Brain metastases

Initiatief: NVN Aantal modules: 24

Brain metastases - Asymptomatic brain metastases


What management plan should be followed in patients with asymptomatic brain metastases?


Screening for asymptomatic brain metastases is only worthwhile with tumours that frequently metastasise to the brain and if the presence of brain metastases entails consequences for the treatment plan. Patients with asymptomatic brain metastases need not be excluded from clinical studies a priori.

Screening for asymptomatic brain metastases should be performed with the use of MRI. Neurological examination is not required if there are no complaints (on the basis of a good neurological history).

In general, treatment of asymptomatic brain metastases is only recommended if the metastases are assumed to give rise to complaints within the foreseeable future (large metastases, and/or localisation in eloquent areas including the brain stem, and/or substantial oedema), thus to prevent neurological symptoms. Survival is not influenced by earlier treatment. The considerations with respect to the different treatment possibilities do not substantially differ with those for symptomatic brain metastases.

In case of tumours sensitive to chemotherapy also exhibiting extracranial progression, systemic treatment (chemotherapy, hormonal therapy) may be considered in first instance. Depending on the expected systemic response, follow-up using a brain MRI scan should be performed after, for example, 3 courses or 2-3 months.

In case of a treatment indication for brain metastases and no systemic treatment is available, one may decide to perform neurosurgical resection, SRS and/or WBRT, depending on the size, the number and localisation of the metastases. The considerations for this are no different than those for symptomatic brain metastases.

Depending on the expectations with regard to the intracranial disease, the treatment possibilities in case of a recurrence/progression of the brain metastases and the wishes of the patient, one may opt for follow-up with MRI. The frequency of imaging depends on the abovementioned factors.


It is unclear whether early treatment of asymptomatic brain metastases has a favourable effect on quality of life. There are no adequate data on the long-term adverse effects of WBRT for asymptomatic brain metastases. In practice, the decision whether and how to treat the asymptomatic brain metastases depends on the clinical status of the patient, the extracranial activity of the tumour, the size and the number of brain metastases, the systemic treatment options and the treatment possibilities of the brain metastases.


Level 3
There are indications that neurological examination is of little added value for asymptomatic patients.
B: Hochstenbag, 2003 (5)

Level 2
It is plausible that the early treatment of asymptomatic brain metastases with WBRT does not entail a significant improvement in survival compared to the treatment of symptomatic brain metastases.
B: Mori, 1998 (22); Moscetti, 2007 (20)
C: Miller, 2003 (9)

Level 2
It is plausible that WBRT provides good intracranial control of asymptomatic brain metastases, although no improvement in survival has been demonstrated.
B: Niwinska, 2007 (12);Niwinska, 2010 (11);Sanchez de Cos, 2009 (18)
C: Miller, 2003 (9)

Level 2
It is plausible that SRS is a safe and effective treatment option for selected patients with (a limited number of) asymptomatic brain metastases.
B: Herfarth, 2003 (33);Kim, 1997 (19);Mori, 1998 (22);Yen, 2006 (23)
C: Hassaneen, 2009 (34)

Level 2
It is plausible that primary chemotherapy or treatment with EGFR tyrosine kinase inhibitors are adequate treatment options for synchronous asymptomatic brain metastases from NSCLC in case of active systemic disease. The response and overall survival after primary chemotherapy are not significantly different from primary WBRT.
B: Kim, 2009 (31);Lee, 2008 (30);Moscetti, 2007 (20)

Level 2
It is plausible that WBRT may be delayed or omitted in a selected group of patients with asymptomatic brain metastases (<2cm, not localised in eloquent areas including brain stem, little oedema) with a systemic response to chemotherapy.
B: Boogerd, 2007 (26);Kim, 2009 (31);Moscetti, 2007 (20)

Level 3
There are indications that temozolomide has limited effectiveness as monotherapy in patients with small (<2cm) brain metastases from melanoma.
B: Boogerd, 2007 (26);Schadendorf, 2006 (32)
C: Agarwala, 2004 (35)

Level 3
There are indications that primary chemotherapy for SCLC may have a greater effect on the primary tumour than on synchronous asymptomatic brain metastases.
A2: Seute, 2006 (21)

The incidence of asymptomatic brain metastases is unknown for most malignancies. They are more often diagnosed, however, given the increasing use of MRI, longer survival of cancer patients, and screening for participation in trials (Seute, 2008 (1);Yokoi, 1999 (2);Hochstenbag, 2000 (3);Carden, 2008 (4)). Optimal management of these brain metastases is therefore a relevant issue. The routine exclusion of patients with asymptomatic brain metastases from experimental clinical trials is probably no longer justified because this hinders research on new effective treatment of brain metastases (Carden, 2008 (4)). Patients with only a few small metastases that are not localised in eloquent areas or in the posterior cranial fossa would also be good candidates for a phase 1 study (Carden, 2008 (4)).

From the available literature, it can usually not be ascertained whether the assumption that a brain metastasis is asymptomatic is based on sound neurological history and examination. Incidentally, research in the Netherlands has demonstrated that examination performed by a neurologist has little added value for patients without complaints (Hochstenbag, 2003 (5)). Reported frequencies of asymptomatic brain metastases (demonstrated by MRI) are 11%-18% in SCLC (Seute, 2008 (1);Hochstenbag, 2000 (3);Taneja, 2007 (6)), 5-15% in NSCLC (Yokoi, 1999 (2);Hochstenbag, 2003 (5);Taneja, 2007 (6);Shi, 2006 (7);Jena, 2008 (8)) and 15% in metastatic breast carcinomas (Miller, 2003 (9)). Patients with an HER2/neu positive breast carcinoma, with a systemic response after treatment with trastuzumab (Herceptin), have an elevated risk of brain metastases (Gabos, 2006 (10);Niwinska, 2007 (11)). Thirty-four percent of patients (11 of 32) in a prospective study had asymptomatic brain metastases (Niwinska, 2007 (12)). Asymptomatic brain metastases were reported in 5% of patients with a melanoma (21% in stage IV) (Fogarty, 2006 (13)) and in 6% with metastatic renal cell carcinoma (Seaman, 1995 (14)). Given the relatively high incidence of asymptomatic brain metastases from NSCLC and HER2/neu positive stage IV breast carcinomas, phase 3 studies on the value of PCI are currently being performed with these groups. For the time being, MRI of the brain is only recommended when detection of synchronous brain metastases would alter the treatment plan regarding the primary tumour, such as in stage III NSCLC (Silvestri, 2007 (15)). The recent guideline on non-invasive staging of NSCLC (Silvestri, 2007 (15)) states that, excluding stage III, imaging is not required if the neurological history and examination are negative, given the small chance (0-10%) of finding brain metastases. Assumedly, the incidence of asymptomatic brain metastases is underestimated here because the guideline refers to CT studies. Ever since MRI became the imaging method of choice, the percentage of patients with asymptomatic brain metastases has been higher than was previously determined using CT (Seute, 2008 (1);Hochenstenbag, 2003 (5);Shi, 2006 (7)).

Given the high cumulative risk of brain metastases from SCLC (50% after 2 years), PCI is the standard treatment for all stages of SCLC with good response to chemotherapy (Auperin, 1999 (16);Slotman, 2007 (17)).PCI is not routinely preceded by imaging of the brain. See the SCLC guideline.

Prognostic factors
A few retrospective studies (Sanchez de Cos, 2009 (18);Kim, 1997 (19)) found that asymptomatic patients have a significantly longer survival than symptomatic patients (median survival 7.5 versus 4 months). This observation has been attributed to a lead-time bias: the survival appears longer due to early discovery of the metastases (Yokoi, 1999 (2)). In a recent small study of NSCLC (Sanchez de Cos, 2009 (18)), 12 asymptomatic patients were compared to 69 symptomatic patients. Asymptomatic patients had a significantly better performance status, were more frequently diagnosed with synchronous metastases, a larger number of metastases and also smaller metastases. Another survey found no difference in the number, size and localisation of the brain metastases between the two groups, nor in the presence of oedema or intratumoural bleeding (Jena, 2008 (8)). A good performance status (ECOG) and active treatment of both the primary tumour and brain metastases were the most important prognostic factors (Sanchez de Cos, 2009 (18)). Among patients with asymptomatic metastases, a larger percentage (80%) remained free from neurological complaints until the last visit or death compared to symptomatic patients (40%). However, most studies do not find a significant difference in survival. The majority of patients dies of progressive extracranial disease (Moscetti, 2007 (20);Seute, 2006 (21);Mori, 1998 (22);Yen, 2006 (23);Miller, 2003 (9)).

WBRT has been the treatment of choice for brain metastases for decades. Nowadays, SRS is often applied. Primary systemic treatment for asymptomatic brain metastases may be a treatment option for chemotherapy-sensitive systemic malignancies, if there is also extracranial progression. WBRT may then be delayed until clinical or radiological progression occurs(van den Bent, 2003 (24);Gerstner, 2007 (25);Boogerd, 2007 (26)).

Radiotherapy (also see WBRT)
Asymptomatic brain metastases were demonstrated in 23 of 155 (15%) extensively pretreated patients with a brain carcinoma, who were screened for participation in studies with angiogenesis inhibitors (Miller, 2003 (9)). Twenty-one patients were treated with WBRT and not a single patient developed symptoms. There was no difference in survival between patients with symptomatic and those with asymptomatic brain metastases (average survival of five months), survival for both groups was shorter than among patients without metastases (Miller, 2003 (9)). Twenty-six of the 29 symptomatic HER2/neu positive progressive patients with a breast carcinoma underwent WBRT, resulting in complete remission (CR) of the brain metastases in 7 (29%) and partial remission (PR) in 15 (63%) of patients. All patients were without neurological symptoms after three months. The median survival was nine months and this not different from a patient group with symptomatic metastases. The cause of death was cerebral progression in 16% of asymptomatic and in 48% of symptomatic patients (Niwinska, 2010 (11);Niwinska, 2007 (12)). Adverse effects of WBRT were not evaluated by these studies.
Possible damaging effects of WBRT play a role in the decision whether or not to apply PCI in selected patient groups that have a high risk of brain metastases. Prospective data on this matter is scarce (Grosshans, 2008 (27)). (Please also refer to the guideline on SCLC for indications for PCI). The neurocognitive effects of PCI were studied prospectively in 69 SCLC patients. Only 37 patients also underwent a formal neuropsychological examination during follow-up (Grosshans, 2008 (27)). At the time of pre-PCI, 69 patients had cognitive function disorders. Although there was a deterioration in the first 15 months after PCI in performing functions and language, this effect did not persist and no significant difference in neurocognitive functioning was found between pre- and post PCI (Grosshans, 2008 (27)). A high percentage (38%) of pre-PCI cognitive function disorders were also found in 13 patients with a SCLC. This was comparable to patients with brain metastases pre-WBRT while being significantly different from a control group (13%) (Welzel, 2008 (28)). Patients with and without brain metastases scored significantly worse in verbal memory tests 6-8 weeks after WBRT (Welzel, 2008 (28)). Ten patients with a breast carcinoma (stage III/IV) in remission after an aggressive chemotherapy schedule including autologous bone marrow transplantation underwent PCI according to the study protocol (Huang, 2009 (29)). Three of the 10 patients developed severe neurocognitive disorders, 9 months and 4 and 5 years after PCI.

Chemotherapy (also see systemic therapy of symptomatic brain metastases)
There are only a few studies, usually with patients with a lung carcinoma, that have reported on the effect of chemotherapy with asymptomatic brain metastases. From a retrospective analysis (Moscetti, 2007 (20)) and a randomised pilot study (Lee, 2008 (30)), it appears that primary chemotherapy (platinum-based; gemcitabine/vinorelbine) is an adequate treatment option for patients with a NSCLC and synchronous asymptomatic brain metastases. The retrospective analysis shows the decision tree of various oncology centres: primary chemotherapy is a more frequent choice in the case of synchronous asymptomatic brain metastases; symptomatic patients first receive WBRT (Moscetti, 2007 (20)). A comparison between the groups is not possible given selection bias (Moscetti, 2007 (20)). There was no difference in overall response rate and survival between primary chemotherapy followed by WBRT or primary WBRT followed by chemotherapy in a patient group in which the indication for WBRT was determined beforehand (Lee, 2008 (30)). No difference was found in the change in cognitive functioning: both groups showed a decline. There was a close correlation between intracranial and extracranial tumour response (Lee, 2008 (30)). Comparable results were found in a recent, small prospective study with EGFR tyrosine kinase inhibitors (gefitinib or erlotinib) as primary treatment for asymptomatic synchronous brain metastases from adenocarcinoma of the lung in Asian patients. The response rate was 73.9%. Eleven of the 23 patients still underwent WBRT after an average follow-up of 19.3 months (Kim, 2009 (31)).

Synchronous asymptomatic brain metastases from a SCLC and from other chemotherapy-sensitive tumours are currently regularly treated with primary systemic chemotherapy, and it is assumed that the response of brain metastases is comparable with the response of the primary tumour (van den Bent, 2003 (24);Gerstner, 2007 (25)). Whether this assumption is justified is unclear: the studies (including those with symptomatic brain metastases) are usually small and are conducted in selected patient groups (also see Systemic therapy of symptomatic brain metastases). The response of brain metastases to cyclophosphamide, doxorubicine and etoposide in a retrospective study of 24 patients with asymptomatic brain metastases from SCLC was only 27%, with an extracranial response of 73%. All patients were symptomatic during follow-up (average of 2.3 months after chemotherapy). There was no difference in survival between responders (of the brain metastases) and non-responders (Seute, 2006 (21)). In this study, the authors hypothesise whether the BBB may be less disturbed in case of small asymptomatic brain metastases, so that chemotherapy is unable to reach the metastases sufficiently. However, the fact that asymptomatic brain metastases also enhance with contrast should be considered a sign that the BBB is disturbed after all.

Melanomas frequently metastasise to the brain, with a reported frequency of 21% asymptomatic brain metastases in stage IV melanoma (Fogarty, 2006 (13)). In a prospective phase II trial, 45 patients with asymptomatic brain metastases from a melanoma were treated with temozolomide. This treatment had an extremely limited effect: two patients (4.4%) had a partial response, and the disease was stable in five patients (11.1%). Eighty-two percent of the patients were progressive eight weeks after starting treatment. The median survival was 3.5 months (Schadendorf, 2006 (32)). Eleven of the 13 patients with a melanoma with brain metastases (eight asymptomatic) and a systemic response to temozolomide with or without immunotherapy, also had response or stabilisation of the brain metastases. Of the original group of 52 patients with brain metastases (<2 cm, not localised in the brain stem, no corticosteroids required), 25% had a systemic response and 21% a response (including SD) of the brain metastases; 9% had an objective (CR+PR) response. The average time to neurological progression was seven months. Two patients were treated with WBRT after three and five months (Boogerd, 2007 (26)). It should be noted that temozolomide is not registered for the treatment of brain metastases from melanoma.

Radiosurgery (also see SRS)
Various studies have reported that SRS is a safe and effective treatment option for asymptomatic brain metastases (Yen, 2006 (23);Kim, 1997 (19);Herfarth, 2003 (33),Mori, 1998 (22);Hassaneen, 2009 (34)). Local tumour control rates are high. No new neurological deficits were observed in seven patients with asymptomatic brain stem metastasis from a renal cell carcinoma, in 41 of 52 asymptomatic patients with a melanoma, and in 17 of 18 patients with an asymptomatic brain stem metastasis from various cancer types (Mori, 1998 (22);Herfarth, 2003 (33);Yen, 2006 (23)). The absence of neurological symptoms was a prognostically significant factor for survival in 77 patients (17 asymptomatic) with NSCLC (Kim, 1997 (19)), but not in the 35 patients (7 asymptomatic) with a renal cell carcinoma (Mori, 1998 (22)), and in the 53 patients (18 asymptomatic) with a brain stem metastasis (Yen, 2006 (23)).

Click here for the evidence table.

  1. 1 - Seute T, Leffers P, ten Velde GP, Twijnstra A. Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI). Cancer 2008 Apr 15;112(8):1827-34.
  2. 2 - Yokoi K, Kamiya N, Matsuguma H, Machida S, Hirose T, Mori K, et al. Detection of brain metastasis in potentially operable non-small cell lung cancer: a comparison of CT and MRI. Chest 1999 Mar;115(3):714-9.
  3. 3 - Hochstenbag MM, Twijnstra A, Wilmink JT, Wouters EF, ten Velde GP. Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis. J Neurooncol 2000 Jul;48(3):243-8.
  4. 4 - Carden CP, Agarwal R, Saran F, Judson IR. Eligibility of patients with brain metastases for phase I trials: time for a rethink? Lancet Oncol 2008 Oct;9(10):1012-7.
  5. 5 - Hochstenbag MM, Twijnstra A, Hofman P, Wouters EF, ten Velde GP. MR-imaging of the brain of neurologic asymptomatic patients with large cell or adenocarcinoma of the lung. Does it influence prognosis and treatment? Lung Cancer 2003 Nov;42(2):189-93.
  6. 6 - Taneja S, Talwar V, Jena A, Doval DC. Incidence of asymptomatic brain metastasis in lung cancer patients at initial staging work-up – a study of 211 cases. JIACM 2007;8(4):312-5.
  7. 7 - Shi AA, Digumarthy SR, Temel JS, Halpern EF, Kuester LB, Aquino SL. Does initial staging or tumor histology better identify asymptomatic brain metastases in patients with non-small cell lung cancer? J Thorac Oncol 2006 Mar;1(3):205-10.
  8. 8 - Jena A, Taneja S, Talwar V, Sharma JB. Magnetic resonance (MR) patterns of brain metastasis in lung cancer patients: correlation of imaging findings with symptom. J Thorac Oncol 2008 Feb;3(2):140-4.
  9. 9 - Miller KD, Weathers T, Haney LG, Timmerman R, Dickler M, Shen J, et al. Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Ann Oncol 2003 Jul;14(7):1072-7.
  10. 10 - Gabos Z, Sinha R, Hanson J, Chauhan N, Hugh J, Mackey JR, et al. Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol 2006 Dec 20;24(36):5658-63.
  11. 11 - Niwinska A, Tacikowska M, Murawska M. The effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival and cause of death. Int J Radiat Oncol Biol Phys 2010 Jul 15;77(4):1134-9.
  12. 12 - Niwinska A, Tacikowska M, Pienkowski T. Occult brain metastases in HER2-positive breast cancer patients: frequency and response to radiotherapy. Acta Oncol 2007;46(7):1027-9.
  13. 13 - Fogarty GB, Tartaguia C. The utility of magnetic resonance imaging in the detection of brain metastases in the staging of cutaneous melanoma. Clin Oncol (R Coll Radiol ) 2006 May;18(4):360-2.
  14. 14 - Seaman EK, Ross S, Sawczuk IS. High incidence of asymptomatic brain lesions in metastatic renal cell carcinoma. J Neurooncol 1995;23(3):253-6.
  15. 15 - Silvestri GA, Gould MK, Margolis ML, Tanoue LT, McCrory D, Toloza E, et al. Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest 2007 Sep;132(3 Suppl):178S-201S.
  16. 16 - Auperin A, Arriagada R, Pignon JP, Le PC, Gregor A, Stephens RJ, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999 Aug 12;341(7):476-84.
  17. 17 - Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007 Aug 16;357(7):664-72.
  18. 18 - Sanchez de Cos J, Sojo Gonzalez MA, Montero MV, Perez Calvo MC, Vicente MJ, Valle MH. Non-small cell lung cancer and silent brain metastasis. Survival and prognostic factors. Lung Cancer 2009 Jan;63(1):140-5.
  19. 19 - Kim YS, Kondziolka D, Flickinger JC, Lunsford LD. Stereotactic radiosurgery for patients with nonsmall cell lung carcinoma metastatic to the brain. Cancer 1997 Dec 1;80(11):2075-83.
  20. 20 - Moscetti L, Nelli F, Felici A, Rinaldi M, De SS, D'Auria G, et al. Up-front chemotherapy and radiation treatment in newly diagnosed nonsmall cell lung cancer with brain metastases: survey by Outcome Research Network for Evaluation of Treatment Results in Oncology. Cancer 2007 Jan 15;109(2):274-81.
  21. 21 - Seute T, Leffers P, Wilmink JT, ten Velde GP, Twijnstra A. Response of asymptomatic brain metastases from small-cell lung cancer to systemic first-line chemotherapy. J Clin Oncol 2006 May 1;24(13):2079-83.
  22. 22 - Mori Y, Kondziolka D, Flickinger JC, Logan T, Lunsford LD. Stereotactic radiosurgery for brain metastasis from renal cell carcinoma. Cancer 1998 Jul 15;83(2):344-53.
  23. 23 - Yen CP, Sheehan J, Patterson G, Steiner L. Gamma knife surgery for metastatic brainstem tumors. J Neurosurg 2006 Aug;105(2):213-9.
  24. 24 - van den Bent MJ. The role of chemotherapy in brain metastases. Eur J Cancer 2003 Oct;39(15):2114-20.
  25. 25 - Gerstner ER, Fine RL. Increased permeability of the blood-brain barrier to chemotherapy in metastatic brain tumors: establishing a treatment paradigm. J Clin Oncol 2007 Jun 1;25(16):2306-12.
  26. 26 - Boogerd W, de Gast GC, Dalesio O. Temozolomide in advanced malignant melanoma with small brain metastases: can we withhold cranial irradiation? Cancer 2007 Jan 15;109(2):306-12.
  27. 27 - Grosshans DR, Meyers CA, Allen PK, Davenport SD, Komaki R. Neurocognitive function in patients with small cell lung cancer: effect of prophylactic cranial irradiation. Cancer 2008 Feb 1;112(3):589-95.
  28. 28 - Welzel G, Fleckenstein K, Schaefer J, Hermann B, Kraus-Tiefenbacher U, Mai SK, et al. Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys 2008 Dec 1;72(5):1311-8.
  29. 29 - Huang F, Alrefae M, Langleben A, Roberge D. Prophylactic cranial irradiation in advanced breast cancer: a case for caution. Int J Radiat Oncol Biol Phys 2009 Mar 1;73(3):752-8.
  30. 30 - Lee DH, Han JY, Kim HT, Yoon SJ, Pyo HR, Cho KH, et al. Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first : result of a randomized pilot study. Cancer 2008 Jul 1;113(1):143-9.
  31. 31 - Kim JE, Lee DH, Choi Y, Yoon DH, Kim SW, Suh C, et al. Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis. Lung Cancer 2009 Sep;65(3):351-4.
  32. 32 - Schadendorf D, Hauschild A, Ugurel S, Thoelke A, Egberts F, Kreissig M, et al. Dose-intensified bi-weekly temozolomide in patients with asymptomatic brain metastases from malignant melanoma: a phase II DeCOG/ADO study. Ann Oncol 2006 Oct;17(10):1592-7.
  33. 33 - Herfarth KK, Izwekowa O, Thilmann C, Pirzkall A, Delorme S, Hofmann U, et al. Linac-based radiosurgery of cerebral melanoma metastases. Analysis of 122 metastases treated in 64 patients. Strahlenther Onkol 2003 Jun;179(6):366-71.
  34. 34 - Hassaneen W, Hatiboglu MA, Chowdhury S, Sawaya R. Asymptomatic cerebellopontine angle and lateral ventricle metastases from renal cell carcinoma: case report and literature review. J Neurooncol 2009 Jan;91(1):101-6.
  35. 35 - Agarwala SS, Kirkwood JM, Gore M, Dreno B, Thatcher N, Czarnetski B, et al. Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. J Clin Oncol 2004 Jun 1;22(11):2101-7.

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.