Question

In which cases is histological verification of an abnormality suspected to be brain metastasis necessary?

• after which time interval between metachronous presentation of brain metastases and prior primary or metastatic tumour activity?

 

Recommendation

The guideline development group recommends conducting optimal clinical and radiological diagnostics with respect to extracranial disease activity in case of suspected brain metastasis.

Histological verification of suspected brain metastases in the case of a known primary tumour is recommended in the following situations:

  • atypical neuroradiological findings; this includes the occurrence of multiple abnormalities in immunocompromised patients in whom the possibility of brain abscesses cannot be ruled out;
  • metachronous (during the course of the disease) presentation of intracerebral abnormalities in patients with a known primary tumour that is under control, and who do not exhibit active metastasis elsewhere in the body; an interval >2 years (in the case of lung carcinoma) or >5 years (in the case of another malignancy) between the primary diagnosis and the occurrence of intracerebral abnormalities.
  • metachronous presentation of a dural abnormality that cannot be distinguished from a primary tumour such as a meningioma.

Histological verification of suspected brain metastases in the case of a known primary tumour is not recommended in the following situations:

  • in case the result will not have therapeutic consequences
  • in case of multiple abnormalities in patients with suspected brain metastases
  • in case of metachronous presentation of a solitary abnormality in the brain alongside active metastatic activity elsewhere in the body (i.e. metastases diagnosed during follow-up, in contrast to synchronous metastases, which are diagnosed together with the primary tumour)

Conclusions

Level 4
The guideline development group is of the opinion that the following circumstances render the possibility less likely that cerebral abnormalities are induced by brain metastasis of the known primary tumour:

    • solitary abnormality
    • atypical neuroradiological aspect
    • early stage of malignancy (excluding lung carcinoma)
    • a long time interval (>2 years for lung carcinoma and >5 years for other tumours) between diagnosis and the occurrence of intracerebral abnormalities
    • absence of extracranial metastases

Literature summary

Cerebral lesions in patients with suspected brain metastases may present in various ways and under different circumstances. Most often, multiple lesions are found. Abnormalities are usually detected on the basis of neurological symptoms, but may also be asymptomatic, in which case they are detected during screening or tests/examinations conducted for other reasons. Histological verification may not always be necessary, for instance in those cases where the result will not entail therapeutic consequences.

No studies have been published on the value of biopsy in patients with suspected brain metastases. In practice, the following factors are considered in deciding whether or not to obtain histological verification:

  • Solitary versus multiple lesions
  • The neuroradiological aspect
  • Whether the occurrence of brain metastases is consistent with the (expected) course of the known malignancy in a particular patient. This is related to:
    • the stage of the malignancy at the time of diagnosis
    • the interval between diagnosis and occurrence of the abnormalities in the brain. Studies have indicated that 97% of brain metastases deriving from a lung carcinoma occur within 2 years after diagnosis; in other primary tumours (breast carcinoma, colorectal carcinoma, renal carcinoma and melanoma), 45% occur within 2 years and 92% within 5 years (Schouten, 2002 (1))
    • the presence or absence of extracranial metastases
  • The therapeutic consequences associated with the result (which should be considered while taking account of the patient's physical condition, life expectancy and preferences).

References

  1. 1 - Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 2002 May 15;94(10):2698-705.

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

Initiative : 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

Objective

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.

Users

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

 

Members of the guideline panel

2011:

Chair:

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.
   

Lid

Firma

Activiteit

Overig

Dr. L.V. Beerepoot

Pfizer

Merck

Cephalon

consultatie / advisering

congres

congres

congres

Dr. W. Boogerd

Mundipharma

 

congres

Dr. M. van Dijk

Schering Plough

 

congres

Dr. A.C. Dingemans

Roche

 

Lilly

Astra Zeneca

 

Glaxo

consultatie / advisering / wetenschappelijk onderzoek

consultatie / advisering

consultatie / advisering / wetenschappelijk onderzoek

consultatie / advisering / wetenschappelijk onderzoek

congres

 

cursus

Dr. C.A. van Es

Elektra

 

congres

Dr. A. de Graeff

 

Nycomed

Wyeth

consultatie / advisering

consultatie / advisering

 

Dr. P.A.M. Hofman

Strijker NL B.V.

Medtronics Spinal

Bayer Health Care

Johnson & Johnson

 

congres

congres

congres

congres

Dr. H.F.M. van der Heijden

Astra Zeneca

Sanofi Aventis

Lilly

 

Roche

consultatie / advisering

consultatie / advisering

consultatie / advisering / wetenschappelijk onderzoek

 

congres

congres

congres

 

congres

Dr. R.L.H. Jansen

Pfizer

Roche

Sanofi Aventis

Diverse firma's

 

 

wetenschappelijk onderzoek

studies

congres

congres

congres

Dr. F.J. Lagerwaard

Roche Nederland

Roche NL-longadviesraad

Brain Lab

Varian Medical Systems

wetenschappelijk onderzoek

consultatie / advisering

 

 

 

congres

congres

   

Method of development

Evidence based

Implementation

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 http://www.oncoline.nl/. 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.