy V. Medical decompressive therapy for primary and metastatic intracranial tumours. Lancet Neurol 2003 Jun;2(6):357-65.
  5. 5 - Bezjak A, Adam J, Barton R, Panzarella T, Laperriere N, Wong CS, et al. Symptom response after palliative radiotherapy for patients with brain metastases. Eur J Cancer 2002 Mar;38(4):487-96.
  6. 6 - Oneschuk D, Bruera E. Palliative management of brain metastases. Support Care Cancer 1998 Jul;6(4):365-72.
  7. 7 - Vecht CJ, Hovestadt A, Verbiest HB, van Vliet JJ, van Putten WL. Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. Neurology 1994 Apr;44(4):675-80.
  8. 8 - Millar BM, Bezjak A, Tsao M, Sturdza A, Laperriere N. Defining the impact and contribution of steroids in patients receiving whole-brain irradiation for cerebral metastases. Clin Oncol (R Coll Radiol ) 2004 Aug;16(5):339-44.
  9. 9 - Borgelt B, Gelber R, Kramer S, Brady LW, Chang CH, Davis LW, et al. The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1980 Jan;6(1):1-9.
  10. 10 - Horton J, Baxter DH, Olson KB. The management of metastases to the brain by irradiation and corticosteroids. Am J Roentgenol Radium Ther Nucl Med 1971 Feb;111(2):334-6.
  11. 11 - Hempen C, Weiss E, Hess CF. Dexamethasone treatment in patients with brain metastases and primary brain tumors: do the benefits outweigh the side-effects? Support Care Cancer 2002 May;10(4):322-8.
  12. 12 - Sturdza A, Millar BA, Bana N, Laperriere N, Pond G, Wong RK, et al. The use and toxicity of steroids in the management of patients with brain metastases. Support Care Cancer 2008 Sep;16(9):1041-8.
  13. 13 - Cairncross JG, Kim JH, Posner JB. Radiation therapy for brain metastases. Ann Neurol 1980 Jun;7(6):529-41.
  14. 14 - Batchelor TT, Taylor LP, Thaler HT, Posner JB, DeAngelis LM. Steroid myopathy in cancer patients. Neurology 1997 May;48(5):1234-8.
  15. 15 - Conn HO, Poynard T. Adrenocorticosteroid administration and peptic ulcer: a critical analysis. J Chronic Dis 1985;38(6):457-68.
  16. 16 - De Graeff A, Gijtenbeek A, Bossmann S. Richtlijn hersenmetastasen. Palliatieve zorg: richtlijnen voor de praktijk 2010 [cited 2010 Oct 15];Available from: URL:
  17. 17 - Forsyth PA, Weaver S, Fulton D, Brasher PM, Sutherland G, Stewart D, et al. Prophylactic anticonvulsants in patients with brain tumour. Can J Neurol Sci 2003 May;30(2):106-12.
  18. 18 - Glantz MJ, Cole BF, Friedberg MH, Lathi E, Choy H, Furie K, et al. A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors. Neurology 1996 Apr;46(4):985-91.
  19. 19 - Glantz MJ, Cole BF, Forsyth PA, Recht LD, Wen PY, Chamberlain MC, et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000 May 23;54(10):1886-93.
  20. 20 - Foy PM, Chadwick DW, Rajgopalan N, Johnson AL, Shaw MD. Do prophylactic anticonvulsant drugs alter the pattern of seizures after craniotomy? J Neurol Neurosurg Psychiatry 1992 Sep;55(9):753-7.
  21. 21 - Temkin NR. Prophylactic Anticonvulsants After Neurosurgery. Epilepsy Curr 2002 Jul;2(4):105-7.
  22. 22 - Kuijlen JM, Teernstra OP, Kessels AG, Herpers MJ, Beuls EA. Effectiveness of antiepileptic prophylaxis used with supratentorial craniotomies: a meta-analysis. Seizure 1996 Dec;5(4):291-8.
  23. 23 - Mauro AM, Bomprezzi C, Morresi S, Provinciali L, Formica F, Iacoangeli M, et al. Prevention of early postoperative seizures in patients with primary brain tumors: preliminary experience with oxcarbazepine. J Neurooncol 2007 Feb;81(3):279-85.
  24. 24 - Sirven JI, Wingerchuk DM, Drazkowski JF, Lyons MK, Zimmerman RS. Seizure prophylaxis in patients with brain tumors: a meta-analysis. Mayo Clin Proc 2004 Dec;79(12):1489-94.
  25. 25 - Brodie MJ, Perucca E, Ryvlin P, Ben-Menachem E, Meencke HJ. Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology 2007 Feb 6;68(6):402-8.
  26. 26 - Bannink M, De Graeff A, Monster M. Richtlijn delier. Palliatieve zorg: richtlijnen voor de praktijk 2010 [cited 2010 Oct 15];Available from: URL:
  27. 27 - Ryken TC, McDermott M, Robinson PD, Ammirati M, Andrews DW, Asher AL, et al. The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2010 Jan;96(1):103-14.

Authorization date and validity

Last review  : 01-07-2011

Last authorization  : 01-07-2011

The period of validity of the guideline (maximum of 5 years) is being monitored by IKNL. For various reasons, it may be necessary to revise the guideline earlier than intended. Sections of the guideline will be amended in the interim, when required.

Initiative and authorization

  • Nederlandse Vereniging voor Neurologie
Authorized by:
  • Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose
  • Nederlandse Vereniging voor Medische Oncologie
  • Nederlandse Vereniging voor Neurochirurgie
  • Nederlandse Vereniging voor Neurologie
  • Nederlandse Vereniging voor Radiotherapie en Oncologie
  • Verpleegkundigen en Verzorgenden Nederland
  • Nederlandse Vereniging voor Psychosociale Oncologie
  • Nederlands Instituut van Psychologen

Scope and target group


The guideline covers the processes of diagnosis, treatment, information provision and guidance of adult patients with metastases in the brain originating from solid tumours, thereby focusing on topical clinical problems encountered in daily practice. The guideline's recommendations aim to aid practitioners in their decision-making support when facing these problems. The recommendations are based on the highest available grade of scientific evidence and on consensus within the guideline development group. The guideline provides information on how the recommendations have been reached from the evidence.


The guideline may be used to provide information to patients and offers points of reference for transmural agreements or local protocols to facilitate implementation.


The guideline is intended for all professionals involved in the diagnostics, treatment and guidance of adult patients with brain metastases of solid tumours. These professionals include:

  • Primary specialists: neurologists, neurosurgeons, radiotherapists, medical oncologists, pulmonologists, (oncology) nurses, general practitioners, specialists (working) in palliative care
  • Supporting specialists: radiologists, pathologists
  • Healthcare providers specialised in psychosocial care: social workers, psychologists, psychiatrists and geriatric medicine specialists


Samenstelling werkgroep



mw. dr. J.M.M. Gijtenbeek, neuroloog, Universitair Medisch Centrum St Radboud, Nijmegen

Other members:

dr. L.V. Beerepoot, medisch oncoloog, St. Elisabeth Ziekenhuis, Tilburg

dr. W. Boogerd, neuroloog, Nederlands Kanker Instituut / Antoni van Leeuwenhoekziekenhuis, Slotervaartziekenhuis, Amsterdam

mw. S. Bossmann, nurse practitioner, Universitair Medisch Centrum St Radboud Nijmegen

mw. dr. M. van Dijk, internist-oncoloog, Maastricht Universitair Medisch Centrum, Maastricht

mw. dr. A.C. Dingemans, longarts, Maastricht Universitair Medisch Centrum, Maastricht

mw. dr. C. van Es, radiotherapeut-oncoloog, Utrecht Universitair Medisch Centrum, Utrecht, niet actief betrokken (is betrokken geweest bij het initiëren van de werkgroep maar kon vanwege onvoorziene omstandigheden niet aan de totstandkoming van de richtlijn meewerken)

dr. A. de Graeff, medisch oncoloog, Utrecht Universitair Medisch Centrum, Utrecht

dr. P.E.J. Hanssens, radiotherapeut-oncoloog, Gamma Knife Centrum, Tilburg

dr. H.F.M. van der Heijden, longarts, Universitair Medisch Centrum St Radboud, Nijmegen

dr. M.A.A.M. Heesters, radiotherapeut-oncoloog Universitair Medisch Centrum Groningen, Groningen

dr. P.A. M. Hofman, neuroradioloog, Maastricht Universitair Medisch Centrum, Maastricht

dr. R.L.H. Jansen, medisch oncoloog, Maastricht Universitair Medisch Centrum, Maastricht, niet actief betrokken

drs. E. Kurt, neurochirurg, Medisch Centrum Alkmaar

dr. F. J. Lagerwaard, radiotherapeut-oncoloog, Vrije Universiteit Medisch Centrum, Amsterdam

mw. prof.dr. J.B. Prins, klinisch psycholoog, Universitair Medisch Centrum St Radboud, Nijmegen

drs. J.H.C. Voormolen, neurochirurg, Leids Universitair Medisch Centrum, Leiden

drs. V.K.Y. Ho, epidemioloog/procesbegeleider, Integraal Kankercentrum Nederland (IKNL), locatie Utrecht

mw. M.L. van de Kar, ambtelijk secretaris, Landelijke Werkgroep Neuro-Oncologie (LWNO), Bussum

Ondersteuning methodologie

mw. dr. M. Brink, epidemioloog, IKNL, locatie Utrecht

drs. J.M. van der Zwan, MSc, epidemiologisch onderzoeker, IKNL, locatie Enschede


Leden werkgroep voorgaande revisie (2004)

dr. R.H. Boerman, neuroloog, Rijnstate Ziekenhuis, Arnhem (voorzitter)

dr. W. Boogerd, neuroloog, Nederlands Kanker Instituut / Antoni van Leeuwenhoekziekenhuis, Slotervaartziekenhuis, Amsterdam

mw. dr. W.M.H. Eijkenboom, radiotherapeut-oncoloog, Daniel den Hoed Kliniek, Rotterdam

dr. P.E.J. Hanssens, radiotherapeut-oncoloog, Dr. Bernard Verbeeten Instituut, Tilburg

dr. R.L.H. Jansen, medisch oncoloog, Academisch Ziekenhuis Maastricht

dr. F. J. Lagerwaard, radiotherapeut-oncoloog, Vrije Universiteit Medisch Centrum, Amsterdam

prof.dr. C.J.A. Punt, inetrnist-oncoloog, Academisch Ziekenhuis Nijmegen

drs. J.H.C. Voormolen, neurochirurg, Leids Universitair Medisch Centrum, Leiden

prof.dr. J.T. Wilmink, neuroradioloog, Academisch Ziekenhuis Maastricht

dr. J.G. Wolbers, neurochirurg, Academisch Ziekenhuis Dijkzigt, Rotterdam



Declaration of interest

All guideline working group members were asked to fill in a conflict of interest declaration, in which they stated ties with the medical industry at the start and completing the guideline process. An overview of these conflict of interest declarations can be found below. The remaining guideline working group members have declared that at this moment or in the last three years they have not performed any activities on invitation or with subsidy/sponsoring by the medical industry.





Dr. L.V. Beerepoot




consultatie / advisering




Dr. W. Boogerd




Dr. M. van Dijk

Schering Plough



Dr. A.C. Dingemans




Astra Zeneca



consultatie / advisering / wetenschappelijk onderzoek

consultatie / advisering

consultatie / advisering / wetenschappelijk onderzoek

consultatie / advisering / wetenschappelijk onderzoek




Dr. C.A. van Es




Dr. A. de Graeff




consultatie / advisering

consultatie / advisering


Dr. P.A.M. Hofman

Strijker NL B.V.

Medtronics Spinal

Bayer Health Care

Johnson & Johnson






Dr. H.F.M. van der Heijden

Astra Zeneca

Sanofi Aventis




consultatie / advisering

consultatie / advisering

consultatie / advisering / wetenschappelijk onderzoek







Dr. R.L.H. Jansen



Sanofi Aventis

Diverse firma's



wetenschappelijk onderzoek





Dr. F.J. Lagerwaard

Roche Nederland

Roche NL-longadviesraad

Brain Lab

Varian Medical Systems

wetenschappelijk onderzoek

consultatie / advisering







Method of development

evidence based


Considerations concerning the implementation of the guideline as well as the feasibility of recommendations have been taken into account as much as possible in drafting the revised guideline.


The guideline is summarised and may be consulted in its entirety on The guideline has been brought to the attention of members of the LWNO, hospitals in the Netherlands, oncology commissions, as well as the scientific and professional associations involved. To further stimulate awareness and implementation of the guideline, regional tumour working groups on neuro-oncology of IKNL were invited to discuss its recommendations.


Given the highly progressive and unfavourable course of the disease, the guideline development group decided not to develop care indicators to measure the level of guideline implementation.